WO2025064339A1 - Compositions and methods for optimized peptide vaccines - Google Patents
Compositions and methods for optimized peptide vaccines Download PDFInfo
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- WO2025064339A1 WO2025064339A1 PCT/US2024/046867 US2024046867W WO2025064339A1 WO 2025064339 A1 WO2025064339 A1 WO 2025064339A1 US 2024046867 W US2024046867 W US 2024046867W WO 2025064339 A1 WO2025064339 A1 WO 2025064339A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001148—Regulators of development
- A61K39/00115—Apoptosis related proteins, e.g. survivin or livin
- A61K39/001151—Apoptosis related proteins, e.g. survivin or livin p53
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001154—Enzymes
- A61K39/001164—GTPases, e.g. Ras or Rho
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/82—Translation products from oncogenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4746—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used p53
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70539—MHC-molecules, e.g. HLA-molecules
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- C12N9/1205—Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/01—Phosphotransferases with an alcohol group as acceptor (2.7.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y306/00—Hydrolases acting on acid anhydrides (3.6)
- C12Y306/05—Hydrolases acting on acid anhydrides (3.6) acting on GTP; involved in cellular and subcellular movement (3.6.5)
- C12Y306/05002—Small monomeric GTPase (3.6.5.2)
Definitions
- the present invention relates generally to compositions, systems, and methods of peptide vaccines. More particularly, the present invention relates to compositions, systems, and methods of designing peptide vaccines to treat or prevent disease optimized based on predicted population immunogenicity.
- BACKGROUND [0006] The goal of a peptide vaccine is to train the immune system to recognize and expand its capacity to engage cells that display target peptides to improve the immune response to cancerous cells or pathogens.
- a peptide vaccine can also be administered to someone who is already diseased to increase their immune response to a causal cancer, other diseases, or pathogen.
- a peptide vaccine can be administered to induce the immune system to - 1 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 have therapeutic tolerance to one or more peptides.
- compositions, systems, and methods of peptide vaccines based on prediction of the target peptides that will be displayed to protect a host from cancer, other disease, or pathogen infection.
- the invention provides for a composition comprising one or more polynucleotides encoding at least two amino acid sequences, wherein the at least two amino acid sequences are selected from the group consisting of SEQ ID NOs: 17 to 176, and SEQ ID NOs: 178 to 184.
- the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides.
- an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject.
- the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele.
- each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a CTNNB1 protein.
- the fragment of the CTNNB1 protein comprises a mutation selected from the group consisting of CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, and CTNNB1 T41I.
- the invention provides for a method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein.
- the composition is an immunogenic composition.
- the at least two amino acid sequences are SEQ ID NOs: 103 and 104.
- the invention provides for composition comprising one or more polynucleotides encoding at least two amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 207 and SEQ ID NOs: 209 to 222.
- the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least - 2 - ActiveUS 205953775 Attorney Docket No.
- an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject.
- the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele.
- each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a KRAS protein.
- the invention provides for a method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein.
- the composition is an immunogenic composition.
- the one or more peptides is a modified or unmodified fragment of a protein, wherein the protein comprises a mutation selected from the group consisting of BRAF G466V, CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, CTNNB1 T41I, KRAS A146T, KRAS A146V, KRAS Q61H, PIK3CA C420R, PIK3CA E453K, PIK3CA E545A, PIK3CA E726K, PIK3CA G118D, PIK3CA H1047L, PIK3CA N345K, PIK3CA Q546K, PIK3CA Q546R, PIK3CA R108H, TP53 C176F,
- the composition is administered in an effective amount to a subject to prevent cancer. In some embodiments, the composition is administered in an effective amount to a subject to treat cancer. In some embodiments, the cancer is selected from the group consisting of pancreas, colon, rectum, kidney, bronchus, lung, uterus, cervix, bladder, liver, stomach, brain, breast, ovary, thyroid, and skin.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 17 to 184.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 17 to 184.
- the one or more peptides is a modified or unmodified fragment of a mutated CTNNB1 protein.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 222.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 222. [0032] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 185 to 222. [0033] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 185 to 222.
- the one or more peptides is a modified or unmodified fragment of a mutated KRAS protein.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 223 to 386.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 223 to 386.
- the invention provides for a peptide composition
- a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 223 to 386.
- - 7 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 223 to 386.
- the one or more peptides is a modified or unmodified fragment of a mutated PIK3CA protein.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 794.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 794.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 387 to 794.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 387 to 794.
- the one or more peptides is a modified or unmodified fragment of a mutated TP53 protein.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 16.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a BRAF G466V protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 16.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1 to 16.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1 to 16.
- the peptide composition comprises a peptide derived from a BRAF G466V protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 17 to 36. - 8 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0047]
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 D32G protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 17 to 36.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 17 to 36.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 17 to 36.
- the peptide composition comprises a peptide derived from a CTNNB1 D32G protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 37 to 52.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 68 to 86.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S33F protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 68 to 86.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 68 to 86.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 68 to 86. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S33F protein mutation. [0062] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 87 to 102. [0063] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S37C protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 87 to 102.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 87 to 102.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 87 to 102.
- the peptide composition comprises a peptide derived from a CTNNB1 S37C protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 103 to 119. - 10 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0067]
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S37F protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 103 to 119.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 103 to 119.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 103 to 119.
- the peptide composition comprises a peptide derived from a CTNNB1 S37F protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 120 to 134.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S45F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 120 to 134. [0072] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 120 to 134. [0073] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 120 to 134.
- the peptide composition comprises a peptide derived from a CTNNB1 S45F protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 135 to 150.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S45P protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 135 to 150.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 135 to 150. - 11 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0077]
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 135 to 150.
- the peptide composition comprises a peptide derived from a CTNNB1 S45P protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 151 to 167.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 T41A protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 151 to 167.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 151 to 167.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 151 to 167. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 T41A protein mutation. [0082] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 168 to 184. [0083] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 T41I protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 168 to 184.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 168 to 184.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 168 to 184.
- the peptide composition comprises a peptide derived from a CTNNB1 T41I protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 193.
- a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 193.
- - 12 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS A146T protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 193.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 185 to 193.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 185 to 193.
- the peptide composition comprises a peptide derived from a KRAS A146T protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 194 to 202.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS A146V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 194 to 202. [0092] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 194 to 202. [0093] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 194 to 202.
- the invention provides for a peptide composition
- a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 203 to 222.
- - 13 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 203 to 222.
- the peptide composition comprises a peptide derived from a KRAS Q61H protein mutation.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 223 to 239. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA C420R protein mutation. [0102] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 240 to 255. [0103] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E453K protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 240 to 255.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 240 to 255.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 240 to 255.
- the peptide composition comprises a peptide derived from a PIK3CA E453K protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 256 to 271.
- a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 256 to 271.
- - 14 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E545A protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 256 to 271.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 256 to 271.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 256 to 271.
- the peptide composition comprises a peptide derived from a PIK3CA E545A protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 272 to 290.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E726K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 272 to 290. [0112] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 272 to 290. [0113] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 272 to 290.
- the peptide composition comprises a peptide derived from a PIK3CA E726K protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 291 to 307.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA G118D protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 291 to 307.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 291 to 307. - 15 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0117]
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 291 to 307.
- the peptide composition comprises a peptide derived from a PIK3CA G118D protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 308 to 325.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA H1047L protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 308 to 325.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 308 to 325.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 308 to 325. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA H1047L protein mutation. [0122] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 326 to 339. [0123] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA N345K protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 326 to 339.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 326 to 339.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 326 to 339.
- the peptide composition comprises a peptide derived from a PIK3CA N345K protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 340 to 358. - 16 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0127]
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA Q546K protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 340 to 358.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 340 to 358.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 340 to 358.
- the peptide composition comprises a peptide derived from a PIK3CA Q546K protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 359 to 376.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA Q546R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 359 to 376. [0132] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 359 to 376. [0133] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 359 to 376.
- the peptide composition comprises a peptide derived from a PIK3CA Q546R protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 377 to 386.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA R108H protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 377 to 386.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 377 to 386. - 17 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0137]
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 377 to 386.
- the peptide composition comprises a peptide derived from a PIK3CA R108H protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 403. [0139] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C176F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 403. [0140] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 387 to 403.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 387 to 403. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C176F protein mutation. [0142] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 404 to 420. [0143] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C176Y protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 404 to 420.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 404 to 420.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 404 to 420.
- the peptide composition comprises a peptide derived from a TP53 C176Y protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 421 to 440. - 18 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0147]
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C238Y protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 421 to 440.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 421 to 440.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 421 to 440.
- the peptide composition comprises a peptide derived from a TP53 C238Y protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 441 to 457.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C275Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 441 to 457. [0152] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 441 to 457. [0153] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 441 to 457.
- the peptide composition comprises a peptide derived from a TP53 C275Y protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 458 to 473.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 E285K protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 458 to 473.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 886 to 895. - 33 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0289]
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S37F protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 886 to 895.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 886 to 895.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 886 to 895.
- the peptide composition comprises a peptide derived from a CTNNB1 S37F protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 896 to 905.
- the peptide composition comprises a peptide derived from a CTNNB1 S45F protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 906 to 915.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S45P protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 906 to 915.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 906 to 915.
- a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 906 to 915.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 906 to 915.
- the peptide composition comprises a peptide derived from a CTNNB1 S45P protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 916 to 925.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 T41A protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 916 to 925.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 916 to 925.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 936 to 945. - 35 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0309]
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS A146T protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 936 to 945.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS A146V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 946 to 955. [0314] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 946 to 955. [0315] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 946 to 955.
- the peptide composition comprises a peptide derived from a KRAS A146V protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 956 to 965.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS Q61H protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 956 to 965.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 966 to 975.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA C420R protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 966 to 975.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 966 to 975.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 966 to 975. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA C420R protein mutation. [0324] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 976 to 985. [0325] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E453K protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 986 to 995. - 37 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0329]
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E545A protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 986 to 995.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E726K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 996 to 1005. [0334] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 996 to 1005. [0335] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 996 to 1005.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1016 to 1025. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA H1047L protein mutation. [0344] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1026 to 1035. [0345] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA N345K protein mutation.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA Q546R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1046 to 1055. [0354] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1046 to 1055. [0355] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1046 to 1055.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1056 to 1065. - 40 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0359]
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1056 to 1065.
- the peptide composition comprises a peptide derived from a PIK3CA R108H protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1076 to 1085.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1076 to 1085.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1076 to 1085.
- the peptide composition comprises a peptide derived from a TP53 C176Y protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1086 to 1095. - 41 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0369]
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C238Y protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1086 to 1095.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1086 to 1095.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1086 to 1095.
- the peptide composition comprises a peptide derived from a TP53 C238Y protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1096 to 1105.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C275Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1096 to 1105. [0374] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1096 to 1105. [0375] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1096 to 1105.
- the peptide composition comprises a peptide derived from a TP53 C275Y protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1106 to 1115.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 G245S protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1106 to 1115.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1106 to 1115. - 42 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0379]
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1106 to 1115.
- the peptide composition comprises a peptide derived from a TP53 G245S protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1116 to 1125.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 G245V protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1116 to 1125.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1116 to 1125.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1116 to 1125. In some embodiments, the peptide composition comprises a peptide derived from a TP53 G245V protein mutation. [0384] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1126 to 1135. [0385] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 H179Y protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1136 to 1145.
- a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1136 to 1145.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 H193R protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1136 to 1145.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1136 to 1145.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1136 to 1145.
- the peptide composition comprises a peptide derived from a TP53 H193R protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1146 to 1155.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 I195T protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1146 to 1155. [0394] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1146 to 1155. [0395] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1146 to 1155.
- the peptide composition comprises a peptide derived from a TP53 I195T protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1156 to 1165.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 K132E protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1156 to 1165.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1156 to 1165. - 44 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0399]
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1156 to 1165.
- the peptide composition comprises a peptide derived from a TP53 K132E protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1166 to 1175.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 K132N protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1166 to 1175.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1166 to 1175.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1166 to 1175. In some embodiments, the peptide composition comprises a peptide derived from a TP53 K132N protein mutation. [0404] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1176 to 1185. [0405] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 P151S protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1176 to 1185.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1176 to 1185.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1176 to 1185.
- the peptide composition comprises a peptide derived from a TP53 P151S protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1186 to 1195. - 45 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0409]
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R213L protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1186 to 1195.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1186 to 1195.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1186 to 1195.
- the peptide composition comprises a peptide derived from a TP53 R213L protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1196 to 1205.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R249M protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1196 to 1205. [0414] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1196 to 1205. [0415] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1196 to 1205.
- the peptide composition comprises a peptide derived from a TP53 R249M protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1206 to 1215.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R249S protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1206 to 1215.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1206 to 1215. - 46 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0419]
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1206 to 1215.
- the peptide composition comprises a peptide derived from a TP53 R249S protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1216 to 1225.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R273L protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1216 to 1225.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1216 to 1225.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1216 to 1225. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R273L protein mutation. [0424] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1226 to 1235. [0425] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 S127Y protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1226 to 1235.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1226 to 1235.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1226 to 1235.
- the peptide composition comprises a peptide derived from a TP53 S127Y protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1236 to 1245. - 47 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0429]
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 S241F protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1236 to 1245.
- the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1236 to 1245.
- the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1236 to 1245.
- the peptide composition comprises a peptide derived from a TP53 S241F protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1246 to 1255.
- the peptide composition comprises a peptide derived from a TP53 V157F protein mutation.
- the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1256 to 1259.
- the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 V272M protein mutation.
- the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1256 to 1259.
- the one or more HLA alleles is selected from the group consisting of DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10301, DPA10103-DPB10401, DPA10103-DPB10402, DPA10103- DPB10501, DPA10103-DPB10601, DPA10103-DPB11001, DPA10103-DPB110501, DPA10103-DPB11101, DPA10103-DPB112401, DPA10103-DPB112601, DPA10103- - 56 - ActiveUS 205953775 Attorney Docket No.
- the one or more HLA alleles is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A0301, A0302, A0305, A1101, A1102, A2301, A2402, A2403, A2407, A2410, A2464, A2501, A2601, A2603, A2608, A2612, A2630, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3101, A3104, A3201, A3301, A3303, A3305, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A6802, A6827, A6901, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407,
- a method for formulating a composition (e.g., a vaccine), the method comprising determining that a subject in need thereof of the composition expresses one or more HLA alleles, and formulating the composition by selecting nucleic acid sequences - 63 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 encoding for one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 61281.
- the one or more HLA alleles is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A0301, A0302, A0305, A1101, A1102, A2301, A2402, A2403, A2407, A2410, A2464, A2501, A2601, A2603, A2608, A2612, A2630, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3101, A3104, A3201, A3301, A3303, A3305, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A6802, A6827, A6901, A74, A7401, A7402, A7403, A7404, A7405, A7406,
- FIG.1 is a flow chart of a vaccine optimization method.
- FIG.2 is a flow chart of a vaccine optimization method with seed set compression.
- FIG.3 shows the predicted population coverage for MHC class I vaccines for single mutations in cancer-related genes. Each row describes the coverage of a vaccine for a single mutation in one of the BRAF, CTNNB1, KRAS, PIK3CA, and TP53 genes.
- FIG.4 shows the predicted population coverage for MHC class II vaccines for single mutations in cancer-related genes.
- Each row describes the coverage of a vaccine for a single mutation in one of the BRAF, CTNNB1, KRAS, PIK3CA, and TP53 genes.
- the columns describe the predicted population coverage of each vaccine for a specific gene mutation (e.g., BRAF G466V) at varying number of peptides in the vaccine as annotated at the top of the column.
- FIG.5 shows predicated peptide-HLA hits by vaccine size for a KRAS G12V vaccine for the HLA diplotype HLA-A02:03, HLA-A11:01, HLA-B55:02, HLA-B58:01, HLA- C03:02, HLA-C03:03.
- FIG.6 is a table showing the respective probabilities of target presentations for various mutated protein targets across different cancers.
- FIG.7 is a flow chart showing a multiple target (combined) vaccine optimization method.
- FIG.8 shows an example Python implementation of the MERGEMULTI function for combined vaccine design procedures.
- DETAILED DESCRIPTION [0474] The practice of the embodiments disclosed herein can employ, unless otherwise indicated, conventional techniques of genetics, molecular biology, protein chemistry, computational biology, and formulation science. [0475] All references cited in this disclosure are hereby incorporated by reference in their entireties. In addition, any manufacturers’ instructions or catalogues for any products cited or mentioned herein are incorporated by reference. Documents incorporated by reference into this text, or any teachings therein, can be used in the practice of the present invention. Documents incorporated by reference into this text are not admitted to be prior art. Definitions [0476] The following are definitions of terms used in the present specification.
- peptide means a chain of amino acids of any length, for example, an amino acid polymer.
- the peptide can be linear or branched, can comprise modified amino acids, and can be interrupted by non-amino acids.
- composition is meant to encompass, and is not limited to, pharmaceutical compositions and nutraceutical compositions, such as a vaccine, containing drug substance (e.g., nucleic acids or peptides).
- the composition may also contain one or more excipients that are inactive ingredients or compounds devoid of pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of a human.
- the terms “immunogenic composition,” and “immunogenic peptide composition,” mean a composition that can induce an immune response (e.g., an adaptive immune response) in a subject, unless clearly indicated otherwise.
- the “immunogenic composition” or the “immunogenic peptide composition” is a vaccine composition.
- the “immunogenic composition” or the “immunogenic peptide composition” can generate acquired immunity against a pathogen or disease in a subject.
- the acquired immunity does not prevent the disease in the subject but reduces its severity.
- the “immunogenic composition” or the “immunogenic peptide composition” (e.g., a vaccine) promotes immune system tolerance for one or more proteins.
- the term “therapeutically effective amount” or “effective amount” refers to any amount that is necessary or sufficient for achieving or promoting a desired outcome. In some instances, “an effective amount” is a therapeutically effective amount. A “therapeutically effective amount” is any amount that is necessary or sufficient for promoting or achieving a desired biological response in a subject.
- the “effective amount” for any particular application can vary depending on such factors as the disease or condition being treated or intended to be prevented, the particular agent being administered, the size/weight of the subject, or the severity - 68 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of the disease or condition to be treated or prevented.
- One of ordinary skill in the art can empirically determine the effective amount of a particular agent without necessitating undue experimentation.
- the terms “subject” and “patient” are used interchangeably herein.
- subject refers to an animal, preferably a mammal including a nonprimate and a primate (e.g., a monkey such as a cynomolgus monkey, a chimpanzee, and a human), and a human.
- a primate e.g., a monkey such as a cynomolgus monkey, a chimpanzee, and a human
- animal also includes, but is not limited to, companion animals such as cats and dogs; zoo animals; wild animals; farm or sport animals such as ruminants, non-ruminants, livestock and fowl (e.g., horses, cattle, sheep, pigs, turkeys, ducks, and chickens); and laboratory animals, such as rodents (e.g., mice, rats), rabbits; and guinea pigs, as well as animals that are cloned or modified, either genetically or otherwise (e.g., transgenic animals).
- the term “subject” or “patient” refers to a human.
- treating refers to the attempted reduction or amelioration of the progression, severity and/or duration of a disorder, or the attempted amelioration of one or more symptoms thereof resulting from the administration of one or more modalities (e.g., one or more vaccines or therapeutic agents such as a composition described herein).
- a subject is successfully “treated” for a disease or disorder if the patient shows total, partial, or transient alleviation or elimination of at least one symptom or measurable physical parameter associated with the disease or disorder.
- the terms “prevent,” “preventing,” “prevention,” “alleviate,” or “alleviating” refer to the prevention, inhibition, or lessening of the recurrence, onset, or development of a disorder or a symptom thereof in a subject resulting from the administration of a therapy (e.g., a vaccine), or the administration of a combination of therapies (e.g., a combination of vaccine(s) and/or therapeutic agents).
- a therapy e.g., a vaccine
- a combination of therapies e.g., a combination of vaccine(s) and/or therapeutic agents.
- Numeric ranges are inclusive of the numbers defining the range, and any individual value provided herein can serve as an endpoint for a range that includes other individual values provided herein.
- a set of values such as 1, 2, 3, 8, 9, and 10 is also a disclosure of a range of numbers from 1-10, from 1-8, from 3-9, and so forth.
- a disclosed range is a disclosure of each individual value (i.e., intermediate) encompassed by the range, including integers and fractions.
- a stated range of 5-10 is also a disclosure of 5, 6, 7, 8, 9, and 10 individually, and of 5.2, 7.5, 8.7, and so forth.
- - 69 - ActiveUS 205953775 Attorney Docket No.
- compositions e.g., vaccines
- MHC Major Histocompatibility Complex
- HLA HLA
- compositions e.g., vaccines
- compositions that incorporate peptide sequences that will be displayed by MHC molecules on cells to induce therapeutic tolerance in antigen-specific immunotherapy for autoimmune diseases (Alhadj Ali et al., 2017, Gibson, et al.2015).
- a composition (e.g., a vaccine) comprises one or more peptides.
- a composition (e.g., a vaccine) includes an RNA (e.g., mRNA) or DNA construct administered for expression in vivo that encodes for one or more peptides.
- RNA e.g., mRNA
- the immunogenic compositions and methods described herein are applicable for designing and preparing a broad range of compositions including vaccine compositions.
- the term peptide-HLA binding is defined to be the binding of a peptide to an HLA allele, and can either be computationally predicted, experimentally observed, or computationally predicted using experimental observations.
- the metric or score of peptide-HLA binding can be expressed as affinity (for example, based on the equilibrium dissociation constant (KD), measured in molar units (M)), percentile rank, binary at a predetermined threshold, probability, rate of disassociation, or other metrics as are known in the art.
- affinity for example, based on the equilibrium dissociation constant (KD), measured in molar units (M)
- M molar units
- percentile rank binary at a predetermined threshold
- probability rate of disassociation
- the metric or score of peptide-HLA display can be expressed as affinity (for example, based on the equilibrium dissociation constant (KD), measured in molar units (M)), percentile rank, binary at a predetermined threshold, probability, or other metrics as are known in the art.
- metrics of peptide-HLA binding are used for metrics of peptide-HLA display since peptide-HLA display depends upon peptide-HLA binding.
- the term peptide-HLA immunogenicity metric is defined as the activation of T cells based upon their recognition of a peptide when bound by an HLA allele.
- peptide-HLA immunogenicity score is another term for a peptide-HLA immunogenicity metric, and the terms are interchangeable.
- a peptide-HLA immunogenicity metric can vary from individual to individual, and the metric for peptide-HLA immunogenicity can be expressed as a probability, a - 70 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 binary indicator, or other metric that relates to the likelihood that a peptide-HLA combination will be immunogenic.
- peptide-HLA immunogenicity is defined as the induction of immune tolerance based upon the recognition of a peptide when bound by an HLA allele.
- a peptide-HLA immunogenicity metric can be computationally predicted, experimentally observed, or computationally predicted using experimental observations.
- a peptide-HLA immunogenicity metric is based only upon peptide-HLA binding, since peptide-HLA binding is necessary for peptide-HLA immunogenicity.
- peptide-HLA immunogenicity data or computational predictions of peptide-HLA immunogenicity can be included and combined with scores for peptide binding or peptide display in the methods disclosed herein.
- One way of combining the scores is using immunogenicity data for peptides assayed for immunogenicity in diseased or vaccinated individuals and assigning peptides to the HLA allele that displayed them in the individual by choosing the HLA allele that computational methods predict has the highest likelihood of display.
- computational predictions of binding can be used for peptides that are not experimentally assayed.
- different computational methods of predicting peptide-HLA immunogenicity or peptide-HLA binding can be combined (Liu et al., 2020b).
- peptide-HLA hits is the number of unique combinations of peptides and HLA alleles that exhibit peptide-HLA immunogenicity or binding at a predetermined threshold.
- a peptide-HLA hit of 2 can mean that one peptide is predicted to be bound (or trigger T cell activation) by two different HLA alleles, two peptides are predicted to be bound (or trigger T cell activation) by two different HLA alleles, or two peptides are predicted to be bound (or trigger T cell activation) by the same HLA allele.
- the expected number of peptide-HLA hits is the average number of peptide-HLA hits in each set of HLAs that represent an individual, weighted by their frequency of occurrence.
- Peptide display by an MHC molecule is necessary, but not sufficient, for a peptide to be immunogenic and cause the recognition of the resulting peptide-MHC complex by an individual’s T cells to trigger T cell activation, expansion, and immune memory.
- ELISPOT Singlex Identification of Antigen-Specific T Cell Receptors Using a Combination of Immune Assays and Immune Receptor Sequencing (MIRA) assay (Klinger et al., 2015) are used to score peptide display or affinity (e.g., a peptide immunogenicity that requires peptide binding) by an MHC molecule (e.g., HLA allele, measured as a peptide-HLA binding score).
- MIRA Immune Receptor Sequencing
- experimental data from assays such as the ELISPOT (Slota et al., 2011) or the MIRA assay can be combined with machine learning based predictions for scoring peptide display by an MHC molecule or peptide binding (e.g., binding affinity) by an MHC molecule (e.g., HLA allele, measured as a peptide-HLA binding score) for determining a peptide-HLA immunogenicity metric.
- the MHCflurry or NetMHCpan (Reynisson et al., 2020) computational methods are used to predict MHC class I display of a peptide by an HLA allele.
- a composition (e.g., an immunogenic composition) includes nucleic acids sequences encoding for one or more peptides, wherein the one or more peptides is MHC restricted (also referred to as HLA restricted).
- a composition (e.g., an immunogenic composition) includes one or more peptides, wherein the one or more peptides is MHC restricted (also referred to as HLA restricted).
- an MHC restriction of a peptide sequence refers to the presence of an MHC (or HLA) allele in a subject that allows for peptide-HLA display, peptide-HLA binding, or peptide-HLA immunogenicity for the peptide.
- An HLA allele is abbreviated by its locus, its two digit allele group, and its two or three digit specific HLA protein.
- the HLA allele HLA-A*02:01 is abbreviated as A0201.
- MHC Class II alleles that begin with DP, DQ, or DR, the first digit is part of the locus, followed by a two or three digit allele group and a two or three digit specific HLA protein.
- a composition is designed based on MHC restrictions such that one or more peptides (or nucleic acids encoding for one or more peptides) is included in the composition based on a determination that one or more MHC (or HLA) alleles is present in a subject in need thereof of the composition.
- the MHC (or HLA) alleles present in the subject are determined to allow for display or immunogenicity (peptide-HLA display or peptide-HLA immunogenicity) of the one or more peptides (or nucleic acids encoding for one or more peptides) in the composition.
- the HLA alleles present or expressed in a subject are used to select one or more peptides (or nucleic acids encoding the peptides) for inclusion in a composition to be administered to the subject.
- the selection is based on the likelihood that a given HLA allele expressed in the - 72 - ActiveUS 205953775 Attorney Docket No.
- a composition is designed based on MHC restrictions such that one or more peptides (or nucleic acids encoding for one or more peptides) is included in the composition based on a determination of the MHC (or HLA) alleles present in a desired population of people.
- MHC or HLA
- Population based HLA allele frequencies can be determined from the Allele Frequency Net Database, the HLA haplotype frequencies provided in Liu et al., Cell Systems 11, Issue 2, p.131-146 (Liu et al., 2020a), or other sources known in the art.
- OptiVax are used for peptide selection using population HLA frequencies (Liu et al., 2020a, Liu et al., 2022).
- a given peptide sequence can have more than one MHC restriction.
- SEQ ID NO: 16 has an MHC restriction that includes an HLA allele selected from the group consisting of A3201, B1517, and B1525.
- a peptide (or nucleic acid sequences encoding for the peptide) is included in a composition only if two or more MHC (or HLA) alleles are present the subject that are also in the MHC restriction of the peptide.
- the peptide (or nucleic acid sequences encoding for the peptide) containing SEQ ID NO: 16 is included in the composition only if a subject has both A3201 and B1517 alleles.
- MHC restrictions can be based on both MHC class I and MHC class II alleles.
- the one or more amino acid sequences is selected for inclusion in a composition (e.g., a vaccine) based on an MHC restriction that includes an HLA allele described in the notes field of the respective SEQ ID NO entry in the sequence listing.
- SEQ ID NO: 16 has a note filed that states: “HLAs: A3201 B1517 B1525.”
- SEQ ID NO:16 is included in the composition if it is determined that an individual in need thereof of the composition expresses one or more of the HLA alleles selected from the group consisting of A3201, B1517, and B1525.
- Other sequences listed in the sequence listing are considered for inclusion in a composition based on their corresponding HLA alleles as listed in their respective notes field.
- the one or more amino acid sequences is selected for inclusion in the MHC class II peptide vaccine based on an MHC restriction that includes an HLA allele described in the notes field of the respective SEQ ID NO entry in the sequence listing.
- SEQ ID NO: 835 has an MHC restriction that includes an HLA allele selected from the group consisting of DRB1_0101, DRB1_0701, DRB1_0901, DRB1_1001, DPA10103-DPB10601, DPA10103-DPB15001, DPA10105-DPB15001, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401- DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401.
- NetMHCpan-4.1 and NetMHCIIpan-4.0 utilize the NNAlign_MA algorithm (Alvarez et al., 2019, incorporated by reference in its entirety herein) for predicting peptide-HLA binding.
- NNAlign_MA is in turn based upon the NNAlign (Nielsen et al., 2009, Nielsen et al., 2017, incorporated by reference in their entireties herein) neural network.
- NetMHCpan-4.1 consists of at least 567,000 parameters that must be evaluated with at least 567,000 arithmetic operations for computing peptide-MHC binding.
- Each network architecture (2, 10, 20, 40, or 60 hidden neurons) is trained with 10 different random parameter initializations and 5-fold cross- validation resulting in a total of 250 individual trained networks (5 architectures x 10 initializations x 5 cross-validation).
- These 250 trained networks are used as an ensemble with 50 networks having at least 360 parameters (180 inputs x 2 neurons), 50 networks having at least 1800 parameters (180 inputs x 10 neurons), 50 networks having at least 3600 parameters (180 inputs x 20 neurons), 50 networks having at least 7200 parameters (180 inputs x 40 neurons), and 50 networks having at least 10,800 parameters (180 inputs x 60 neurons).
- the ensemble of 250 networks in NetMHCIIpan-4.0 consists of at least 1,188,000 parameters that must be evaluated with at least 1,188,000 arithmetic operations for computing peptide-MHC binding.
- computational methods used to predict either MHC class I (e.g., MHCflurry, NetMHCpan) or class II (e.g., NetMHCIIpan) peptide-HLA binding scores or peptide-HLA immunogenicity metrics are based upon data from experimental mass spectrometry observations of peptides bound by MHC molecules.
- computational methods used to predict either MHC class I (e.g., MHCflurry, NetMHCpan) or class II (e.g., NetMHCIIpan) peptide-HLA binding scores or peptide-HLA immunogenicity metrics are based upon data from experimental observations of peptide-MHC binding affinity.
- experimental observations of peptide-MHC binding affinity or immunogenicity including mass spectrometry measurements of peptide-HLA binding and measurements of T cell activation, can be found in databases such as the Immune Epitope Database (IEDB) (Vita et al., 2018).
- IEDB Immune Epitope Database
- MHCflurry 2.0 (O’Donnell et al., 2020, incorporated by reference in its entirety herein) is based upon 493,473 mass spectrometry measurements of peptide-HLA binding, and 219,596 affinity measurements of peptide-HLA - 75 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 binding.
- the output of NetMHCpan-4.1 (Reynisson et al., 2020) is based upon 665,492 mass spectrometry measurements of peptide-HLA binding, and 52,402 affinity measurements of peptide-HLA binding.
- a peptide is displayed by an MHC molecule when it binds within the groove of the MHC molecule and is transported to the cell surface where it can be recognized by a T cell receptor.
- a target peptide refers to a foreign peptide or a self-peptide.
- a peptide that is part of the normal proteome in a healthy individual is a self-peptide
- a peptide that is not part of the normal proteome is a foreign peptide.
- target peptides can be part of the normal proteome that exhibit aberrant expression (e.g., cancer-testis antigens such as NY-ESO-1).
- Foreign peptides can be generated by mutations in normal self- proteins in tumor cells that create epitopes called neoantigens, or by pathogenic infections.
- a neoantigen is any subsequence of a human protein, where the subsequence contains one or more altered amino acids or protein modifications that do not appear in a healthy individual.
- foreign peptide refers to an amino acid sequence encoding a fragment of a target protein/peptide (or a full-length protein/peptide), the target protein/peptide consisting of a neoantigen protein, a pathogen proteome, or any other undesired protein that is non-self and is expected to be bound and displayed by an HLA allele.
- Protein genes identified by their UniProt ID that are frequently mutated in cancer include RASK_HUMAN (also called KRAS), AKT1_HUMAN, BRAF_HUMAN, CTNB1_HUMAN (also called CTNNB1), EGFR_HUMAN, GTF2I_HUMAN, RASH_HUMAN (also called HRAS), IDHC_HUMAN (also called IDH1), RASN_HUMAN (also called NRAS), PIK3CA_HUMAN, PTEN_HUMAN, and P53_HUMAN (also called TP53).
- RASK_HUMAN also called KRAS
- AKT1_HUMAN also called AKT1_HUMAN
- BRAF_HUMAN also called CTNB1_HUMAN
- CTNB1_HUMAN also called CTNNB1
- EGFR_HUMAN also called GTF2I_HUMAN
- RASH_HUMAN also called HRAS
- IDHC_HUMAN also called IDH1
- RASN_HUMAN also called NRAS
- KRAS G12D is a mutation in the KRAS protein of position 12 from glycine to aspartic acid (G12D). Proteins may contain multiple mutations at different positions. Herein we may refer to a gene without the “_HUMAN” suffix for conciseness. [0499] KRAS gene mutations are the most frequently mutated oncogenes in cancer, but they have been very difficult to treat with small molecule therapeutics.
- the KRAS protein is part of - 76 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 a signaling pathway that controls cellular growth and point mutations in the protein can cause constitutive pathway activation and uncontrolled cell growth.
- KRAS oncogenic mutations include the mutation of position 12 from glycine to aspartic acid (G12D), glycine to valine (G12V), glycine to arginine (G12R), or glycine to cystine (G12C); or the mutation of position 13 from glycine to aspartic acid (G13D).
- the corresponding foreign peptides contain these mutations.
- KRAS is a member of the RAS family of genes that also includes HRAS and NRAS. KRAS, HRAS, and NRAS have identical sequences from residue 1 to residue 86.
- a KRAS G12D vaccine is also a vaccine for HRAS G12D.
- Certain self-proteins such as cancer-testis antigens, are present in cancerous cells at aberrantly high levels and thus can be targets for vaccination to induce an intolerant T cell response against cells displaying peptides derived from these self-proteins on MHC molecules.
- cancer-related proteins by their UniProt IDs include CTG1B_HUMAN (also known as NY-ESO-1), MAGA1_HUMAN, MAGA3_HUMAN, MAGA4_HUMAN, MAGC1_HUMAN, MAGC3_HUMAN, SSX2_HUMAN, PRAME_HUMAN, KKLC1_HUMAN (also known as CT83), PMEL_HUMAN (as known as gp100), TYRP1_HUMAN (also known as gp75), TYRP2_HUMAN (also known as DCT), and MAR1_HUMAN.
- CTG1B_HUMAN also known as NY-ESO-1
- MAGA1_HUMAN also known as NY-ESO-1
- MAGA3_HUMAN MAGA4_HUMAN
- MAGC1_HUMAN MAGC3_HUMAN
- SSX2_HUMAN SSX2_HUMAN
- PRAME_HUMAN also known as CT83
- PMEL_HUMAN as gp100
- autoimmune disorders are caused by the loss of self-tolerance by the immune system to self-proteins and are involved in autoimmune disorders such as diabetes, multiple sclerosis, and autoimmune encephalomyelitis.
- Induction of tolerance for autoimmune-related self- peptides can be accomplished by antigen-specific tolerization using the delivery of vaccine antigens with a tolerization protocol.
- An example of a protocol for the induction of tolerance with a lipid-nanoparticle (LNP) encapsulating RNA (e.g., mRNA-LNP) vaccine is described by Krienke et al., 2021 and is incorporated by reference in its entirety herein.
- LNP lipid-nanoparticle
- autoimmune disease-related proteins include UniProt IDs INS_HUMAN (also known as insulin), and MOG_HUMAN (also known as Myelin-oligodendrocyte glycoprotein). Individuals with diabetes can suffer from a lack of tolerance to INS_HUMAN, and individuals - 77 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 with multiple sclerosis or autoimmune encephalomyelitis can suffer from a lack of tolerance to MOG_HUMAN.
- a challenge for the design of peptide vaccines is the diversity of human MHC alleles (HLA alleles) that each have specific preferences for the peptide sequences they will display.
- HLA loci located within the MHC, encode the HLA class I and class II molecules.
- An individual’s HLA type describes the alleles they carry at each of these loci.
- Peptides of length of between about 8 and about 11 residues can bind to HLA class I (or MHC class I) molecules whereas those peptides of length of between about 13 and about 25 residues bind to HLA class II (or MHC class II) molecules (Rist et al., 2013; Chicz et al., 1992).
- HLA alleles Human populations that originate from different geographies have differing frequencies of HLA alleles, and these populations exhibit linkage disequilibrium between HLA loci that result in population specific haplotype frequencies.
- methods are disclosed for creating effective vaccines that include consideration of the HLA allelic frequency in the target population, as well as linkage disequilibrium between HLA genes to achieve a set of peptides that is likely to be robustly displayed.
- the present disclosure provides for compositions, systems, and methods of vaccine designs that produce immunity to single or multiple targets.
- a target is a neoantigen protein sequence, a pathogen proteome, or any other undesired protein sequence that is non-self and is expected to be bound and displayed by an HLA molecule (also referred to herein as an HLA allele).
- HLA molecule also referred to herein as an HLA allele.
- a target may result in multiple peptide sequences that are displayed by a variety of HLA alleles.
- one method to increase the probability of vaccine efficacy is to use a diverse set of target peptides (e.g., at least two peptides) to increase the chances that some subset of them will be immunogenic in a given individual.
- target peptides e.g., at least two peptides
- Prior research using mouse models has shown that most MHC displayed peptides are immunogenic, but immunogenicity varies from individual to individual as described in Croft et al. (2019).
- experimental peptide-HLA immunogenicity data are used - 78 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 to determine which target peptides and their modifications will be effective immunogens in a vaccine.
- a target peptide’s amino acid composition can be altered to change one or more residues.
- Anchor residues are amino acids that interact with an HLA molecule and have the largest influence on the affinity of a peptide for an HLA molecule.
- Peptides with one or more altered amino acid residues are called heteroclitic peptides.
- heteroclitic peptides include target peptides with residue modifications at anchor positions.
- heteroclitic peptides include target peptides with residue modifications at non- anchor positions.
- heteroclitic peptides include target peptides with residue modifications that include unnatural amino acids and amino acid derivatives.
- Modifications to create heteroclitic peptides can improve the binding of peptides to both MHC class I and MHC class II molecules, and the modifications required can be both peptide and MHC class specific. Since peptide anchor residues face the MHC molecule groove, they are less visible than other peptide residues to T cell receptors. Thus, heteroclitic peptides with anchor residue modifications have been observed to induce a T cell response where the stimulated T cells also respond to unmodified peptides. It has been observed that the use of heteroclitic peptides in a vaccine can improve a vaccine’s effectiveness (Zirlik et al., 2006).
- the immunogenicity of heteroclitic peptides are experimentally determined and their ability to activate T cells that also recognize the corresponding base (also called seed) peptide of the heteroclitic peptide is determined, as is known in the art (Houghton et al., 2007). In some embodiments, these assays of the immunogenicity and cross-reactivity of heteroclitic peptides are performed when the heteroclitic peptides are displayed by specific HLA alleles. - 79 - ActiveUS 205953775 Attorney Docket No.
- a method for formulating peptide vaccines using a single vaccine design for one or more targets.
- a single target is a foreign protein with a specific mutation (e.g., KRAS G12D).
- a single target is a self-protein (e.g., a protein that is overexpressed in tumor cells such as cancer/testis antigens).
- a single target is a pathogen protein (e.g., a protein contained in a viral proteome).
- the method includes extracting peptides to construct a candidate set from all target proteome sequences (e.g., entire KRAS G12D protein) as described in Liu et al. (2020a).
- FIGs.1 and 2 depict flow charts, for example, vaccine design methods that can be used for MHC class I or MHC class II vaccine design.
- a Candidate Peptide Set (see FIGs.1 and 2) is comprised of target peptides extracted by windowing an input protein sequence.
- extracted target peptides are of amino acid length of between about 8 and about 10 (e.g., for MHC class I binding (Rist et al., 2013)). In some embodiments, the extracted target peptides presented by MHC class I molecules are longer than 10 amino acid residues, such as 11 residues (Trolle et al., 2016). In some embodiments, extracted target peptides are of length between about 13 and about 25 (e.g., for class II binding (Chicz et al., 1992)). In some embodiments, sliding windows of various size ranges described herein are used over the entire proteome. In some embodiments, other target peptide lengths for MHC class I and class II sliding windows can be utilized.
- computational predictions of proteasomal cleavage are used to filter or select peptides in the candidate set.
- One computational method for predicting proteasomal cleavage is described by Nielsen et al. (2005).
- peptide mutation rates, glycosylation, cleavage sites, or other criteria can be used to filter peptides as described in Liu et al. (2020a).
- peptides can be filtered based upon evolutionary sequence variation above a predetermined threshold. Evolutionary sequence variation can be computed with respect to other species, other pathogens, other pathogen strains, or other related organisms.
- a first peptide set is the candidate set.
- the next step of the method includes scoring the target peptides in the candidate set for peptide-HLA binding to all considered HLA - 80 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 alleles as described in Liu et al. (2020a) and Liu et al. (2020b).
- a first peptide set is the candidate set after scoring the target peptides. Scoring can be accomplished for human HLA molecules, mouse H-2 molecules, swine SLA molecules, or MHC molecules of any species for which prediction algorithms are available or can be developed.
- Scoring metrics can include the affinity for a target peptide to an HLA allele in nanomolar, eluted ligand, presentation, and other scores that can be expressed as percentile rank or any other metric.
- the candidate set may be further filtered to exclude peptides whose predicted binding cores do not contain a particular pathogenic or neoantigen target residue of interest or whose predicted binding cores contain the target residue in an anchor position.
- the candidate set may also be filtered for target peptides of specific lengths, such as length 9 for MHC class I, for example.
- scoring of target peptides is accomplished with experimental data or a combination of experimental data and computational prediction methods.
- a base set (also referred to as seed set herein) is constructed by selecting peptides from the scored candidate set using individual peptide-HLA binding or immunogenicity criteria (e.g., first peptide set) (FIG.1).
- the selection can be based on the peptide-HLA binding score or peptide-HLA immunogenicity metric with the best affinity or highest immunogenicity (e.g., predicted to bind the strongest or activate T cells the most for a given HLA allele).
- the criteria used for scoring peptide-HLA binding during the scoring procedure can accommodate different goals during the base set selection and vaccine design phases. For example, a target peptide with peptide-HLA binding affinities of 500 nM may be displayed by an individual that is diseased, but at a lower frequency than a target peptide with a 50 nM peptide-HLA binding affinity.
- a more constrained affinity criteria may be used (e.g., when selecting a third peptide set, the Vaccine for Target(s) in FIGs.1 and 2), such a 50 nM, to increase the probability that a vaccine peptide will be found and displayed by HLA molecules.
- a relatively less constrained threshold e.g., less than about 1000 nM or less than about 500 nM
- immunogenicity or peptide-HLA binding is used as a first threshold for filtering candidate peptide-HLA scores (the first Peptide Scoring and Score Filtering step in FIGs.1 and 2) and a relatively more constrained second threshold (e.g., less than about 50 nM) is used for filtering expanded set peptide-HLA scores (the second Peptide Filtering and Scoring step in FIGs.1 and 2) for their scores for specific HLA alleles.
- specific peptide-HLA scores are not used for modified peptides for a given HLA for vaccine design when their unmodified counterpart peptide does not pass the first less constrained threshold.
- Filtering of peptide-HLA scores can occur for any relevant metric (binding affinity, probability of binding, probability of immunogenicity, etc.). This filtering of peptide-HLA scores is based on the observation that peptides that are not immunogenic enough for vaccine inclusion may be antigenic (meet the first filtering threshold) and thus recognized by T cell clonotypes expanded by a vaccine.
- a peptide is antigenic when it is recognized by a T cell receptor and results in a response such as CD8+ T cell cytotoxicity or CD4+ cell activation.
- Derivatives of an antigenic peptide may be strongly immunogenic, included in a vaccine, and thus activate and expand T cells that recognize the antigenic peptide.
- the expansion of T cells that recognize an unmodified antigenic peptide can provide an immune response that contributes to disease control.
- the first less constrained threshold for admitting a peptide-HLA score for a peptide for an HLA allele is determined by the best peptide-HLA score of the peptide’s heteroclitic derivatives for the same HLA.
- the probability threshold for binding or immunogenicity for a first threshold for a peptide-HLA score may be lower for an HLA allele when the probability of immunogenicity or binding for the peptide’s best derivative is higher for the same HLA.
- the product (or other function) of a peptide’s peptide-HLA binding or immunogenicity probability score and the peptide-HLA binding or immunogenicity probability score for its best derivative peptide for the same HLA allele are required to meet a specified threshold (e.g., 0.5, 0.6, 0.7, 0.8, or 0.9).
- peptides are scored for third peptide set (Vaccine for Target(s) in FIGs.1 and 2) potential inclusion that have peptide-HLA binding affinities less than about 500 nM.
- peptides are selected for the base set that have peptide- HLA binding affinities less than about 1000 nM for at least one HLA allele.
- predictions of peptide-HLA immunogenicity can be used to qualify target peptides for base set inclusion.
- experimental observations of the immunogenicity of peptides in the context of their display by HLA alleles or experimental observation of the binding of - 82 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 peptides to HLA alleles can be used to score peptides for binding to HLA alleles or peptide- HLA immunogenicity.
- experimental observations of the display of peptides by specific HLA alleles in tumor cells can be used to score peptides for peptide-HLA binding or peptide-HLA immunogenicity.
- experimental observations of the display of peptides tumor cells by a specific HLA allele can be used to score peptides for peptide-HLA binding or peptide-HLA immunogenicity for that HLA allele.
- experimental observations of the display of peptides tumor cells can be used to score peptides for peptide-HLA binding or peptide-HLA immunogenicity, with the HLA allele(s) for a specific observed peptide selected from the HLA alleles present in the tumor that meet a predicted peptide-HLA binding or immunogenicity threshold.
- mass spectrometry is used to experimentally determine the display of peptides by tumor cells as described by Bear et al. (2021) or Wang et al. (2019) and these data are used to score for peptide-HLA binding or peptide-HLA immunogenicity.
- mass spectrometry is used to experimentally determine the display of peptides by tumor cells, and these experimental data are used to qualify the inclusion of base set (seed set) peptides for one or more HLA alleles for a vaccine.
- mass spectrometry is used to experimentally determine the display of a peptide by tumor cells, and these experimental data are used to exclude peptide- HLA binding scores or peptide-HLA immunogenicity scores for the peptide when the peptide is not observed to be displayed by an HLA allele by mass spectrometry.
- mass spectrometry is used to experimentally determine the display of peptides by tumor cells in an individual, and these experimental data are used to qualify the inclusion of base set (seed set) peptides for that individual for one or more HLA alleles.
- mass spectrometry is used to experimentally determine the display of a peptide by tumor cells in an individual, and these experimental data are used to exclude peptide-HLA binding scores or peptide-HLA immunogenicity scores for the peptide when the peptide is not observed to be displayed by an HLA allele by mass spectrometry.
- computational predictions of the immunogenicity of a peptide in the context of display by HLA alleles can used for scoring such as the methods of Ogishi et al. (2019) or Bulik-Sullivan et al. (2019).
- a peptide-HLA score or a peptide-HLA immunogenicity score for a first peptide in the base set (seed set) for a given HLA allele is eliminated and not considered during vaccine design if the wild-type peptide corresponding to the first peptide (e.g., - 83 - ActiveUS 205953775 Attorney Docket No.
- the unmutated naturally occurring form for the peptide or a peptide in the respective species within a defined sequence edit distance has a peptide-HLA score or a peptide-HLA immunogenicity score for the same HLA allele within a defined threshold.
- the threshold can be based upon the difference of the scores of the first peptide and the wild-type peptide, the ratio of the scores of the first peptide and the wild-type peptide, the score of the wild-type peptide, or other metrics.
- the defined threshold can be either greater than or less than a specified value. In some embodiments, the threshold is defined so that the wild-type peptide is not predicted to be presented.
- the method further includes running the OptiVax-Robust algorithm as described in Liu et al. (2020a) using the HLA haplotype frequencies of a population on the scored candidate set to construct a base set (also referred to as seed set herein) of target peptides (FIG.2).
- HLA diplotype frequencies can be provided to OptiVax.
- OptiVax-Robust includes algorithms to eliminate peptide redundancy that arises from the sliding window approach with varying window sizes, but other redundancy elimination measures can be used to enforce minimum edit distance constraints between target peptides in the candidate set.
- the size of the seed set is determined by a point of diminishing returns of population coverage as a function of the number of target peptides in the seed set. Other criteria can also be used, including a minimum number of vaccine target peptides, maximum number of vaccine target peptides, and desired predicted population coverage.
- a predetermined population coverage is less than about 0.4, between about 0.4 and 0.5, between about 0.5 and 0.6, between about 0.6 and 0.7, between about 0.7 and 0.8, between about 0.8 and 0.9, or greater than about 0.9.
- Another possible criterion is a minimum number of expected peptide-HLA binding hits in each individual.
- the method further includes running the OptiVax-Unlinked algorithm as described in Liu et al. (2020a) instead of OptiVax-Robust. [0515] The OptiVax-Robust method uses binary predictions of peptide-HLA immunogenicity, and these binary predictions can be generated as described in Liu et al. (2020b).
- OptiVax-Unlinked method uses the probability of target peptide binding to HLA - 84 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 alleles and can be generated as described in Liu et al. (2020a).
- OptiVax- Unlinked and EvalVax-Unlinked are used with the probabilities of peptide-HLA immunogenicity. Either method can be used for the purposes described herein, and thus the term “OptiVax” refers to either the Robust or Unlinked method.
- the observed probability of peptide-HLA immunogenicity in experimental assays can be used as the probability of peptide-HLA binding in EvalVax-Unlinked and OptiVax-Unlinked.
- the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design describe the world’s population.
- the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design are specific to a geographic region.
- the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design are specific to an ancestry.
- the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design are specific to a race.
- the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design are specific to individuals with risk factors such as genetic indicators of risk, age, exposure to chemicals, alcohol use, chronic inflammation, diet, hormones, immunosuppression, infectious agents, obesity, radiation, sunlight, or tobacco use.
- the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design are specific to individuals that carry certain HLA alleles.
- the HLA diplotypes provided to OptiVax for vaccine design describe a single individual, and are used to design an individualized vaccine.
- the base (or seed) set of target peptides e.g., first peptide set
- a base peptide is a target peptide that is included in the base or seed peptide set (e.g., first peptide set).
- the seed set (e.g., first peptide set) is based upon filtering candidate peptide scores by predicted or observed affinity or immunogenicity with respect to HLA molecules (Seed Set in FIG.1).
- some embodiments include modifications of the seed (or base) set.
- experimental assays can be used to ensure that a modified seed (or base) peptide activates T cells that also recognize the base/seed peptide. - 85 - ActiveUS 205953775 Attorney Docket No.
- the optimal anchor residue selection may depend upon the HLA allele that is binding to and displaying the target peptide and the class of the HLA allele (MHC class I or class II).
- a seed peptide set e.g., first peptide set
- a seed peptide set can become an expanded set by including anchor residue modified peptides of either MHC class I or II peptides (FIGs.1-2).
- one aspect of vaccine design is considering how to select a limited set of heteroclitic peptides that derive from the same target peptide for vaccine inclusion given that different heteroclitic peptides will have different and potentially overlapping population coverages.
- all possible anchor modifications for each base set of target peptide are considered. There are typically two anchor residues in peptides bound by MHC class I molecules, typically at positions 2 and 9 for 9-mer peptides. In some embodiments, anchors for 8-mers, 10-mers, and 11-mers are found at positions 2 and n, where n is the last position (8, 10, and 11, respectively). For MHC class I molecules, the last position n is called the “C” position herein for carboxyl terminus. In some embodiments, at each anchor position, 20 possible amino acids are attempted in order to select the best heteroclitic peptides.
- the anchor positions are determined by the HLA allele that presents a peptide, and thus the set of heteroclitic peptides includes for each set of HLA specific anchor positions, all possible anchor modifications.
- new peptide sequences with all possible anchor residue modifications are created resulting in a new heteroclitic base set (Expanded set in FIGs.1-2) that includes all of the modifications.
- anchor residue modifications of a peptide are not included in the heteroclitic base set if one or more of the peptide’s anchor residue positions - 86 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 contains a substitution mutation that distinguishes the peptide from a self-peptide.
- anchor residue modifications of a base/seed peptide are only included in the heteroclitic base set for peptide positions that do not contain a substitution mutation that distinguishes the base/seed peptide from a self-peptide. In some embodiments, anchor residue modifications of a peptide are not included in the heteroclitic base set when one or more of the peptide’s mutations does not occur between a pair of its adjacent anchor residues.
- new peptide sequences with anchor residue modifications are created resulting in a new heteroclitic base set (Expanded set in FIGs.1-2) that includes the selected modifications.
- the anchor residue positions used for modifying peptides are selected from anchor residue positions determined by the HLA alleles considered during vaccine evaluation.
- the heteroclitic base set (Expanded set in FIGs.1-2) also includes the original seed (or base) set (Seed Peptide Set in FIGs.1-2).
- the heteroclitic base set includes amino acid substitutions at non-anchor residues.
- modifications of base peptide residues is accomplished to alter binding to T cell receptors to improve therapeutic efficacy (Candia, et al.2016).
- the heteroclitic base set includes amino acid substitutions of non-natural amino acid analogs.
- the heteroclitic base set is scored for HLA affinity, peptide-HLA immunogenicity, or other metrics as described herein (another round of Peptide Scoring and Score Filtering as shown in FIGs.1- 2).
- the scoring predictions may be further updated for pairs of heteroclitic peptide and HLA allele, eliminating pairs where a heteroclitic peptide has a seed (or base) peptide from which it was derived that is not predicted to be displayed by the HLA allele at a specified threshold of peptide-HLA binding score or a specified peptide-HLA immunogenicity metric.
- a peptide-HLA score is not used for a heteroclitic peptide for a given HLA for vaccine design when the product (or other function) of the heteroclitic peptide’s peptide-HLA immunogenicity or binding probability score and the peptide-HLA immunogenicity or binding probability score for its unmodified counterpart peptide do not meet a specified threshold (e.g., 0.5, 0.6, 0.7, 0.8, or 0.9).
- a specified threshold e.g., 0.5, 0.6, 0.7, 0.8, or 0.9.
- the peptide-HLA scores may also be filtered to ensure that predicted binding cores of the heteroclitic peptide displayed by a particular HLA allele align exactly in position with the binding cores of the respective seed (or base) set target peptide for that HLA allele.
- the - 87 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 scoring predictions are filtered for an HLA allele to ensure that the heteroclitic peptides considered for that HLA allele are only modified at anchor positions determined by that HLA allele.
- Scoring produces a metric of peptide-HLA immunogenicity for peptides and HLA alleles that can be either binary, a probability of immunogenicity, or other metric of immunogenicity such as peptide-HLA affinity or percent rank, and can be based on computational predictions, experimental observations, or a combination of both computational predictions and experimental observations.
- probabilities of peptide-HLA immunogenicity are utilized by OptiVax-Unlinked.
- heteroclitic peptides are included in experimental assays such as MIRA (Klinger et al., 2015) or ELISPOT to determine their peptide-HLA immunogenicity metric with respect to specific HLA alleles.
- the methods of Liu et al. can be used to incorporate MIRA data for heteroclitic peptides into a model of peptide-HLA immunogenicity.
- peptide-HLA immunogenicity metrics of heteroclitic peptides are experimentally determined and their ability to activate T cells that also recognize the corresponding seed (or base) peptide of the heteroclitic peptide is performed as is known in the art to qualify the heteroclitic peptide for vaccine inclusion (e.g., Houghton et al., 2007).
- these assays of the immunogenicity and cross-reactivity of heteroclitic peptides are performed when the heteroclitic peptides are displayed by specific HLA alleles.
- experimental observations of the display of heteroclitic peptides by specific HLA alleles in cells can be used to score peptides for peptide-HLA binding or peptide-HLA immunogenicity.
- mass spectrometry is used to experimentally determine the display of heteroclitic peptides by cells as described by Bear et al. (2021) or Wang et al. (2019) and these data are used to score for peptide-HLA binding or peptide-HLA immunogenicity.
- mass spectrometry is used to experimentally determine the display of heteroclitic peptides by cells, and these experimental data are used to qualify the inclusion of heteroclitic peptides for inclusion in a vaccine.
- mass spectrometry is used to experimentally determine the display of a peptide by tumor cells, and these experimental data are used to exclude peptide-HLA binding scores or peptide-HLA immunogenicity scores for the peptide when the peptide is not observed to be displayed by an HLA allele by mass spectrometry.
- mass spectrometry is used to experimentally determine the display of a heteroclitic peptide by cells with an HLA - 88 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 allele found in an individual, and these experimental data are used to qualify the inclusion of the heteroclitic peptide for inclusion in a vaccine for the individual.
- mass spectrometry is used to experimentally determine the display of a peptide by tumor cells in an individual, and these experimental data are used to exclude peptide-HLA binding scores or peptide-HLA immunogenicity scores for the peptide when the peptide is not observed to be displayed by an HLA allele by mass spectrometry.
- computational predictions of the immunogenicity of a heteroclitic peptide in the context of display by HLA alleles can used for scoring such as the methods of Ogishi et al. (2019) or Bulik-Sullivan et al. (2019).
- a peptide in the heteroclitic base set is removed if (1) one of its anchor positions for an HLA allele corresponds to the location of a mutation in the base/seed peptide from which it was derived that distinguishes the base/seed peptide from a self-peptide, and (2) if the peptide-HLA binding or peptide-HLA immunogenicity of the self-peptide is stronger than a specified threshold for self-peptide binding or immunogenicity. This eliminates peptides in the heteroclitic base set that may cross-react with self-peptides as a result of sharing TCR facing residues with self-peptides.
- the threshold for self-peptide binding is between approximately 500 nM to 1000 nM.
- redundant peptides in the heteroclitic base set are removed.
- a redundant peptide is a first heteroclitic peptide that has peptide-HLA immunogenicity scores or peptide-HLA binding scores that are less immunogenic for all scored HLAs than a second heteroclitic peptide in the heteroclitic base set, where both the first and second heteroclitic peptides are derived from the same base (or seed) peptide.
- peptide redundancy is determined by only comparing peptide-HLA immunogenicity scores or peptide-HLA binding scores for HLA alleles where the peptide-HLA immunogenicity scores or peptide-HLA binding scores for both peptides for an HLA allele are more immunogenic than a given threshold (e.g., 50 nM for binding).
- a given threshold e.g. 50 nM for binding
- a redundant peptide is a first heteroclitic peptide that has an average peptide-HLA immunogenicity score or peptide-HLA binding score that is less immunogenic than the average peptide-HLA immunogenicity score or peptide-HLA binding score of a second heteroclitic peptide in the heteroclitic base set, where both the first and second heteroclitic peptides are derived from the same base (or seed) peptide, and the average scores are computed for HLA alleles where the peptide-HLA immunogenicity scores or peptide-HLA binding scores for both - 89 - ActiveUS 205953775 Attorney Docket No.
- a redundant peptide is a first heteroclitic peptide that has a weighted peptide-HLA immunogenicity score or peptide-HLA binding score that is less immunogenic than the weighted peptide-HLA immunogenicity score or peptide-HLA binding score of a second heteroclitic peptide in the heteroclitic base set, where both the first and second heteroclitic peptides are derived from the same base (or seed) peptide, and where the weighting is determined by the frequency of the HLA allele in a human population, and the weighted scores are computed for HLA alleles where the peptide-HLA immunogenicity scores or peptide- HLA binding scores for both peptides for an HLA allele are more immunogenic that a given threshold (e.g.,
- the next step involves scoring the heteroclitic base set (the second peptide set) and filtering the resulting scores to create a second peptide set by comparing the peptide-HLA immunogenicity scores or peptide-HLA binding scores of the peptides for one or more HLA alleles to a threshold.
- an affinity criterion of about 50 nM is used to increase the probability that a vaccine peptide will be found and displayed by HLA molecules.
- the affinity criteria is more constrained than 50 nM (i.e., ⁇ 50 nM).
- the affinity criteria is more constrained than about 500 nM (i.e., ⁇ 500 nM).
- individual peptide-HLA binding scores or immunogenicity metrics are determined and thus a peptide may be retained as long as it meets the criteria for at least one HLA allele, and only peptide-HLA scores that meet the criteria are considered for vaccine design.
- probabilistic thresholds are used in the peptide scoring and score filtering steps (FIGs.1-2) to filter peptide-HLA combinations for vaccine design.
- a credence function is used to predict the probability of peptide-HLA display or peptide-HLA immunogenicity for each peptide for a desired set of HLA alleles.
- a credence function implementation fits the output of a binding prediction algorithm (such the EL or BA output of NetMHCpan4.1 or NetMHCIIpan4.0) to observed held- out binding or immunogenicity data.
- a binding prediction algorithm such as the EL or BA output of NetMHCpan4.1 or NetMHCIIpan4.0
- One implementation of credence functions is described in Dai, Z., & Gifford, D. “Constrained Submodular Optimization for Vaccine Design”.
- arXiv preprint arXiv:2206.08336. https://arxiv.org/abs/2206.08336, Version 2, 27 January 2023.
- Held-out data is experimental data that is not used to train the binding prediction algorithm.
- held-out data contains examples of experimentally verified peptide-HLA - 90 - ActiveUS 205953775 Attorney Docket No.
- held-out data describes known peptide-HLA binding pairs, and peptides surrounding known binders in these held-out data are used to generate negative examples of binding which is added to the held-out data.
- the credence function that maps the output of a prediction algorithm to a probability of binding (or immunogenicity) is selected to minimize the difference between the output of the prediction algorithm on peptides examples in the held-out data and the experimentally observed binding (or immunogenicity) in the held-out data. For example, when the held-out data contains an experimentally verified peptide-HLA binding pair, the output of the credence function should assign this peptide-HLA pair a high probability of binding.
- this is accomplished by dividing the output of the prediction algorithm into discrete intervals (“bins”) and for each bin choosing a function that maps the output of the prediction algorithm that are contained in that bin into the observed fraction of binding (or immunogenicity) in the held-out experimental data.
- the functions for each interval are chosen so that increasing intervals have increasing probabilities of binding (or immunogenicity).
- the process of fitting a credence function is repeated on different sets of held-out data, and the difference between the credence functions on each set of held-out data is used to validate the accuracy of the credence function.
- the first peptide scoring and filtering step uses a credence function to predict the probability of binding (or immunogenicity) for all combinations of candidate peptides and HLA alleles. In some embodiments, the first peptide scoring and filtering step eliminates peptide-HLA combinations that do not bind (or are not immunogenic) stronger than a probability threshold for the respective HLA allele. In some embodiments, the second peptide scoring and filtering step eliminates peptide-HLA combinations where (1) the peptide’s corresponding base peptide-HLA combination was eliminated in the first peptide scoring and filtering step, or (2) the peptide-HLA combination does not have a probability greater than a second more stringent probability threshold.
- the second peptide scoring and filtering step uses a function to combine the peptide-HLA display (or immunogenicity) probability of a base peptide with the peptide-HLA display (or immunogenicity) probability of its heteroclitic derivative, and the result of the function must be greater than a threshold to keep the peptide-HLA combination for the heteroclitic derivative.
- the combination function is multiplication.
- the result of the combination function is used as the peptide-HLA metric for that peptide for vaccine design. - 91 - ActiveUS 205953775 Attorney Docket No.
- the next step involves inputting the second peptide set to OptiVax to select a compact set of vaccine peptides that maximizes predicted vaccine performance (Vaccine Performance Optimization; FIGs.1-2).
- predicted vaccine performance is a function of expected peptide-HLA binding affinity (e.g., a function of the distribution of peptide-HLA binding affinities across all peptide-HLA combinations for a given peptide set, or weighted by the occurrence of the HLA alleles in a population or individual).
- predicted vaccine performance is the expected population coverage of a vaccine.
- predicted vaccine performance is the expected number peptide-HLA hits produced by a vaccine in a population or individual. In some embodiments, predicted vaccine performance requires a minimum expected number of peptide- HLA hits (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more) produced by a vaccine. In some embodiments, predicted vaccine performance is a function of population coverage and expected number of peptide-HLA hits desired produced by a vaccine. In some embodiments, predicted vaccine performance is a metric that describes the overall immunogenic properties of a vaccine where all of the peptides in the vaccine are scored for peptide-HLA immunogenicity for two or more HLA alleles (e.g., three or more HLA alleles).
- predicted vaccine performance is the expected fraction of HLA alleles in a single individual that have a minimum number of peptides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more) with predicted peptide-HLA immunogenicity produced by a vaccine.
- a vaccine is designed by the iterative selection of peptides from the heteroclitic base set (also referred to as Expanded set as shown in FIGs.1-2) at progressively less stringent criteria for predicted peptide immunogenicity or display.
- a peptide is retained if at least one of its peptide-HLA scores is not eliminated by the thresholds employed.
- OptiVax is first used to design a vaccine with a desired vaccine performance with specific peptide qualification criteria (e.g., seed HLA-peptide scores from the candidate set must bind to at least one MHC molecule at 500 nM or stronger, - 92 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 and peptide-HLA scores from the expanded set must bind to at least one MHC molecule at 50 nM or stronger).
- specific peptide qualification criteria e.g., seed HLA-peptide scores from the candidate set must bind to at least one MHC molecule at 500 nM or stronger, - 92 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 and peptide-HLA scores from the expanded set must bind to at least one MHC molecule at 50 nM or stronger.
- the vaccine that results from this application of OptiVax is then used as the foundation for vaccine augmentation with less stringent criteria (e.g., seed peptide-HLA scores from the candidate set must bind to at least one MHC molecule at 1000 nM or stronger, and peptide HLA-scores from the expanded set must bind to at least one MHC molecule at 100 nM or stronger) to further improve the desired vaccine performance.
- stringent criteria e.g., seed peptide-HLA scores from the candidate set must bind to at least one MHC molecule at 1000 nM or stronger, and peptide HLA-scores from the expanded set must bind to at least one MHC molecule at 100 nM or stronger
- Methods for vaccine augmentation are described in Liu et al. (2020b), incorporated by reference in its entirety herein.
- multiple rounds of vaccine augmentation may be utilized.
- the final augmented vaccine is the one selected.
- selection of peptide sets to meet a desired predicted vaccine performance can be accomplished by computational algorithms other than OptiVax.
- integer linear programming or mixed-integer linear programming is employed for selecting peptide sets instead of OptiVax.
- One example of an integer programming method for peptide set selection is described by Toussaint et al., 2008, incorporated by reference in its entirety herein.
- An example solver for mixed-integer linear programming is Python-MIP that can be used in conjunction with Toussaint et al., 2008.
- a second example of methods for vaccine peptide selection is described in “Maximum n-times Coverage for Vaccine Design” by Liu et al.
- Predicted vaccine performance refers to a metric. Predicted vaccine performance can be expressed as a single numerical value, a plurality of numerical values, any number of non- numerical values, and a combination thereof. The value or values can be expressed in any mathematical or symbolic term and on any scale (e.g., nominal scale, ordinal scale, interval scale, or ratio scale).
- a seed (or base) peptide and all of the modified peptides that are derived from that seed (or base) peptide comprise a single peptide family.
- a maximum number of peptides e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more
- This limit on peptide family immunogenicity limits the credit caused by many modified versions of the same base peptide.
- the methods described herein are included for running OptiVax with an EvalVax objective function that corresponds to a desired metric of predicted vaccine performance.
- population coverage means the - 93 - ActiveUS 205953775 Attorney Docket No.
- the metric of population coverage is computed using the HLA haplotype frequency in a given population such as a representative human population. In some embodiments, the metric of population coverage is computed using marginal HLA frequencies in a population.
- Maximizing population coverage means selecting a peptide set (either a base peptide set, a modified peptide set, or a combination of base and modified peptides; e.g., a first peptide set, second peptide set, or third peptide set) that collectively results in the greatest fraction of the population that has at least a minimum number (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more) of immunogenic peptide-HLA bindings based on proportions of HLA haplotypes in a given population (e.g., representative human population).
- a minimum number e.g. 1, 2, 3, 4, 5, 6, 7, 8, or more
- this process includes the OptiVax selection of heteroclitic peptides (as described in this disclosure) that activate T cells that respond to their corresponding seed (or base) peptide and the heteroclitic base peptides to improve population coverage.
- the seed (or base) target peptides are always included in the final vaccine design.
- peptides are only considered as candidates for a vaccine design (e.g., included in a first, second, and/or third peptide set) if they have been observed to be immunogenic in clinical data, animal models, or tissue culture models.
- vaccine peptides are selected to be displayed by a peptide specific set of HLA class I or class II alleles, wherein for at least two peptides in a vaccine all of the peptide specific sets of HLA class I or class II alleles are not identical.
- heteroclitic peptides are used as exemplary embodiments in this disclosure, any modified peptide could be used in place of a heteroclitic peptide.
- a modified peptide is a peptide that has one or more amino acid substitutions of a target base/seed peptide. The amino acid substitution could be located at an anchor position or any other non-anchor position.
- a candidate vaccine peptide e.g., a base peptide or a modified peptide
- a candidate vaccine peptide is eliminated from vaccine inclusion if it activates T cells that recognize self-peptides (e.g., this can be achieved at the first and/or second round of Peptide Filtering and Sorting as shown in FIGs.1-2).
- a candidate vaccine peptide e.g., a base peptide or a modified peptide
- a candidate vaccine peptide is computationally eliminated from vaccine inclusion if its outward facing amino acids, when bound by an HLA allele, are similar to outward facing self-peptide residues that are presented by the same HLA allele, where similarity can be defined by identity or similarity metrics such as BLOSUM matrices (BLOSUM matrices are known in the art).
- BLOSUM matrices BLOSUM matrices are known in the art.
- calculation of the percent identity of two nucleic acid or polypeptide sequences can be performed by aligning the two sequences for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second sequences for optimal alignment and non-identical sequences can be disregarded for comparison purposes).
- the comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm.
- the percent identity between two protein sequences can be determined by aligning the proteins and then computing the percentage of residues that are identical as described in Wang et al. (BMC Bioinformatics 19, 529 (2016).
- testing a vaccine peptide for its ability to activate T cells that recognize self-peptides can be experimentally accomplished by the vaccination of animal models followed by ELISPOT or other immunogenicity assay or with human tissue protocols. In both cases, models with HLA alleles that present the vaccine peptide are used.
- human primary blood mononuclear cells (PBMCs) are stimulated with a vaccine peptide, the T cells are allowed to grow, and then T cell activation with a self-peptide is assayed as described in Tapia-Calle et al. (2019) or other methods as known in the art.
- the vaccine peptide is excluded from vaccine inclusion if the T cells are activated by the self-peptide.
- computational predictions of the ability of a peptide to activate T cells that also recognize self-peptides can be utilized. These predictions can be based upon the modeling of the outward facing residues from the peptide-HLA complex and their interactions with other peptide residues.
- a candidate vaccine peptide e.g., a base peptide or a modified peptide
- a candidate vaccine peptide is eliminated from vaccine inclusion or experimentally tested for cross-reactivity if it is predicted to activate T cells that also recognize self-peptides based upon the structural similarity of the peptide-MHC complex of the candidate peptide (e.g., a base peptide or a modified peptide) and the peptide-MHC complex of a self-peptide.
- the peptide-HLA binding score or peptide-HLA immunogenicity metric for a candidate heteroclitic vaccine peptide (e.g., a modified peptide) and HLA allele is eliminated from consideration during vaccine design if the candidate heteroclitic vaccine peptide does not activate T cells that recognize its corresponding base/seed target peptide (second round of Peptide Scoring and Score Filtering, FIGs.1-2) for the given HLA allele.
- a heteroclitic vaccine peptide (e.g., a modified peptide) is - 95 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 eliminated from a vaccine design if the candidate heteroclitic vaccine peptide does not activate T cells that recognize its corresponding base/seed target peptide (second round of Peptide Scoring and Score Filtering, FIGs.1-2) for a given HLA allele.
- a candidate heteroclitic peptide e.g., a modified peptide
- testing a candidate heteroclitic peptide for its ability to activate T cells that recognize its corresponding seed (or base) target peptide with respect to the same HLA allele can be experimentally accomplished by the vaccination of animal models followed by ELISPOT or other immunogenicity assay or with human tissue protocols. In both cases, models with HLA alleles that present the heteroclitic peptide are used.
- human PBMCs are stimulated with the heteroclitic peptide, the T cells are allowed to grow, and then T cell activation with the seed (or base) target peptide is assayed as described in Tapia-Calle et al. (2019) or using other methods known in the art.
- computational predictions of the ability of a heteroclitic peptide to activate T cells that also recognize the corresponding seed (or base) target peptide can be utilized. These predictions can be based upon the modeling of the outward facing residues from the peptide-HLA complex and their interactions with other peptide residues.
- the structural similarity of the peptide-HLA complex of a heteroclitic peptide and the peptide-HLA complex of the corresponding seed (or base) target is used to qualify heteroclitic peptides for vaccine inclusion or to require experimental immunogenicity testing before vaccine inclusion.
- TCR Interface Divergence is the Least Root Mean Square Deviation of the difference between a first peptide’s TCR facing residues’ 3D positions and the corresponding residue positions of a second peptide with respect to a specific HLA allele.
- other metrics are used for the TCRID instead of Least Root Mean Square Deviation.
- other metrics are used for the TCRID that include position deviations in non-TCR facing residues and MHC residues from the specific HLA allele.
- TCRID is used to predict if two peptides when displayed by a given HLA allele will activate the same T cell clonotypes.
- FlexPepDock (London et al., 2011, incorporated by reference in its entirety herein) or DINC (Antunes et al., 2018, incorporated by reference in its entirety herein) in conjunction with the crystal structures of HLA molecules can be used to compute TCRID metrics for pairs of peptides given an HLA molecule.
- TCRID is computed by (1) determining the 3D peptide-HLA structures for two different peptides bound by a specific HLA allele, (2) aligning the HLA alpha helices of the peptide-HLA structures, and (3) computing the Least Root Mean Square Deviation of the - 96 - ActiveUS 205953775 Attorney Docket No.
- the second Peptide Scoring and Score Filtering step in FIGs.1 and 2 will eliminate the peptide-HLA binding or immunogenicity score for a heteroclitic peptide for a specific HLA allele when the HLA specific TCRID between the heteroclitic peptide and its corresponding base (or seed) peptide from which it was derived is over a first TCRID threshold.
- the second Peptide Scoring and Score Filtering step in FIGs.1 and 2 will eliminate all peptide-HLA binding or immunogenicity scores for a heteroclitic peptide when the HLA specific TCRID between the heteroclitic peptide and its corresponding unmutated self- peptide from which it was derived is under a second TCRID threshold.
- the first Peptide Scoring and Score Filtering step in FIGs.1 and 2 will eliminate all peptide-HLA binding or immunogenicity scores for a candidate peptide when the HLA specific TCRID between the peptide and its corresponding unmutated self-peptide is under a third TCRID threshold.
- any of the TCRID thresholds are determined by experimentally observing or computationally predicting the cross-reactivity of TCR molecules to peptide-HLA complexes.
- FIG.3 (MHC class I) and FIG.4 (MHC class II) show the predicted population coverage of OptiVax-Robust selected single target-specific vaccines with differing number of peptides designed for selected mutations in the BRAF, CTNNB1, KRAS, PIK3CA, and TP53 genes.
- FIGs.3-4 show that as the number of peptides increases for a vaccine, its predicted population coverage increases. The population coverage shown in FIGs.3-4 are of those individuals that have the specific mutation that the vaccine is designed to cover.
- OptiVax can be used to design a vaccine to maximize the fraction/proportion of the population whose HLA molecules are predicted to bind to and display at least p peptides from the vaccine.
- this prediction e.g., scoring
- the number p is input to OptiVax, and OptiVax can be run multiple times with varying values for p to obtain a predicted optimal target peptide set for different peptide counts p.
- p Larger values of p will increase the redundancy of a vaccine at the cost of more peptides to achieve a desired population coverage. In some embodiments, it may not be possible to achieve a given population coverage - 97 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 given a specific heteroclitic base set. In some embodiments, the number p is a function of the desired size of a vaccine. [0541] The methods described herein can be used to design separate vaccine formulations for MHC class I and class II-based immunity. [0542] In some embodiments, this procedure is used to create a vaccine for an individual.
- the target peptides present in the individual are determined by sequencing the individual’s tumor RNA or DNA, and identifying mutations that produce foreign peptides.
- sequencing the individual is described in U.S. Patent No.10,738,355, incorporated by reference in its entirety herein.
- peptide sequencing methods are used to identify target peptides in the individual. One embodiment of this is described in U.S. Patent Publication No.2011/0257890.
- the target peptides used for the individual’s vaccine are selected when a self-peptide, foreign peptide, pathogen peptide or RNA encoding a self-peptide, foreign peptide, or pathogen peptide observed in a specimen from the individual is present at a predetermined level.
- the target peptides in the individual are used to construct a vaccine as disclosed herein.
- OptiVax is provided a diplotype comprising the HLA type of the individual.
- the HLA type of an individual is separated into multiple diplotypes with frequencies that sum to one, where each diplotype comprises one or more HLA alleles from the individual and a notation that the other allele positions should not be evaluated.
- FIG.5 shows the predicted vaccine performance (predicted number of peptide-HLA hits) of ten example G12V MHC class I vaccines for a single individual with the MHC class I HLA diplotype HLA-A02:03, HLA-A11:01, HLA-B55:02, HLA-B58:01, HLA-C03:02, HLA- C03:03.
- OptiVax was used to design ten G12V MHC class I vaccines for this HLA diplotype with peptide counts ranging from 1 to 10. For the results in FIG.5, OptiVax was run with six synthetic diplotypes, each equally weighted, each with one HLA allele from the individual’s HLA diplotype, and the other allele positions marked to not be evaluated. - 98 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 MHC Class I Vaccine Design Procedure [0544] In some embodiments, MHC class I vaccine design procedures consist of the following computational steps.
- the inputs for the computation are: sequence (length n) containing the neoantigen(s) or pathogenic target(s) of interest (e.g., KRAS G12D, KRAS G12V, KRAS G12R, KRAS G12C, KRAS G13D).
- Substitution mutation ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ , ⁇ ⁇ ⁇ ⁇ ⁇ is true if the mutation is a substitution, and false if the mutation is a deletion or insertion or the peptide does not contain a mutation (such as in pathogen targets). When the mutation is a deletion or insertion then t indicates the position immediately before the deletion or insertion.
- ⁇ ⁇ Threshold for potential presentation of peptides by MHC for peptide-MHC scoring (e.g., 500 nM binding affinity)
- ⁇ ⁇ Threshold for predicted display of peptides by MHC for peptide-MHC scoring (e.g., 50 nM binding affinity)
- H Set of HLA alleles (for HLA-A, HLA-B, HLA-C loci)
- F R: Population haplotype frequencies (for OptiVax optimization and coverage evaluation).
- Peptide-HLA Scoring Functions used are: ScorePotential : ⁇ ⁇ R: Scoring function mapping a (peptide, HLA allele) pair to a prediction of peptide-HLA display. If predicted affinity ⁇ ⁇ 1 , then returns 1, else returns 0. Options include MHCflurry, NetMHCpan, PUFFIN, ensembles, or alternative metrics or software may be used, including models calibrated against immunogenicity data. SCOREDISPLAY : ⁇ ⁇ H ⁇ R: Scoring function mapping a (peptide, HLA allele) pair to a prediction of peptide-HLA display. If predicted affinity ⁇ ⁇ 2, then returns 1, else returns 0.
- ⁇ ⁇ ⁇ ⁇ ⁇ ,..., ⁇ ⁇ ⁇ ⁇ 1 ⁇ [0548]
- the second condition j ⁇ ⁇ t – (k-1), t – 1 ⁇ excludes peptides where the mutation at t is in positions P2 or Pk of the windowed k-mer peptide (i.e., the anchor positions) and the mutation is a substitution.
- B contains the native peptides that are predicted to be potentially presented by at least 1 HLA.
- ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 Create a set of all heteroclitic peptides B' stemming from peptides in B: where ANCHOR-MODIFIED(b) returns a set of all 399 anchor-modified peptides stemming from b (with all possible modifications to the amino acids at P2 and P9).
- OptiVax-Robust is used to design a final peptide set (e.g., third peptide set) from the union of base peptides and heteroclitic peptides B ⁇ B' (with corresponding scoring matrices S and ⁇ ⁇ ⁇ for B and B', respectively).
- OptiVax will output m sets ⁇ ⁇ for s ⁇ [1, ..., m] where m is the largest vaccine size requested from OptiVax.
- ⁇ ⁇ denote the compact set of vaccine peptides output by OptiVax containing k peptides. Note that ⁇ ⁇ is not necessarily a superset of ⁇ ⁇ .
- OptiVax can be used to augment the base set B with peptides from B' using scoring matrix ⁇ ⁇ ⁇ to have OptiVax return set ⁇ ⁇ , and the final vaccine set of peptides ⁇ ⁇ ⁇ ⁇ . [0553] In some embodiments, this procedure is repeated independently for each target of interest, and the resulting independent vaccine sets can be merged into a combined vaccine as described below. - 101 - ActiveUS 205953775 Attorney Docket No.
- MHC class II vaccine design procedures consist of the following computational steps.
- the inputs for the computation are: sequence(s) (length n) containing the neoantigen(s) or pathogenic target(s) of interest (e.g., KRAS G12D, KRAS G12V, KRAS G12R, KRAS G12C, KRAS G13D).
- Substitution mutation ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ , ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ is true if the mutation is a substitution, and false if the mutation is a deletion or insertion or the peptide does not contain a mutation (such as for pathogen targets). When the mutation is a deletion or insertion then t indicates the position immediately before the deletion or insertion.
- ⁇ ⁇ Threshold for potential presentation of peptides by MHC for peptide-MHC scoring (e.g., 500 nM binding affinity)
- ⁇ ⁇ Threshold for predicted display of peptides by MHC for peptide-MHC scoring (e.g., 50 nM binding affinity)
- H Set of HLA alleles (for HLA-DR, HLA-DQ, HLA-DP loci)
- F H ⁇ ⁇
- R Population haplotype frequencies (for OptiVax optimization and coverage evaluation).
- N Parameter for EvalVax and OptiVax objective function. Specifies minimum number of predicted per-individual hits for population coverage objective to consider the individual covered.
- Peptide-HLA Scoring Functions used are: SCOREPOTENTIAL : ⁇ ⁇ H ⁇ R: Scoring function mapping a (peptide, HLA allele) pair to a prediction of display. If predicted affinity ⁇ ⁇ 1 , then returns 1, else returns 0. Options include NetMHCIIpan, PUFFIN, ensembles, or alternative metrics or software may be used, including models calibrated against immunogenicity data. SCOREDISPLAY : ⁇ ⁇ H ⁇ R: Scoring function mapping a (peptide, HLA allele) pair to a prediction of peptide-HLA display. If predicted affinity ⁇ ⁇ 2 , then returns 1, else returns 0.
- matrix S 1 : S 1 [p, h] SCOREPOTENTIAL(p, h) ⁇ p ⁇ ⁇ , h ⁇ H Note that S1 is a binary matrix where 1 indicates the HLA is predicted to potentially present the peptide, and 0 indicates no potential presentation. [0559] For each (peptide, HLA allele) pair (p, h), identify/predict the 9-mer binding core using FINDCORE.
- P t can be located outside of the core or inside the core in a non-anchor position.
- Pt can only be located at specific positions inside and/or outside of the core.
- the binding core predictions in C are accompanied by prediction confidences.
- OptiVax-Robust is run with peptides ⁇ and scoring matrix S2 to identify a non- redundant base set of peptides B ⁇ ⁇ .
- B can be chosen as the entire set ⁇ rather than identifying a non-redundant base set.
- B can be chosen as the entire set ⁇ rather than identifying a non-redundant base set.
- the heteroclitic set B' contains all anchor-modified peptides b' with modifications to all unique cores of b identified for any HLA alleles that potentially present b with a valid core position as indicated by scoring matrix S2.
- OptiVax-Robust is used to design a final peptide set (e.g., third peptide set) from the union of base peptides and heteroclitic peptides B ⁇ B' (with corresponding scoring matrices S2 and ⁇ ⁇ ⁇ for B and B', respectively).
- OptiVax will output m sets ⁇ ⁇ for s ⁇ [1, ..., m] where m is the largest vaccine size requested from OptiVax.
- ⁇ ⁇ denote the compact set of vaccine peptides output by OptiVax containing k peptides. Note that ⁇ ⁇ is not necessarily a superset of ⁇ ⁇ .
- OptiVax can be used to augment the base set B with peptides from B' using scoring matrix ⁇ ⁇ ⁇ to have OptiVax return set and the final vaccine set ⁇ ⁇
- this procedure is repeated independently for each single target of interest, and the resulting independent vaccine sets can be merged into a combined vaccine as described below.
- - 105 - ActiveUS 205953775 Attorney Docket No.
- peptide sequences that are more conserved across strains, species, or other protein sources of interest are prioritized for vaccine inclusion.
- a set of related protein sequences called protein variants are considered for vaccine design.
- a protein variant is one instance of a family of protein sequences, and protein variants can be sequences from various species, pathogen strains (e.g., viral strains), or other variations considered for vaccine design.
- each considered protein variant has an associated probability called a protein variant probability, where the sum of all protein variant probabilities for the supplied set of protein variants is one.
- multiple proteins of interest can be considered for the design of a single vaccine using an MHC Class I or Class II vaccine design method prioritizing peptide conservation.
- protein variants for all proteins of interest are collectively considered for generating candidate peptides.
- the protein variant probabilities across all of the considered multiple proteins sum to one.
- the methods disclosed herein can be used to design an immunogenic composition, such as a vaccine, based on any protein variant, including variants that have yet to be discovered or future emerging variants (e.g., new virus species or strains).
- a set of candidate peptides are created from each protein variant using a sliding window method that parses the protein variant into peptide sequences.
- MHC Class I 8-mers, 9-mers, 10-mers, and/or 11-mers are produced, but this process can be performed with any desired window lengths and the resulting peptide sets can be combined. In some embodiments, for MHC Class I, only 9-mers are produced. In some embodiments, for MHC Class II, all windowed peptides of length 13–25 are produced, but this process can be performed using any desired window lengths (e.g., only 15-mers). In some embodiments, peptides that are predicted to be glycosylated in a given protein variant are removed and not considered for that variant as described in Liu et al. (2020a), which is incorporated by reference herein in its entirety.
- conservation is defined as the fraction of input protein variants where the peptide sequence occurs. For example, if a given 9-mer peptide sequence occurs in the peptides generated from 90% of the protein variants provided as input, its conservation is .90. In some embodiments, conservation is defined for each generated peptide sequence (MHC Class I or Class II) as the - 106 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sum of the protein variant frequencies where the peptide sequence occurs.
- COMPUTECONSERVATION computes the sum of the frequencies of the protein variants that contain a peptide sequence.
- a method of predicting conservation can be used to implement COMPUTECONSERVATION, such as the one disclosed in Hie et al. (2021), which is incorporated by reference herein in its entirety.
- vaccine design considers conservation by prioritizing peptides for vaccine inclusion that are more conserved than others to meet a desired vaccine performance metric.
- the vaccine design method attempts to first design a vaccine with candidate peptides that all meet a first conservation threshold, and if the desired vaccine performance is not met, it iteratively adds additional peptides with less stringent conservation to attempt to meet the desired vaccine performance metric.
- vaccine design prioritizing conservation proceeds by setting a vaccine design D to be an empty set, and then performing the steps of: (1) selecting candidate peptides in which each peptide passes a conservation threshold to create a candidate peptide set and is not in D, (2) selecting vaccine designs having varying peptide numbers/combinations from this candidate set to optimize a vaccine performance metric using methods disclosed herein for MHC Class I or Class II vaccine design to augment the vaccine design contained in D (one implementation of vaccine augmentation is described in (Liu et al., 2021), incorporated by reference in its entirety herein), (3) selecting the smallest vaccine peptide set design from Step 2 that either meets the desired vaccine performance metric or where adding one more peptide to the selected set does not provide a desired minimum improvement in the vaccine performance metric, (4) if a vaccine peptide set was found in Step 3, adding the vaccine peptide set design from Step 3 to the vaccine design D, and (5) determining whether the vaccine design D meets a desired vaccine performance metric objective, and if so
- Step 5 the vaccine design D fails to meet the desired vaccine performance metric objective
- the computation continues with the following steps: (6) setting an updated conservation threshold to be lower than the current conservation threshold (less constrained) and (7) repeating the process starting from Step 1, retaining the current vaccine design D and current candidate set, until either a desired vaccine performance metric objective is reached at Step 5, or the updated conservation threshold is lower than a minimum desired conservation threshold at Step - 107 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 6. If on any iteration the updated conservation threshold is lower than a minimum desired conservation threshold, the latest version of vaccine design D will be used as the final vaccine design.
- the final vaccine design D includes all of the peptides that can be used in a vaccine.
- MHC class I or class II vaccine design procedures consist of the following computational steps.
- the inputs for the computation are: sequence of protein variant j of length nj.
- ⁇ ⁇ , ⁇ denotes the amino acid at position i of protein variant j, where ⁇ ⁇ [1, ... ⁇ ] and a is the number of protein variants ⁇ ⁇ : Protein variant probability of protein variant ⁇ ⁇ tj: Position in protein variant ⁇ ⁇ of the target mutation ⁇ ⁇ [ 1, ... ⁇ ]
- D The vaccine design, initialized to the empty set ⁇ s: Substitution mutation ⁇ ⁇ [ ⁇ ⁇ ⁇ ⁇ , ⁇ ⁇ ⁇ ⁇ ⁇ ] is true if the mutation is a substitution, and false if the mutation is a deletion or insertion or the peptide does not contain a mutation.
- t indicates the position immediately before the deletion or insertion.
- ⁇ ⁇ Initial conservation level of peptides
- ⁇ ⁇ Current conservation threshold
- ⁇ ⁇ Change in conservation level on each iteration
- ⁇ ⁇ Minimum final conservation
- v Target vaccine performance metric
- ⁇ ⁇ Minimum change in vaccine performance metric to increase vaccine size
- COMPUTECONSERVATION ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ R: In some embodiments, computes the fraction of sets X j that contain sequence S. In some embodiments, sums all the O j where sequence S appears in X j - 108 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0575]
- the protein variant sequences ⁇ ⁇ are used to produce windowed peptides that span the protein sequence(s) starting at each location m with a peptide length of k residues. The result is the set X j that contains all of the peptide sequences in protein variant P j .
- ⁇ ⁇ , ⁇ ... ⁇ ( ⁇ ) only produces a sequence when the subscripts are within the range of the defined protein Pj.
- k is chosen to produce 8-mers, 9-mers, 10-mers, and/or 11-mers, but this process can be performed with any desired window lengths and the resulting peptide sets can be combined.
- 9-mers are produced.
- all windowed peptides of length 13–25 are extracted, but this process can be performed using any desired window lengths (e.g., only 15-mers).
- the second condition m ⁇ ⁇ t – (k-1), t – 1 ⁇ excludes peptides where the mutation at t is in positions P2 or Pk of the windowed k-mer peptide (i.e., the anchor positions) and the mutation is a substitution for MHC Class I design.
- MHC Class II anchor positions are filtered in the MHC Class II design method.
- the methods disclosed herein are used to create the set of all peptides B that occur in any input protein variant.
- candidate peptides are selected where each peptide passes a conservation threshold to create a candidate peptide set and is not already in D.
- a set of peptide candidates ⁇ is defined such that each candidate peptide meets the current conservation threshold c ⁇ and the peptide candidate is not already in D.
- D is set to be empty (0 peptides) on the first iteration of the computational steps.
- vaccine designs are selected having varying peptide numbers/combinations from the candidate set to optimize a vaccine performance metric using methods disclosed herein for MHC Class I or Class II vaccine design to augment the vaccine design contained in D.
- the peptide set ⁇ is provided to “MHC Class I Vaccine Design Procedure with Defined Peptide Set ⁇ ” for MHC Class I and “MHC Class II Vaccine Design Procedure with Defined Peptide Set ⁇ ” for MHC Class II.
- the peptide set ⁇ is provided as the set of candidates to augment the set D. Both the set ⁇ and D are provided to OptiVax which uses D as the fixed starting set and augments D with peptides from the set ⁇ using vaccine augmentation as described in Liu et al., 2021, incorporated by reference in its entirety herein.
- OptiVax-Robust is used to augment the set D with peptides from ⁇ using the scoring matrices as defined in “MHC Class I Vaccine Design Procedure with Defined Peptide Set ⁇ ” for MHC Class I and “MHC Class II Vaccine Design Procedure with Defined Peptide Set ⁇ ” for MHC Class II, and returns sets ⁇ ⁇ where each set ⁇ ⁇ is a compact set of vaccine peptides output by OptiVax containing s peptides.
- the steps to modify anchor positions are not utilized in the MHC Class I or MHC Class II vaccine design methods and only the base peptides B are utilized for vaccine design.
- positions in addition to anchor positions are modified in the MHC Class I or MHC Class II vaccine design methods utilized to create B’.
- the smallest vaccine peptide set design is selected from Step 2 that either meets the desired vaccine performance metric or where adding one more peptide to the selected set does not provide a desired minimum improvement in the vaccine performance metric.
- a vaccine design ⁇ ⁇ is chosen that meets minimum requirements.
- the vaccine design ⁇ ⁇ is chosen with the value s chosen to be the minimum value of s such that the difference in vaccine performance between D ⁇ ⁇ ⁇ and D ⁇ ⁇ ⁇ is less than v ⁇ .
- the value s is chosen to be the minimum value such that the - 110 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 vaccine performance metric of D ⁇ meets the final vaccine performance metric v.
- ⁇ ⁇ is not necessarily a superset of ⁇ ⁇ .
- at Step 4 if a vaccine peptide set was found in Step 3, it is added to the vaccine peptide set design D. If an acceptable vaccine design ⁇ ⁇ was found in Step 4, the vaccine design set D is updated to consist of D ⁇ ⁇ ⁇ .
- design set D is returned as the final vaccine design. If not, the method returns to Step 1 and repeats all subsequent steps. [0587] In some embodiments, this procedure is repeated independently for each pathogen gene variant or target variant of interest, and the resulting independent vaccine sets can be merged into a combined vaccine. In some embodiments, this procedure is repeated independently for each single protein target of interest (e.g., influenza, cancer neoantigen, etc.), and the resulting independent vaccine sets can be merged into a combined vaccine. Methods for combining multiple vaccines [0588] The above-described methods will produce an optimized target peptide set (e.g., third peptide set) for one or more individual targets.
- target peptide set e.g., third peptide set
- a method for designing separate vaccines for MHC class I and class II-based immunity for multiple targets (e.g., two or more targets such as KRAS G12D and KRAS G12V).
- targets e.g., two or more targets such as KRAS G12D and KRAS G12V.
- a method is disclosed for producing a combined peptide vaccine for multiple targets by using a table of presentations for a disease that is based on - 111 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 empirical data from sources such as the Cancer Genome Atlas (TCGA).
- a method for producing a combined peptide vaccine for multiple strains of a pathogen (e.g., influenza) that is based on empirical data of strain prevalence where prevalence is used to represent the probability of the presentation of a given strain.
- a pathogen e.g., influenza
- the probabilities of each pathogen protein target are identical and sum to one.
- the probabilities of each pathogen protein target vary based on the observed or predicted immunogenicity of each protein (e.g., based on the expression of the pathogen protein or its processing).
- FIG.6 shows various embodiment for factoring in disease presentation type (e.g., pancreatic cancer, colorectal cancer, and skin cancer) by probability, for each disease presentation, of target presented for various mutation targets (e.g., KRAS G12D, KRAS G12V, and KRAS G12R).
- a presentation is a unique set of targets that are presented by one form of a disease (e.g., distinct type of cancer or cancer indication as shown in FIG.6).
- FIG.6 shows an example of the probability of that presentation, and the probability that a given target is observed.
- the method for multi-target vaccine design will allocate peptide resources for inducing disease immunity based on the presentation and respective target probabilities as shown in FIG.6, for example.
- presentations correspond to the prevalence of targets in different human populations or different risk groups.
- the probability of a target in a population is computed by summing for each possible presentation the probability of that presentation times the probability of the target in that presentation.
- FIG.6 shows weights used for merging individual vaccines for each target (row) into combined vaccines for each disease indication (column). Values indicate the observed fraction of cases containing each target mutation.
- Data are from The Cancer Genome Atlas (TCGA). For each disease indication, TCGA data are filtered to cases where the Primary Site is the indication.
- presentations are used to represent different strains of pathogens, where the probability of a presentation is based on the observed prevalence of a given pathogen strain.
- the probabilities of each pathogen protein target are identical and sum to one.
- the probabilities of each pathogen protein target vary based upon the observed or predicted immunogenicity of each pathogen protein (e.g., based on the expression of - 112 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 the pathogen protein or its processing).
- presentation probabilities are used to create a combined vaccine for more than one pathogen strain, where vaccines for each individual strain are combined using the prevalence probabilities of each strain.
- the immunogenic importance of each pathogen protein is considered by assigning different presentation probabilities to different pathogen proteins that are used as vaccine targets, and the resulting target specific vaccines are combined using these probabilities.
- the same vaccine design will be generated for mutations to different proteins when the base peptides generated by the mutations to the different proteins are identical.
- the following mutations have identical vaccine designs because they share the same set of base peptides: HRAS Q61K, NRAS Q61K, and KRAS Q61K; HRAS Q61L, NRAS Q61L, and KRAS Q61L; HRAS Q61R, NRAS Q61R, and KRAS Q61R.
- HRAS Q61K, NRAS Q61K, and KRAS Q61K the following mutations have identical vaccine designs because they share the same set of base peptides: HRAS Q61K, NRAS Q61K, and KRAS Q61K
- HRAS Q61L, NRAS Q61L, and KRAS Q61L HRAS Q61R, NRAS Q61R, and KRAS Q61R.
- FIG.6 in some embodiments when two mutations have identical individual vaccine designs their presentation specific probabilities are added when weighting the individual vaccine design for inclusion in a combined vaccine as described below (e.g., for Thyroid Cancer NRAS Q61R and HRAS Q61R
- the method first includes designing an individual peptide vaccine for each target to create a combined vaccine design for multiple targets. This initially results in sets of target-specific vaccine designs.
- the marginal predicted vaccine performance of each target-specific vaccine at size k is defined by predicted vaccine performance at size k minus the predicted vaccine performance of the vaccine at size k minus one (see FIGs.3-4).
- the composition of a vaccine may change as the number of peptides used in the vaccine increases, and thus for computing contributions to a combined vaccine the marginal predicted vaccine performance of each target-specific vaccine is used instead of a specific set of peptides.
- the weighted marginal predicted vaccine performance of a target-specific vaccine design for each target specific vaccine size is computed as shown in FIG. 8.
- its weighted predicted vaccine performance is computed by multiplying its predicted vaccine performance times the probability of the target in the population (e.g., by using values as shown in FIG.6).
- the marginal weighted predicted vaccine performance for a target specific vaccine is its weighted coverage at size k minus its coverage a size k minus one (e.g., see FIGs.3-4).
- the marginal weighted predicted vaccine performance of a target specific vaccine of size one is its weighted predicted vaccine - 113 - ActiveUS 205953775 Attorney Docket No.
- the marginal weighted predicted vaccine performances for all vaccines are combined into a single list, and the combined list is sorted from largest to least by the weighted marginal predicted vaccine performances of the target specific vaccines as shown in FIG.7.
- the combined vaccine of size n is then determined by the first n elements of this list.
- the peptides for the combined vaccine are determined by the individual peptide target vaccines whose sizes add to n and whose weighted predicted vaccine performances sums to the same sum as the first n elements of the sorted list. This maximizes the predicted vaccine performance of the combined vaccine of size n.
- the combined multiple target vaccine can be designed on its overall predicted coverage for the disease described depending on the presentation table used (e.g., see FIG.6), by its predicted coverage for a specific indication, and/or by its predicted coverage for a specific target by adjusting the weighting used for predicted vaccine performance accordingly.
- the peptides of the combined vaccine are determined by the contributions of target-specific designs. For example, if the combined vaccine includes a target-specific vaccine of size k, then the vaccine peptides for this target at size k are used in the combined vaccine.
- Table 1 (below) contains the peptides present in independent (single target) MHC class I vaccine designs.
- Table 2 (below) contains the contains the peptides present in independent (single target) MHC class II vaccine designs.
- the Sequence Listing provides heteroclitic peptides useful in MHC class I vaccines and MHC class II vaccines for the mutated proteins, specific protein mutations, and indications in Tables 1 and 2. Any subset of the individual/single target vaccines for MHC class I and class II can be combined to create a vaccine for two or more multiple targets.
- Combined Vaccine Design Procedure [0597] In some embodiments, the procedure described herein is used to combine individual compact vaccines optimized for different targets into a single optimized combined vaccine.
- the computational inputs for the procedure are: ⁇ : Set of neoantigen or pathogenic targets of interest (e.g., KRAS G12D, KRAS G12V, KRAS G12R) - 114 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 ⁇ : Vaccine sets optimized individually for each target. Let ⁇ ⁇ , ⁇ denote the optimal vaccine set of exactly k peptides for target t ⁇ ⁇ (e.g., as computed by the procedures describe above). Note that ⁇ ⁇ , ⁇ may not necessarily be a superset of ⁇ ⁇ , ⁇ .
- W ⁇ ⁇ [0,1] : Target weighting function mapping each target t ⁇ ⁇ to a probability or weight of t in a particular presentation of interest (e.g., pancreatic cancer; see FIG.6, for example).
- POPULATIONCOVERAGE ⁇ ⁇ [0,1]: Function mapping a peptide set into population coverage (e.g., EvalVax). This function may also take as input additional parameters, including HLA haplotype frequencies and a minimum per-individual number of peptide- HLA hits N (here, we compute coverage as P(n ⁇ 1) using EvalVax-Robust).
- Step 1 For each target t (individually) compute optimized vaccines of sizes 1 to m (1 to m peptides; m is the largest vaccine size used for the computation) as the sets ⁇ ⁇ , ⁇ where k denotes the size of the vaccine. Then, compute the vaccine performance for each vaccine size.
- ⁇ ⁇ , ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ , ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ , ⁇ ⁇ ⁇ ⁇ ⁇ , ⁇
- c t,k is generally monotonically increasing and concave down for increasing values of k (each additional peptide increases coverage but with decreasing returns).
- m t,k should be a monotonically decreasing function in k (by Step 1 above).
- the weighted marginal population coverage ⁇ ⁇ , ⁇ is computed using weights of each target in W: ⁇ - 115 - ActiveUS 205953775 Attorney Docket No.
- the weighted marginal population coverage gives the effective marginal coverage of the k-th peptide in the vaccine weighted by the prevalence of the target in the presentation (by multiplication with the probability/weight of the target in the presentation).
- the weighted vaccine performances are merged for all targets to produce combined vaccine designs at each peptide count.
- FIG.8 shows an example Python implementation of the MERGEMULTI function.
- This procedure takes as input multiple sorted (descending) lists and merges them into a single sorted (descending) list.
- M indicates the output of MERGEMULTI where each element Mk contains both the marginal weighted coverage and source (target) of the k-th peptide in the combined vaccine.
- the combined vaccine contains peptides from different targets.
- a vaccine with a desired performance is selected.
- the final vaccine size k can vary based upon the specific population coverage goals of the vaccine.
- the marginal weighted coverage values of the combined vaccine Mk can be cumulatively summed over k to give the overall effective (target-weighted) population coverage of the combined vaccine containing k peptides as ⁇ ⁇ (taking into account both the probabilities/weights of the targets in the presentation and the expected population coverage of peptides based on HLA display).
- the vaccine peptides corresponding to the target coverage is retrieved for the final vaccine size k.
- the optimal combined vaccine set ⁇ ⁇ ⁇ for the final vaccine size k is defined as: [0605]
- the combined vaccine with k peptides is the combination of the optimal individual (C t,k )-peptide vaccines.
- the final vaccine size k can vary based upon the specific population coverage goals of the vaccine.
- - 116 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 MHC class I peptide sequences
- a peptide composition (single target or combined multiple target) comprises about 1 to 40 MHC class I peptides with each peptide consisting of 8 or more amino acids.
- an MHC class I peptide composition is intended for one or more of the BRAF, CTNNB1, KRAS, PIK3CA, or TP53 mutated protein targets.
- an MHC class I peptide composition is intended for one or more of the BRAF G466V, CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, CTNNB1 T41I, KRAS A146T, KRAS A146V, KRAS Q61H, PIK3CA C420R, PIK3CA E453K, PIK3CA E545A, PIK3CA E726K, PIK3CA G118D, PIK3CA H1047L, PIK3CA N345K, PIK3CA Q546
- an MHC class I peptide composition is intended to prevent cancer. In some embodiments, an MHC class I peptide composition is intended to treat cancer. [0607] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the BRAF protein comprises one or more of the SEQ ID NOs: 1 to 16 and SEQ ID NO: 795.
- any one of the peptides in the BRAF composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16 or SEQ ID NO: 795.
- the amino acid sequence for a MHC class I peptide composition for mutation in the BRAF protein comprises one or more of the SEQ ID NOs: 1 to 16, SEQ ID NO: 795, and SEQ ID NOs: 1280 to 2625.
- any one of the peptides in the BRAF composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16, SEQ ID NO: 795, or SEQ ID NOs: 1280 to 2625.
- the amino acid sequence for a MHC class I peptide composition for mutation in the BRAF protein comprises two or more of the SEQ ID NOs: 1 to 16 and SEQ ID NO: 795.
- any one of the peptides in the BRAF - 117 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16 or SEQ ID NO: 795.
- the amino acid sequence for a MHC class I peptide composition for mutation in the BRAF protein comprises two or more of the SEQ ID NOs: 1 to 16, SEQ ID NO: 795, and SEQ ID NOs: 1280 to 2625.
- any one of the peptides in the BRAF composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16, SEQ ID NO: 795, or SEQ ID NOs: 1280 to 2625.
- the amino acid sequence for a MHC class I peptide composition for mutation in the CTNNB1 protein comprises one or more of the SEQ ID NOs: 17 to 184 and SEQ ID NOs: 796 to 801.
- any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 184 or SEQ ID NOs: 796 to 801.
- the amino acid sequence for a MHC class I peptide composition for mutation in the CTNNB1 protein comprises one or more of the SEQ ID NOs: 17 to 184, SEQ ID NOs: 796 to 801, and SEQ ID NOs: 2626 to 8516.
- any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 184, SEQ ID NOs: 796 to 801, or SEQ ID NOs: 2626 to 8516.
- the amino acid sequence for a MHC class I peptide composition for mutation in the CTNNB1 protein comprises two or more of the SEQ ID NOs: 17 to 184 and SEQ ID NOs: 796 to 801.
- any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 184 or SEQ ID NOs: 796 to 801.
- the amino acid sequence for a MHC class I peptide composition for mutation in the CTNNB1 protein comprises two or more of the SEQ ID NOs: 17 to 184, SEQ ID NOs: 796 to 801, and SEQ ID NOs: 2626 to 8516.
- any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, - 118 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for mutation in the KRAS protein comprises one or more of the SEQ ID NOs: 185 to 222 and SEQ ID NOs: 802 to 803.
- any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 222 or SEQ ID NOs: 802 to 803.
- the amino acid sequence for a MHC class I peptide composition for mutation in the KRAS protein comprises one or more of the SEQ ID NOs: 185 to 222, SEQ ID NOs: 802 to 803, and SEQ ID NOs: 8517 to 10266.
- any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 222, SEQ ID NOs: 802 to 803, or SEQ ID NOs: 8517 to 10266.
- the amino acid sequence for a MHC class I peptide composition for mutation in the KRAS protein comprises two or more of the SEQ ID NOs: 185 to 222 and SEQ ID NOs: 802 to 803.
- any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 222 or SEQ ID NOs: 802 to 803.
- the amino acid sequence for a MHC class I peptide composition for mutation in the KRAS protein comprises two or more of the SEQ ID NOs: 185 to 222, SEQ ID NOs: 802 to 803, and SEQ ID NOs: 8517 to 10266.
- any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 222, SEQ ID NOs: 802 to 803, or SEQ ID NOs: 8517 to 10266.
- the amino acid sequence for a MHC class I peptide composition for mutation in the PIK3CA protein comprises one or more of the SEQ ID NOs: 223 to 386 and SEQ ID NOs: 804 to 813.
- any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, - 119 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 386 or SEQ ID NOs: 804 to 813.
- the amino acid sequence for a MHC class I peptide composition for mutation in the PIK3CA protein comprises one or more of the SEQ ID NOs: 223 to 386, SEQ ID NOs: 804 to 813, and SEQ ID NOs: 10267 to 15528.
- any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 386, SEQ ID NOs: 804 to 813, or SEQ ID NOs: 10267 to 15528.
- the amino acid sequence for a MHC class I peptide composition for mutation in the PIK3CA protein comprises two or more of the SEQ ID NOs: 223 to 386 and SEQ ID NOs: 804 to 813.
- any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 386 or SEQ ID NOs: 804 to 813.
- the amino acid sequence for a MHC class I peptide composition for mutation in the PIK3CA protein comprises two or more of the SEQ ID NOs: 223 to 386, SEQ ID NOs: 804 to 813, and SEQ ID NOs: 10267 to 15528.
- any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 386, SEQ ID NOs: 804 to 813, or SEQ ID NOs: 10267 to 15528.
- the amino acid sequence for a MHC class I peptide composition for mutation in the TP53 protein comprises one or more of the SEQ ID NOs: 387 to 794 and SEQ ID NOs: 814 to 834.
- any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 794 or SEQ ID NOs: 814 to 834.
- the amino acid sequence for a MHC class I peptide composition for mutation in the TP53 protein comprises one or more of the SEQ ID NOs: 387 to 794, SEQ ID NOs: 814 to 834, and SEQ ID NOs: 15529 to 36796.
- any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, - 120 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 794, SEQ ID NOs: 814 to 834, or SEQ ID NOs: 15529 to 36796.
- the amino acid sequence for a MHC class I peptide composition for mutation in the TP53 protein comprises two or more of the SEQ ID NOs: 387 to 794 and SEQ ID NOs: 814 to 834.
- any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 794 or SEQ ID NOs: 814 to 834.
- the amino acid sequence for a MHC class I peptide composition for mutation in the TP53 protein comprises two or more of the SEQ ID NOs: 387 to 794, SEQ ID NOs: 814 to 834, and SEQ ID NOs: 15529 to 36796.
- any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 794, SEQ ID NOs: 814 to 834, or SEQ ID NOs: 15529 to 36796.
- the amino acid sequence for a MHC class I peptide composition for the BRAF G466V protein mutation comprises one or more of the SEQ ID NOs: 1 to 16 and SEQ ID NO: 795.
- any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16 or SEQ ID NO: 795.
- the amino acid sequence for a MHC class I peptide composition for the BRAF G466V protein mutation comprises one or more of the SEQ ID NOs: 1 to 16, SEQ ID NO: 795, and SEQ ID NOs: 1280 to 2625.
- any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16, SEQ ID NO: 795, or SEQ ID NOs: 1280 to 2625.
- the amino acid sequence for a MHC class I peptide composition for the BRAF G466V protein mutation comprises two or more of the SEQ ID NOs: 1 to 16 and SEQ ID NO: 795.
- any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16 or SEQ ID NO: 795.
- the amino acid sequence for a MHC class I peptide composition for the BRAF G466V protein mutation comprises two or more of the SEQ ID NOs: - 121 - ActiveUS 205953775 Attorney Docket No.
- any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16, SEQ ID NO: 795, or SEQ ID NOs: 1280 to 2625.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 D32G protein mutation comprises one or more of the SEQ ID NOs: 17 to 36.
- any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 36.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 D32G protein mutation comprises one or more of the SEQ ID NOs: 17 to 36 and SEQ ID NOs: 2626 to 3063.
- any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 36 or SEQ ID NOs: 2626 to 3063.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 D32G protein mutation comprises two or more of the SEQ ID NOs: 17 to 36.
- any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 36.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 D32G protein mutation comprises two or more of the SEQ ID NOs: 17 to 36 and SEQ ID NOs: 2626 to 3063.
- any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 36 or SEQ ID NOs: 2626 to 3063.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 G34E protein mutation comprises one or more of the SEQ ID NOs: 37 to 52.
- any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 37 to 52.
- - 122 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 G34E protein mutation comprises one or more of the SEQ ID NOs: 37 to 52 and SEQ ID NOs: 3064 to 3582.
- any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 37 to 52 or SEQ ID NOs: 3064 to 3582.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 G34E protein mutation comprises two or more of the SEQ ID NOs: 37 to 52.
- any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 37 to 52.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 G34E protein mutation comprises two or more of the SEQ ID NOs: 37 to 52 and SEQ ID NOs: 3064 to 3582.
- any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 37 to 52 or SEQ ID NOs: 3064 to 3582.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33C protein mutation comprises one or more of the SEQ ID NOs: 53 to 67.
- any one of the peptides in the CTNNB1 S33C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 53 to 67.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33C protein mutation comprises one or more of the SEQ ID NOs: 53 to 67 and SEQ ID NOs: 3583 to 3914.
- any one of the peptides in the CTNNB1 S33C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 53 to 67 or SEQ ID NOs: 3583 to 3914.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33C protein mutation comprises two or more of the SEQ ID NOs: 53 to 67.
- any one of the peptides in the CTNNB1 S33C - 123 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 53 to 67.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33C protein mutation comprises two or more of the SEQ ID NOs: 53 to 67 and SEQ ID NOs: 3583 to 3914.
- any one of the peptides in the CTNNB1 S33C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 53 to 67 or SEQ ID NOs: 3583 to 3914.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33F protein mutation comprises one or more of the SEQ ID NOs: 68 to 86.
- any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 68 to 86.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33F protein mutation comprises one or more of the SEQ ID NOs: 68 to 86 and SEQ ID NOs: 3915 to 4542.
- any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 68 to 86 or SEQ ID NOs: 3915 to 4542.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33F protein mutation comprises two or more of the SEQ ID NOs: 68 to 86.
- any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 68 to 86.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33F protein mutation comprises two or more of the SEQ ID NOs: 68 to 86 and SEQ ID NOs: 3915 to 4542.
- any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 68 to 86 or SEQ ID NOs: 3915 to 4542.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37C protein mutation comprises one or more of the SEQ ID NOs: 87 to 102 and SEQ ID NO: 796.
- any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 87 to 102 or SEQ ID NO: 796.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37C protein mutation comprises one or more of the SEQ ID NOs: 87 to 102, SEQ ID NO: 796, and SEQ ID NOs: 4543 to 5000.
- any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 87 to 102, SEQ ID NO: 796, or SEQ ID NOs: 4543 to 5000.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37C protein mutation comprises two or more of the SEQ ID NOs: 87 to 102 and SEQ ID NO: 796.
- any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 87 to 102 or SEQ ID NO: 796.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37C protein mutation comprises two or more of the SEQ ID NOs: 87 to 102, SEQ ID NO: 796, and SEQ ID NOs: 4543 to 5000.
- any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 87 to 102, SEQ ID NO: 796, or SEQ ID NOs: 4543 to 5000.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37F protein mutation comprises one or more of the SEQ ID NOs: 103 to 119.
- any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 103 to 119.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37F protein mutation comprises one or more of the SEQ ID - 125 - ActiveUS 205953775 Attorney Docket No.
- any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 103 to 119 or SEQ ID NOs: 5001 to 5916.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37F protein mutation comprises two or more of the SEQ ID NOs: 103 to 119.
- any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 103 to 119.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37F protein mutation comprises two or more of the SEQ ID NOs: 103 to 119 and SEQ ID NOs: 5001 to 5916.
- any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 103 to 119 or SEQ ID NOs: 5001 to 5916.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45F protein mutation comprises one or more of the SEQ ID NOs: 120 to 134 and SEQ ID NO: 797.
- any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 120 to 134 or SEQ ID NO: 797.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45F protein mutation comprises one or more of the SEQ ID NOs: 120 to 134, SEQ ID NO: 797, and SEQ ID NOs: 5917 to 6394.
- any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 120 to 134, SEQ ID NO: 797, or SEQ ID NOs: 5917 to 6394.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45F protein mutation comprises two or more of the SEQ ID NOs: 120 to 134 and SEQ ID NO: 797.
- any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, - 126 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 120 to 134 or SEQ ID NO: 797.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45F protein mutation comprises two or more of the SEQ ID NOs: 120 to 134, SEQ ID NO: 797, and SEQ ID NOs: 5917 to 6394.
- any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 120 to 134, SEQ ID NO: 797, or SEQ ID NOs: 5917 to 6394.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45P protein mutation comprises one or more of the SEQ ID NOs: 135 to 150 and SEQ ID NO: 798.
- any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 135 to 150 or SEQ ID NO: 798.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45P protein mutation comprises one or more of the SEQ ID NOs: 135 to 150, SEQ ID NO: 798, and SEQ ID NOs: 6395 to 7051.
- any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 135 to 150, SEQ ID NO: 798, or SEQ ID NOs: 6395 to 7051.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45P protein mutation comprises two or more of the SEQ ID NOs: 135 to 150 and SEQ ID NO: 798.
- any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 135 to 150 or SEQ ID NO: 798.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45P protein mutation comprises two or more of the SEQ ID NOs: 135 to 150, SEQ ID NO: 798, and SEQ ID NOs: 6395 to 7051.
- any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, - 127 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 135 to 150, SEQ ID NO: 798, or SEQ ID NOs: 6395 to 7051.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41A protein mutation comprises one or more of the SEQ ID NOs: 151 to 167 and SEQ ID NOs: 799 to 800.
- any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 151 to 167 or SEQ ID NOs: 799 to 800.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41A protein mutation comprises one or more of the SEQ ID NOs: 151 to 167, SEQ ID NOs: 799 to 800, and SEQ ID NOs: 7052 to 7846.
- any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 151 to 167, SEQ ID NOs: 799 to 800, or SEQ ID NOs: 7052 to 7846.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41A protein mutation comprises two or more of the SEQ ID NOs: 151 to 167 and SEQ ID NOs: 799 to 800.
- any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 151 to 167 or SEQ ID NOs: 799 to 800.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41A protein mutation comprises two or more of the SEQ ID NOs: 151 to 167, SEQ ID NOs: 799 to 800, and SEQ ID NOs: 7052 to 7846.
- any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 151 to 167, SEQ ID NOs: 799 to 800, or SEQ ID NOs: 7052 to 7846.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41I protein mutation comprises one or more of the SEQ ID NOs: 168 to 184 and SEQ ID NO: 801.
- any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, - 128 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 168 to 184 or SEQ ID NO: 801.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41I protein mutation comprises one or more of the SEQ ID NOs: 168 to 184, SEQ ID NO: 801, and SEQ ID NOs: 7847 to 8516.
- any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 168 to 184, SEQ ID NO: 801, or SEQ ID NOs: 7847 to 8516.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41I protein mutation comprises two or more of the SEQ ID NOs: 168 to 184 and SEQ ID NO: 801.
- any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 168 to 184 or SEQ ID NO: 801.
- the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41I protein mutation comprises two or more of the SEQ ID NOs: 168 to 184, SEQ ID NO: 801, and SEQ ID NOs: 7847 to 8516.
- any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 168 to 184, SEQ ID NO: 801, or SEQ ID NOs: 7847 to 8516.
- the amino acid sequence for a MHC class I peptide composition for the KRAS A146T protein mutation comprises one or more of the SEQ ID NOs: 185 to 193 and SEQ ID NO: 802.
- any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 193 or SEQ ID NO: 802.
- the amino acid sequence for a MHC class I peptide composition for the KRAS A146T protein mutation comprises one or more of the SEQ ID NOs: 185 to 193, SEQ ID NO: 802, and SEQ ID NOs: 8517 to 8904.
- any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 193, SEQ ID NO: 802, or SEQ ID NOs: 8517 to 8904.
- - 129 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the KRAS A146T protein mutation comprises two or more of the SEQ ID NOs: 185 to 193 and SEQ ID NO: 802.
- any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 193 or SEQ ID NO: 802.
- the amino acid sequence for a MHC class I peptide composition for the KRAS A146T protein mutation comprises two or more of the SEQ ID NOs: 185 to 193, SEQ ID NO: 802, and SEQ ID NOs: 8517 to 8904.
- any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 193, SEQ ID NO: 802, or SEQ ID NOs: 8517 to 8904.
- the amino acid sequence for a MHC class I peptide composition for the KRAS A146V protein mutation comprises one or more of the SEQ ID NOs: 194 to 202 and SEQ ID NO: 803.
- any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 194 to 202 or SEQ ID NO: 803.
- the amino acid sequence for a MHC class I peptide composition for the KRAS A146V protein mutation comprises one or more of the SEQ ID NOs: 194 to 202, SEQ ID NO: 803, and SEQ ID NOs: 8905 to 9308.
- any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 194 to 202, SEQ ID NO: 803, or SEQ ID NOs: 8905 to 9308.
- the amino acid sequence for a MHC class I peptide composition for the KRAS A146V protein mutation comprises two or more of the SEQ ID NOs: 194 to 202 and SEQ ID NO: 803.
- any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 194 to 202 or SEQ ID NO: 803.
- the amino acid sequence for a MHC class I peptide composition for the KRAS A146V protein mutation comprises two or more of the SEQ ID NOs: 194 to 202, SEQ ID NO: 803, and SEQ ID NOs: 8905 to 9308.
- any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, - 130 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the KRAS Q61H protein mutation comprises one or more of the SEQ ID NOs: 203 to 222.
- any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 203 to 222.
- the amino acid sequence for a MHC class I peptide composition for the KRAS Q61H protein mutation comprises one or more of the SEQ ID NOs: 203 to 222 and SEQ ID NOs: 9309 to 10266.
- any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 203 to 222 or SEQ ID NOs: 9309 to 10266.
- the amino acid sequence for a MHC class I peptide composition for the KRAS Q61H protein mutation comprises two or more of the SEQ ID NOs: 203 to 222.
- any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 203 to 222.
- the amino acid sequence for a MHC class I peptide composition for the KRAS Q61H protein mutation comprises two or more of the SEQ ID NOs: 203 to 222 and SEQ ID NOs: 9309 to 10266.
- any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 203 to 222 or SEQ ID NOs: 9309 to 10266.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA C420R protein mutation comprises one or more of the SEQ ID NOs: 223 to 239 and SEQ ID NOs: 804 to 805.
- any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 239 or SEQ ID NOs: 804 to 805.
- - 131 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA C420R protein mutation comprises one or more of the SEQ ID NOs: 223 to 239, SEQ ID NOs: 804 to 805, and SEQ ID NOs: 10267 to 10781.
- any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 239, SEQ ID NOs: 804 to 805, or SEQ ID NOs: 10267 to 10781.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA C420R protein mutation comprises two or more of the SEQ ID NOs: 223 to 239 and SEQ ID NOs: 804 to 805.
- any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 239 or SEQ ID NOs: 804 to 805.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA C420R protein mutation comprises two or more of the SEQ ID NOs: 223 to 239, SEQ ID NOs: 804 to 805, and SEQ ID NOs: 10267 to 10781.
- any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 239, SEQ ID NOs: 804 to 805, or SEQ ID NOs: 10267 to 10781.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E453K protein mutation comprises one or more of the SEQ ID NOs: 240 to 255 and SEQ ID NOs: 806 to 807.
- any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 240 to 255 or SEQ ID NOs: 806 to 807.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E453K protein mutation comprises one or more of the SEQ ID NOs: 240 to 255, SEQ ID NOs: 806 to 807, and SEQ ID NOs: 10782 to 11260.
- any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 132 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 identical to SEQ ID NOs: 240 to 255, SEQ ID NOs: 806 to 807, or SEQ ID NOs: 10782 to 11260.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E453K protein mutation comprises two or more of the SEQ ID NOs: 240 to 255 and SEQ ID NOs: 806 to 807.
- any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 240 to 255 or SEQ ID NOs: 806 to 807.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E453K protein mutation comprises two or more of the SEQ ID NOs: 240 to 255, SEQ ID NOs: 806 to 807, and SEQ ID NOs: 10782 to 11260.
- any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 240 to 255, SEQ ID NOs: 806 to 807, or SEQ ID NOs: 10782 to 11260.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E545A protein mutation comprises one or more of the SEQ ID NOs: 256 to 271 and SEQ ID NO: 808.
- any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 256 to 271 or SEQ ID NO: 808.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E545A protein mutation comprises one or more of the SEQ ID NOs: 256 to 271, SEQ ID NO: 808, and SEQ ID NOs: 11261 to 11604.
- any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 256 to 271, SEQ ID NO: 808, or SEQ ID NOs: 11261 to 11604.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E545A protein mutation comprises two or more of the SEQ ID NOs: 256 to 271 and SEQ ID NO: 808.
- any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, - 133 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 256 to 271 or SEQ ID NO: 808.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E545A protein mutation comprises two or more of the SEQ ID NOs: 256 to 271, SEQ ID NO: 808, and SEQ ID NOs: 11261 to 11604.
- any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 256 to 271, SEQ ID NO: 808, or SEQ ID NOs: 11261 to 11604.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E726K protein mutation comprises one or more of the SEQ ID NOs: 272 to 290 and SEQ ID NO: 809.
- any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 272 to 290 or SEQ ID NO: 809.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E726K protein mutation comprises one or more of the SEQ ID NOs: 272 to 290, SEQ ID NO: 809, and SEQ ID NOs: 11605 to 12160.
- any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 272 to 290, SEQ ID NO: 809, or SEQ ID NOs: 11605 to 12160.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E726K protein mutation comprises two or more of the SEQ ID NOs: 272 to 290 and SEQ ID NO: 809.
- any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 272 to 290 or SEQ ID NO: 809.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA E726K protein mutation comprises two or more of the SEQ ID NOs: 272 to 290, SEQ ID NO: 809, and SEQ ID NOs: 11605 to 12160.
- any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence - 134 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 272 to 290, SEQ ID NO: 809, or SEQ ID NOs: 11605 to 12160.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA G118D protein mutation comprises one or more of the SEQ ID NOs: 291 to 307.
- any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 291 to 307.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA G118D protein mutation comprises one or more of the SEQ ID NOs: 291 to 307 and SEQ ID NOs: 12161 to 12944.
- any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 291 to 307 or SEQ ID NOs: 12161 to 12944.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA G118D protein mutation comprises two or more of the SEQ ID NOs: 291 to 307.
- any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 291 to 307.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA G118D protein mutation comprises two or more of the SEQ ID NOs: 291 to 307 and SEQ ID NOs: 12161 to 12944.
- any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 291 to 307 or SEQ ID NOs: 12161 to 12944.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA H1047L protein mutation comprises one or more of the SEQ ID NOs: 308 to 325.
- any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 308 to 325.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA H1047L protein mutation comprises one or more of the SEQ ID - 135 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 NOs: 308 to 325 and SEQ ID NOs: 12945 to 13568.
- any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 308 to 325 or SEQ ID NOs: 12945 to 13568.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA H1047L protein mutation comprises two or more of the SEQ ID NOs: 308 to 325.
- any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 308 to 325.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA H1047L protein mutation comprises two or more of the SEQ ID NOs: 308 to 325 and SEQ ID NOs: 12945 to 13568.
- any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 308 to 325 or SEQ ID NOs: 12945 to 13568.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA N345K protein mutation comprises one or more of the SEQ ID NOs: 326 to 339 and SEQ ID NOs: 810 to 811.
- any one of the peptides in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 326 to 339 or SEQ ID NOs: 810 to 811.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA N345K protein mutation comprises one or more of the SEQ ID NOs: 326 to 339, SEQ ID NOs: 810 to 811, and SEQ ID NOs: 13569 to 13997.
- any one of the peptides in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 326 to 339, SEQ ID NOs: 810 to 811, or SEQ ID NOs: 13569 to 13997.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA N345K protein mutation comprises two or more of the SEQ ID NOs: 326 to 339 and SEQ ID NOs: 810 to 811.
- any one of the peptides - 136 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA N345K protein mutation comprises two or more of the SEQ ID NOs: 326 to 339, SEQ ID NOs: 810 to 811, and SEQ ID NOs: 13569 to 13997.
- any one of the peptides in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 326 to 339, SEQ ID NOs: 810 to 811, or SEQ ID NOs: 13569 to 13997.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546K protein mutation comprises one or more of the SEQ ID NOs: 340 to 358 and SEQ ID NO: 812.
- any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 340 to 358 or SEQ ID NO: 812.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546K protein mutation comprises one or more of the SEQ ID NOs: 340 to 358, SEQ ID NO: 812, and SEQ ID NOs: 13998 to 14491.
- any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 340 to 358, SEQ ID NO: 812, or SEQ ID NOs: 13998 to 14491.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546K protein mutation comprises two or more of the SEQ ID NOs: 340 to 358 and SEQ ID NO: 812.
- any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 340 to 358 or SEQ ID NO: 812.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546K protein mutation comprises two or more of the SEQ ID NOs: 340 to 358, SEQ ID NO: 812, and SEQ ID NOs: 13998 to 14491.
- any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 340 to 358, SEQ ID NO: 812, or SEQ ID NOs: 13998 to 14491.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546R protein mutation comprises one or more of the SEQ ID NOs: 359 to 376 and SEQ ID NO: 813.
- any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 359 to 376 or SEQ ID NO: 813.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546R protein mutation comprises one or more of the SEQ ID NOs: 359 to 376, SEQ ID NO: 813, and SEQ ID NOs: 14492 to 15002.
- any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 359 to 376, SEQ ID NO: 813, or SEQ ID NOs: 14492 to 15002. [0717]
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546R protein mutation comprises two or more of the SEQ ID NOs: 359 to 376 and SEQ ID NO: 813.
- any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 359 to 376 or SEQ ID NO: 813.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546R protein mutation comprises two or more of the SEQ ID NOs: 359 to 376, SEQ ID NO: 813, and SEQ ID NOs: 14492 to 15002.
- any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 359 to 376, SEQ ID NO: 813, or SEQ ID NOs: 14492 to 15002. [0719]
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA R108H protein mutation comprises one or more of the SEQ ID NOs: 377 to 386.
- any one of the peptides in the PIK3CA R108H - 138 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 377 to 386.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA R108H protein mutation comprises one or more of the SEQ ID NOs: 377 to 386 and SEQ ID NOs: 15003 to 15528.
- any one of the peptides in the PIK3CA R108H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 377 to 386 or SEQ ID NOs: 15003 to 15528.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA R108H protein mutation comprises two or more of the SEQ ID NOs: 377 to 386.
- any one of the peptides in the PIK3CA R108H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 377 to 386.
- the amino acid sequence for a MHC class I peptide composition for the PIK3CA R108H protein mutation comprises two or more of the SEQ ID NOs: 377 to 386 and SEQ ID NOs: 15003 to 15528.
- any one of the peptides in the PIK3CA R108H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 377 to 386 or SEQ ID NOs: 15003 to 15528.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C176F protein mutation comprises one or more of the SEQ ID NOs: 387 to 403 and SEQ ID NOs: 814 to 815.
- any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 403 or SEQ ID NOs: 814 to 815.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C176F protein mutation comprises one or more of the SEQ ID NOs: 387 to 403, SEQ ID NOs: 814 to 815, and SEQ ID NOs: 15529 to 16093.
- any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 139 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C176F protein mutation comprises two or more of the SEQ ID NOs: 387 to 403 and SEQ ID NOs: 814 to 815.
- any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 403 or SEQ ID NOs: 814 to 815.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C176F protein mutation comprises two or more of the SEQ ID NOs: 387 to 403, SEQ ID NOs: 814 to 815, and SEQ ID NOs: 15529 to 16093.
- any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 403, SEQ ID NOs: 814 to 815, or SEQ ID NOs: 15529 to 16093.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C176Y protein mutation comprises one or more of the SEQ ID NOs: 404 to 420 and SEQ ID NO: 816.
- any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 404 to 420 or SEQ ID NO: 816.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C176Y protein mutation comprises one or more of the SEQ ID NOs: 404 to 420, SEQ ID NO: 816, and SEQ ID NOs: 16094 to 16634.
- any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 404 to 420, SEQ ID NO: 816, or SEQ ID NOs: 16094 to 16634.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C176Y protein mutation comprises two or more of the SEQ ID NOs: 404 to 420 and SEQ ID NO: 816.
- any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 404 to 420 or SEQ ID NO: 816.
- - 140 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C176Y protein mutation comprises two or more of the SEQ ID NOs: 404 to 420, SEQ ID NO: 816, and SEQ ID NOs: 16094 to 16634.
- any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 404 to 420, SEQ ID NO: 816, or SEQ ID NOs: 16094 to 16634.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C238Y protein mutation comprises one or more of the SEQ ID NOs: 421 to 440.
- any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 421 to 440.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C238Y protein mutation comprises one or more of the SEQ ID NOs: 421 to 440 and SEQ ID NOs: 16635 to 17413.
- any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 421 to 440 or SEQ ID NOs: 16635 to 17413.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C238Y protein mutation comprises two or more of the SEQ ID NOs: 421 to 440.
- any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 421 to 440.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C238Y protein mutation comprises two or more of the SEQ ID NOs: 421 to 440 and SEQ ID NOs: 16635 to 17413.
- any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 421 to 440 or SEQ ID NOs: 16635 to 17413.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C275Y protein mutation comprises one or more of the SEQ ID NOs: 441 to 457.
- any one of the peptides in the TP53 C275Y composition - 141 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 441 to 457.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C275Y protein mutation comprises one or more of the SEQ ID NOs: 441 to 457 and SEQ ID NOs: 17414 to 18100.
- any one of the peptides in the TP53 C275Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 441 to 457 or SEQ ID NOs: 17414 to 18100.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C275Y protein mutation comprises two or more of the SEQ ID NOs: 441 to 457.
- any one of the peptides in the TP53 C275Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 441 to 457.
- the amino acid sequence for a MHC class I peptide composition for the TP53 C275Y protein mutation comprises two or more of the SEQ ID NOs: 441 to 457 and SEQ ID NOs: 17414 to 18100.
- any one of the peptides in the TP53 C275Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 441 to 457 or SEQ ID NOs: 17414 to 18100.
- the amino acid sequence for a MHC class I peptide composition for the TP53 E285K protein mutation comprises one or more of the SEQ ID NOs: 458 to 473 and SEQ ID NOs: 817 to 818.
- any one of the peptides in the TP53 E285K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 458 to 473 or SEQ ID NOs: 817 to 818.
- the amino acid sequence for a MHC class I peptide composition for the TP53 E285K protein mutation comprises one or more of the SEQ ID NOs: 458 to 473, SEQ ID NOs: 817 to 818, and SEQ ID NOs: 18101 to 18739.
- any one of the peptides in the TP53 E285K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 142 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the TP53 E285K protein mutation comprises two or more of the SEQ ID NOs: 458 to 473 and SEQ ID NOs: 817 to 818.
- any one of the peptides in the TP53 E285K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 458 to 473 or SEQ ID NOs: 817 to 818.
- the amino acid sequence for a MHC class I peptide composition for the TP53 E285K protein mutation comprises two or more of the SEQ ID NOs: 458 to 473, SEQ ID NOs: 817 to 818, and SEQ ID NOs: 18101 to 18739.
- any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 474 to 492.
- the amino acid sequence for a MHC class I peptide composition for the TP53 G245S protein mutation comprises one or more of the SEQ ID NOs: 474 to 492 and SEQ ID NOs: 18740 to 19567.
- any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 474 to 492 or SEQ ID NOs: 18740 to 19567.
- the amino acid sequence for a MHC class I peptide composition for the TP53 G245S protein mutation comprises two or more of the SEQ ID NOs: 474 to 492.
- any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 474 to 492.
- - 143 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the TP53 G245S protein mutation comprises two or more of the SEQ ID NOs: 474 to 492 and SEQ ID NOs: 18740 to 19567.
- any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 474 to 492 or SEQ ID NOs: 18740 to 19567.
- the amino acid sequence for a MHC class I peptide composition for the TP53 G245V protein mutation comprises one or more of the SEQ ID NOs: 493 to 511.
- any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 493 to 511.
- the amino acid sequence for a MHC class I peptide composition for the TP53 G245V protein mutation comprises one or more of the SEQ ID NOs: 493 to 511 and SEQ ID NOs: 19568 to 20400.
- any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 493 to 511 or SEQ ID NOs: 19568 to 20400.
- the amino acid sequence for a MHC class I peptide composition for the TP53 G245V protein mutation comprises two or more of the SEQ ID NOs: 493 to 511.
- any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 493 to 511.
- the amino acid sequence for a MHC class I peptide composition for the TP53 G245V protein mutation comprises two or more of the SEQ ID NOs: 493 to 511 and SEQ ID NOs: 19568 to 20400.
- any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 493 to 511 or SEQ ID NOs: 19568 to 20400.
- the amino acid sequence for a MHC class I peptide composition for the TP53 H179Y protein mutation comprises one or more of the SEQ ID NOs: 512 to 529 and SEQ ID NOs: 819 to 820.
- the amino acid sequence for a MHC class I peptide composition for the TP53 H179Y protein mutation comprises one or more of the SEQ ID NOs: 512 to 529, SEQ ID NOs: 819 to 820, and SEQ ID NOs: 20401 to 20880.
- any one of the peptides in the TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 512 to 529, SEQ ID NOs: 819 to 820, or SEQ ID NOs: 20401 to 20880.
- the amino acid sequence for a MHC class I peptide composition for the TP53 H179Y protein mutation comprises two or more of the SEQ ID NOs: 512 to 529 and SEQ ID NOs: 819 to 820.
- any one of the peptides in the TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 512 to 529 or SEQ ID NOs: 819 to 820.
- the amino acid sequence for a MHC class I peptide composition for the TP53 H179Y protein mutation comprises two or more of the SEQ ID NOs: 512 to 529, SEQ ID NOs: 819 to 820, and SEQ ID NOs: 20401 to 20880.
- any one of the peptides in the TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 512 to 529, SEQ ID NOs: 819 to 820, or SEQ ID NOs: 20401 to 20880.
- the amino acid sequence for a MHC class I peptide composition for the TP53 H193R protein mutation comprises one or more of the SEQ ID NOs: 530 to 546.
- any one of the peptides in the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 530 to 546.
- the amino acid sequence for a MHC class I peptide composition for the TP53 H193R protein mutation comprises one or more of the SEQ ID NOs: 530 to 546 and SEQ ID NOs: 20881 to 21921.
- any one of the peptides in - 145 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 530 to 546 or SEQ ID NOs: 20881 to 21921.
- the amino acid sequence for a MHC class I peptide composition for the TP53 H193R protein mutation comprises two or more of the SEQ ID NOs: 530 to 546.
- any one of the peptides in the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 530 to 546.
- the amino acid sequence for a MHC class I peptide composition for the TP53 H193R protein mutation comprises two or more of the SEQ ID NOs: 530 to 546 and SEQ ID NOs: 20881 to 21921.
- any one of the peptides in the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 530 to 546 or SEQ ID NOs: 20881 to 21921.
- the amino acid sequence for a MHC class I peptide composition for the TP53 I195T protein mutation comprises one or more of the SEQ ID NOs: 547 to 563 and SEQ ID NO: 821.
- any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 547 to 563 or SEQ ID NO: 821.
- the amino acid sequence for a MHC class I peptide composition for the TP53 I195T protein mutation comprises one or more of the SEQ ID NOs: 547 to 563, SEQ ID NO: 821, and SEQ ID NOs: 21922 to 22738.
- any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 547 to 563, SEQ ID NO: 821, or SEQ ID NOs: 21922 to 22738.
- the amino acid sequence for a MHC class I peptide composition for the TP53 I195T protein mutation comprises two or more of the SEQ ID NOs: 547 to 563 and SEQ ID NO: 821.
- any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 547 to 563 or SEQ ID NO: 821.
- - 146 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the TP53 I195T protein mutation comprises two or more of the SEQ ID NOs: 547 to 563, SEQ ID NO: 821, and SEQ ID NOs: 21922 to 22738.
- any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 547 to 563, SEQ ID NO: 821, or SEQ ID NOs: 21922 to 22738.
- the amino acid sequence for a MHC class I peptide composition for the TP53 K132E protein mutation comprises one or more of the SEQ ID NOs: 564 to 582 and SEQ ID NO: 822.
- any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 564 to 582 or SEQ ID NO: 822.
- the amino acid sequence for a MHC class I peptide composition for the TP53 K132E protein mutation comprises one or more of the SEQ ID NOs: 564 to 582, SEQ ID NO: 822, and SEQ ID NOs: 22739 to 24317.
- any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 564 to 582, SEQ ID NO: 822, or SEQ ID NOs: 22739 to 24317.
- the amino acid sequence for a MHC class I peptide composition for the TP53 K132E protein mutation comprises two or more of the SEQ ID NOs: 564 to 582 and SEQ ID NO: 822.
- any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 564 to 582 or SEQ ID NO: 822.
- the amino acid sequence for a MHC class I peptide composition for the TP53 K132E protein mutation comprises two or more of the SEQ ID NOs: 564 to 582, SEQ ID NO: 822, and SEQ ID NOs: 22739 to 24317.
- any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 564 to 582, SEQ ID NO: 822, or SEQ ID NOs: 22739 to 24317.
- the amino acid sequence for a MHC class I peptide composition for the TP53 K132N protein mutation comprises one or more of the SEQ ID NOs: 583 to 599 and SEQ ID NOs: 823 to 824.
- any one of the peptides in the - 147 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 583 to 599 or SEQ ID NOs: 823 to 824.
- the amino acid sequence for a MHC class I peptide composition for the TP53 K132N protein mutation comprises one or more of the SEQ ID NOs: 583 to 599, SEQ ID NOs: 823 to 824, and SEQ ID NOs: 24318 to 25729.
- any one of the peptides in the TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 583 to 599, SEQ ID NOs: 823 to 824, or SEQ ID NOs: 24318 to 25729.
- the amino acid sequence for a MHC class I peptide composition for the TP53 K132N protein mutation comprises two or more of the SEQ ID NOs: 583 to 599 and SEQ ID NOs: 823 to 824.
- any one of the peptides in the TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 583 to 599 or SEQ ID NOs: 823 to 824.
- the amino acid sequence for a MHC class I peptide composition for the TP53 K132N protein mutation comprises two or more of the SEQ ID NOs: 583 to 599, SEQ ID NOs: 823 to 824, and SEQ ID NOs: 24318 to 25729.
- any one of the peptides in the TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 583 to 599, SEQ ID NOs: 823 to 824, or SEQ ID NOs: 24318 to 25729.
- the amino acid sequence for a MHC class I peptide composition for the TP53 P151S protein mutation comprises one or more of the SEQ ID NOs: 600 to 614 and SEQ ID NOs: 825 to 826.
- any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 600 to 614, SEQ ID NOs: 825 to 826, or SEQ ID NOs: 25730 to 26739.
- the amino acid sequence for a MHC class I peptide composition for the TP53 P151S protein mutation comprises two or more of the SEQ ID NOs: 600 to 614 and SEQ ID NOs: 825 to 826.
- any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 600 to 614 or SEQ ID NOs: 825 to 826.
- the amino acid sequence for a MHC class I peptide composition for the TP53 P151S protein mutation comprises two or more of the SEQ ID NOs: 600 to 614, SEQ ID NOs: 825 to 826, and SEQ ID NOs: 25730 to 26739.
- any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 600 to 614, SEQ ID NOs: 825 to 826, or SEQ ID NOs: 25730 to 26739.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R213L protein mutation comprises one or more of the SEQ ID NOs: 615 to 631 and SEQ ID NOs: 827 to 828.
- any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 615 to 631 or SEQ ID NOs: 827 to 828.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R213L protein mutation comprises one or more of the SEQ ID NOs: 615 to 631, SEQ ID NOs: 827 to 828, and SEQ ID NOs: 26740 to 27926.
- any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 615 to 631, SEQ ID NOs: 827 to 828, or SEQ ID NOs: 26740 to 27926.
- - 149 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R213L protein mutation comprises two or more of the SEQ ID NOs: 615 to 631 and SEQ ID NOs: 827 to 828.
- any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 615 to 631 or SEQ ID NOs: 827 to 828.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R213L protein mutation comprises two or more of the SEQ ID NOs: 615 to 631, SEQ ID NOs: 827 to 828, and SEQ ID NOs: 26740 to 27926.
- any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 615 to 631, SEQ ID NOs: 827 to 828, or SEQ ID NOs: 26740 to 27926.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R249M protein mutation comprises one or more of the SEQ ID NOs: 632 to 648 and SEQ ID NO: 829.
- any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 632 to 648 or SEQ ID NO: 829.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R249M protein mutation comprises one or more of the SEQ ID NOs: 632 to 648, SEQ ID NO: 829, and SEQ ID NOs: 27927 to 29616.
- any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 632 to 648, SEQ ID NO: 829, or SEQ ID NOs: 27927 to 29616.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R249M protein mutation comprises two or more of the SEQ ID NOs: 632 to 648 and SEQ ID NO: 829.
- any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 632 to 648 or SEQ ID NO: 829.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R249M protein mutation comprises two or more of the SEQ ID NOs: - 150 - ActiveUS 205953775 Attorney Docket No.
- any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 632 to 648, SEQ ID NO: 829, or SEQ ID NOs: 27927 to 29616.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R249S protein mutation comprises one or more of the SEQ ID NOs: 649 to 665 and SEQ ID NO: 830.
- any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 649 to 665 or SEQ ID NO: 830.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R249S protein mutation comprises one or more of the SEQ ID NOs: 649 to 665, SEQ ID NO: 830, and SEQ ID NOs: 29617 to 31034.
- any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 649 to 665, SEQ ID NO: 830, or SEQ ID NOs: 29617 to 31034.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R249S protein mutation comprises two or more of the SEQ ID NOs: 649 to 665 and SEQ ID NO: 830.
- any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 649 to 665 or SEQ ID NO: 830.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R249S protein mutation comprises two or more of the SEQ ID NOs: 649 to 665, SEQ ID NO: 830, and SEQ ID NOs: 29617 to 31034.
- any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 649 to 665, SEQ ID NO: 830, or SEQ ID NOs: 29617 to 31034.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R273L protein mutation comprises one or more of the SEQ ID NOs: 666 to 680 and SEQ ID NO: 831.
- any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 666 to 680 or SEQ ID NO: 831.
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- any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 666 to 680, SEQ ID NO: 831, or SEQ ID NOs: 31035 to 31564.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R273L protein mutation comprises two or more of the SEQ ID NOs: 666 to 680 and SEQ ID NO: 831.
- any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 666 to 680 or SEQ ID NO: 831.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R273L protein mutation comprises two or more of the SEQ ID NOs: 666 to 680, SEQ ID NO: 831, and SEQ ID NOs: 31035 to 31564.
- any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 666 to 680, SEQ ID NO: 831, or SEQ ID NOs: 31035 to 31564.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R280K protein mutation comprises one or more of the SEQ ID NO: 681.
- any one of the peptides in the TP53 R280K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 681.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R280K protein mutation comprises one or more of the SEQ ID NO: 681 and SEQ ID NOs: 31565 to 31615.
- any one of the peptides in the TP53 R280K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 681 or SEQ ID NOs: 31565 to 31615.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R280K protein mutation comprises two or more of the SEQ ID NO: 681.
- any one of the peptides in the TP53 R280K composition comprise - 152 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 681.
- the amino acid sequence for a MHC class I peptide composition for the TP53 R280K protein mutation comprises two or more of the SEQ ID NO: 681 and SEQ ID NOs: 31565 to 31615.
- any one of the peptides in the TP53 R280K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 681 or SEQ ID NOs: 31565 to 31615.
- the amino acid sequence for a MHC class I peptide composition for the TP53 S127Y protein mutation comprises one or more of the SEQ ID NOs: 682 to 700 and SEQ ID NO: 832.
- any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 682 to 700 or SEQ ID NO: 832.
- the amino acid sequence for a MHC class I peptide composition for the TP53 S127Y protein mutation comprises one or more of the SEQ ID NOs: 682 to 700, SEQ ID NO: 832, and SEQ ID NOs: 31616 to 32944.
- any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 682 to 700, SEQ ID NO: 832, or SEQ ID NOs: 31616 to 32944.
- the amino acid sequence for a MHC class I peptide composition for the TP53 S127Y protein mutation comprises two or more of the SEQ ID NOs: 682 to 700 and SEQ ID NO: 832.
- any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 682 to 700 or SEQ ID NO: 832.
- the amino acid sequence for a MHC class I peptide composition for the TP53 S127Y protein mutation comprises two or more of the SEQ ID NOs: 682 to 700, SEQ ID NO: 832, and SEQ ID NOs: 31616 to 32944.
- any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 682 to 700, SEQ ID NO: 832, or SEQ ID NOs: 31616 to 32944.
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- the amino acid sequence for a MHC class I peptide composition for the TP53 S241F protein mutation comprises one or more of the SEQ ID NOs: 701 to 718.
- any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 701 to 718.
- the amino acid sequence for a MHC class I peptide composition for the TP53 S241F protein mutation comprises one or more of the SEQ ID NOs: 701 to 718 and SEQ ID NOs: 32945 to 33558.
- any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 701 to 718 or SEQ ID NOs: 32945 to 33558.
- the amino acid sequence for a MHC class I peptide composition for the TP53 S241F protein mutation comprises two or more of the SEQ ID NOs: 701 to 718.
- any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 701 to 718.
- the amino acid sequence for a MHC class I peptide composition for the TP53 S241F protein mutation comprises two or more of the SEQ ID NOs: 701 to 718 and SEQ ID NOs: 32945 to 33558.
- any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 701 to 718 or SEQ ID NOs: 32945 to 33558.
- the amino acid sequence for a MHC class I peptide composition for the TP53 V157F protein mutation comprises one or more of the SEQ ID NOs: 719 to 738.
- any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 719 to 738.
- the amino acid sequence for a MHC class I peptide composition for the TP53 V157F protein mutation comprises one or more of the SEQ ID NOs: 719 to 738 and SEQ ID NOs: 33559 to 34612.
- any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, - 154 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for a MHC class I peptide composition for the TP53 V157F protein mutation comprises two or more of the SEQ ID NOs: 719 to 738.
- any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 719 to 738.
- the amino acid sequence for a MHC class I peptide composition for the TP53 V157F protein mutation comprises two or more of the SEQ ID NOs: 719 to 738 and SEQ ID NOs: 33559 to 34612.
- any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 719 to 738 or SEQ ID NOs: 33559 to 34612.
- the amino acid sequence for a MHC class I peptide composition for the TP53 V272M protein mutation comprises one or more of the SEQ ID NOs: 739 to 755.
- any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 739 to 755.
- the amino acid sequence for a MHC class I peptide composition for the TP53 V272M protein mutation comprises one or more of the SEQ ID NOs: 739 to 755 and SEQ ID NOs: 34613 to 35107.
- any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 739 to 755 or SEQ ID NOs: 34613 to 35107.
- the amino acid sequence for a MHC class I peptide composition for the TP53 V272M protein mutation comprises two or more of the SEQ ID NOs: 739 to 755.
- any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 739 to 755.
- the amino acid sequence for a MHC class I peptide composition for the TP53 V272M protein mutation comprises two or more of the SEQ ID NOs: - 155 - ActiveUS 205953775 Attorney Docket No.
- any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 739 to 755 or SEQ ID NOs: 34613 to 35107.
- the amino acid sequence for a MHC class I peptide composition for the TP53 Y163C protein mutation comprises one or more of the SEQ ID NOs: 756 to 772 and SEQ ID NO: 833.
- any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 756 to 772 or SEQ ID NO: 833.
- the amino acid sequence for a MHC class I peptide composition for the TP53 Y163C protein mutation comprises one or more of the SEQ ID NOs: 756 to 772, SEQ ID NO: 833, and SEQ ID NOs: 35108 to 36047.
- any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 756 to 772, SEQ ID NO: 833, or SEQ ID NOs: 35108 to 36047.
- the amino acid sequence for a MHC class I peptide composition for the TP53 Y163C protein mutation comprises two or more of the SEQ ID NOs: 756 to 772 and SEQ ID NO: 833.
- any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 756 to 772 or SEQ ID NO: 833.
- the amino acid sequence for a MHC class I peptide composition for the TP53 Y163C protein mutation comprises two or more of the SEQ ID NOs: 756 to 772, SEQ ID NO: 833, and SEQ ID NOs: 35108 to 36047.
- any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 756 to 772, SEQ ID NO: 833, or SEQ ID NOs: 35108 to 36047.
- the amino acid sequence for a MHC class I peptide composition for the TP53 Y205C protein mutation comprises one or more of the SEQ ID NOs: 773 to 783.
- any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 773 to 783.
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- the amino acid sequence for a MHC class I peptide composition for the TP53 Y205C protein mutation comprises one or more of the SEQ ID NOs: 773 to 783 and SEQ ID NOs: 36048 to 36596.
- any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 773 to 783 or SEQ ID NOs: 36048 to 36596.
- the amino acid sequence for a MHC class I peptide composition for the TP53 Y205C protein mutation comprises two or more of the SEQ ID NOs: 773 to 783.
- any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 773 to 783.
- the amino acid sequence for a MHC class I peptide composition for the TP53 Y205C protein mutation comprises two or more of the SEQ ID NOs: 773 to 783 and SEQ ID NOs: 36048 to 36596.
- any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 773 to 783 or SEQ ID NOs: 36048 to 36596.
- the amino acid sequence for a MHC class I peptide composition for the TP53 Y234C protein mutation comprises one or more of the SEQ ID NOs: 784 to 794 and SEQ ID NO: 834.
- any one of the peptides in the TP53 Y234C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 784 to 794 or SEQ ID NO: 834.
- the amino acid sequence for a MHC class I peptide composition for the TP53 Y234C protein mutation comprises one or more of the SEQ ID NOs: 784 to 794, SEQ ID NO: 834, and SEQ ID NOs: 36597 to 36796.
- any one of the peptides in the TP53 Y234C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 784 to 794, SEQ ID NO: 834, or SEQ ID NOs: 36597 to 36796.
- the amino acid sequence for a MHC class I peptide composition for the TP53 Y234C protein mutation comprises two or more of the SEQ ID NOs: 784 to 794 and SEQ ID NO: 834.
- any one of the peptides in the TP53 - 157 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 Y234C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 784 to 794 or SEQ ID NO: 834.
- the amino acid sequence for a MHC class I peptide composition for the TP53 Y234C protein mutation comprises two or more of the SEQ ID NOs: 784 to 794, SEQ ID NO: 834, and SEQ ID NOs: 36597 to 36796.
- any one of the peptides in the TP53 Y234C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 784 to 794, SEQ ID NO: 834, or SEQ ID NOs: 36597 to 36796.
- Table 1 shows MHC class I peptide sequences described herein including the respective SEQ ID NO, amino acid sequence corresponding to the SEQ ID NO, protein target (with specific mutation), the seed amino acid sequence (i.e., the amino acid sequence of the wild-type protein fragment), the amino acid substitution (if any) for heteroclitic peptides at positions 2 and C (carboxyl terminus), and notes detailing embodiments in which the peptide may be included in a combined peptide composition as described herein.
- any combination of peptides listed in Table 1 (SEQ ID NOs: 1 to 834) may be used to create a combined peptide composition having between about 2 and about 40 peptides.
- any one of the peptides (peptides 1 to 834; SEQ ID NOs: 1 to 834) in the combined composition comprises an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to any of SEQ ID NOs: 1 to 834.
- Additional amino acid sequences of MHC class I composition peptides are provided in Sequence Listings (SEQ ID NOs: 1280 to 36796).
- any combination of MHC class I peptides disclosed herein may be used to create a combined peptide composition having between about 2 and about 40 peptides.
- any one of the peptides (SEQ ID NOs: 1 to 834 and SEQ ID NOs: 1280 to 36796) in the combined composition comprises or contains an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to any of SEQ ID NOs: 1 to 834 or SEQ ID NOs: 1280 to 36796.
- the composition comprising the MHC class I peptides disclosed herein is an immunogenic composition.
- the composition is a vaccine.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 1, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2901, A2902, A2911, A3002, A3004, A3009, A3010, B1501, B1502, B1503, B1521, B15220, B1525, B1531, C0214, C0302, C0702, C0705, C1202, C1601, C1602, and C16112.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 2, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1501, B1502, B1503, B1512, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, C0202, C0210, C0229, C0302, C0705, C1202, C1203, C1601, C1604, and C16112.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 3, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2901, A2902, A2911, A3002, A3004, A3009, A3010, A3601, B1501, B1502, B1503, B1508, B1511, B1512, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, B4601, C0202, C0210, C0214, C0229, C0302, C0702, C0705, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 4, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3104, A3402, A3601, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 5, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3104, A3401, A3402, A3601, A6602, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 6, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1501, B1502, B1503, B1517, B1521, B15220, B1525, B1527, B1531, B1532, C0202, C0210, C0229, C0302, C1202, C1504, C1509, C1601, C1602, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 7, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2902, A2911, A3002, A3004, A3009, A3010, B1501, B1502, B1503, B1517, B1521, B15220, B1525, B1527, B1531, B1532, C0202, C0210, C0229, C0302, C1202, C1504, C1509, C1601, C1602, and C16112.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 8, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0211, A0214, A02264, A0230, and B1302.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 9, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0211, A0214, A02264, A0230, and B1302.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 10, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 11, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 160 - ActiveUS 205953775 Attorney Docket No.
- HLA alleles present in the subject is selected from the group consisting of A2901, A2902, A2911, A3002, A3004, A3009, A3010, A3601, B1501, B1502, B1503, B1508, B1511, B1512, B1517, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, B3501, B3505, B3508, B3532, B3541, B4601, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0702, C0705, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 12, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1503, B1518, B15220, B1525, B2702, B2704, B2705, B2706, B2707, C0701, C0702, C0704, C0705, C0706, and C0718.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 13, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B1518, B1521, B15220, B1525, C0214, C0702, and C0705.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 14, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1516, B1517, B1524, B5703, B5802, C0202, C0210, C0229, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 15, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, A0206, A0211, A0214, A02264, and B1302.
- the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 16, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 161 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1517, and B1525.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 17, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, and C1202.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 18, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, and C1202.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 19, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 20, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 21, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 22, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 162 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 23, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 24, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 25, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 26, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 27, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402, B1503, B15220, and C1202.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 28, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 163 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3802.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 29, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 30, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 31, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 32, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 33, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 34, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 164 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 35, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 36, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 37, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0205, B1301, B1503, and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 38, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 39, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1503, B15220, B3801, and B3802.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 40, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 165 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1503, and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 41, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1503, and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 42, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 43, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 44, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 45, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 46, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 166 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 47, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4006 and B4101.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 48, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3801 and B3802.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 49, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3801 and B3802.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 50, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0205, B1301, B1302, B1303, B1503, B15220, B3801, B3802, and B5201.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 51, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0207, A0211, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 52, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 167 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0207, A0211, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 53, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 54, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 55, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 56, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 57, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 58, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 168 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 59, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 60, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 61, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 62, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 63, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4101.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 64, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 169 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0207, A0211, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 65, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0207, A0211, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 66, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0207, A0211, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 67, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0207, A0211, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 68, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 69, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 70, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 170 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 71, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 72, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 73, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 74, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 75, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 76, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 171 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 77, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 78, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4006, B4101, and B5001.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 79, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4006, B4101, and B5001.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 80, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0206, A0211, A0214, A0230, and B1302.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 81, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0206, A0211, A0214, A0230, and B1302.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 82, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 172 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 83, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 84, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0204, A0207, A0211, A0230, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 85, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0204, A0207, A0211, A0230, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 86, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0204, A0207, A0211, A0230, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 87, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 88, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 173 - ActiveUS 205953775 Attorney Docket No.
- HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 89, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 90, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 91, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 92, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 93, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 174 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 94, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 95, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 96, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 97, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 98, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924.
- - 175 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 99, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 100, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 101, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4101.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 102, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 103, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, C0102, C0144, C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 104, wherein a peptide with this - 176 - ActiveUS 205953775 Attorney Docket No.
- 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, C0102, C0144, C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 105, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, C0102, C0144, C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 106, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1503, B1510, B1518, B15220, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 107, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B1518, and B15220.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 108, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B1518, and B15220. - 177 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 109, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2403 and A2410.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 110, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 111, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 112, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 113, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C0801, C0803, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 114, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 178 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of B1401, B1402, B1503, B1510, B1518, B15220, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 115, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1503, B1510, B1518, B15220, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 116, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4101.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 117, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 118, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0207, A0211, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 119, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0204, A0205, A0206, A0207, A0211, A0214, A0230, C0501, and C0509.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 120, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 179 - ActiveUS 205953775 Attorney Docket No.
- HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3104, A3402, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 121, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, and C1602.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 122, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 123, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2603, A2630, A3004, A3009, A3401, A3402, A6601, A6602, A6603, A6801, A7404, C0303, C1202, C1504, C1509, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 124, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A2603, A2630, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 125, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A2603, A2630, A3004, A3009, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, C1202, C1504, C1509, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 126, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A2603, A2630, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1504, C1509, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 127, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A2603, A2630, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 128, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, and C1602.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 129, wherein a peptide with this - 181 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5501, B5502, and B5601.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 130, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5501, B5502, and B5601.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 131, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3401, A6601, A6602, A6603, A7404, C0303, C1202, C1504, C1509, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 132, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2603, A2630, A3004, A3009, A3401, A6601, A6602, A6603, A7404, C0303, C1202, C1504, C1509, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 133, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A2603, A2630, A3001, A3004, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1504, C1509, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 134, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 182 - ActiveUS 205953775 Attorney Docket No.
- HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, and C1602.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 135, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0202, C0210, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 136, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0229, C0303, C1202, C1504, C1509, C1601, C1602, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 137, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3002, A3004, A3009, A3010, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0229, C0303, C1202, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 138, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 183 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 139, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3104, A3401, A3402, A3601, A6601, A6602, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, C0303, and C1602.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 140, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 141, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604,
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 142, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3002, A3004, A3009, A3010, A3101, - 184 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 143, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112,
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 144, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604,
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 145, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, A3002, A3004, A3009, A3010, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A7404, A7410, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 146, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3002, A3004, A3009, A3101, A3104, - 185 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 147, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3401, A3402, A6601, A6602, A6603, A7404, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 148, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3401, A3402, A6601, A6602, A6603, A7404, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 149, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3002, A3004, A3009, A3010, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 150, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0303, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 151, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3101, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0202, C0210, C0229, C0303, C1202,
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 152, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3009, A3101, A3104, A3401, A3402, A3601, A6602, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, and C0303.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 153, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0202, C0210, C0229, C0303, C1202, C1504, C1509, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 154, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3101, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0202, C0210, C0229, C0303, C1202, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 155, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A3001, A3004, A3009, A3101, A3104, A3401, A3402, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, C0303, and C1602.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 156, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, and A02264.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 157, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, and A02264.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 158, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, and A02264.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 159, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 160, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 188 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 161, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1504, C1509, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 162, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, A3402, A3601, A7404, C0202, C0210, C0229, C1202, C1504, C1509, C1601, C1602, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 163, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, and A02264.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 164, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1525, C0202, C0210, C0229, C0302, and C1202.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 165, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 189 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A0204, A0205, B1301, B1302, B1303, B1502, B1525, B2705, B4701, B5201, C0704, and C0705.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 166, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B5703, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 167, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 168, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3104, A3402, A3601, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, and C0303.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 169, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 170, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924.
- - 190 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 171, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, C0303, C1202, C1601, C1602, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 172, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3401, A3402, A3601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0303, C1202, and C1602.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 173, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 174, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 175, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3303, A3401, A3402, - 191 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 176, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 177, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5201, C0102, C0144, C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C0704, C0801, C0803, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 178, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, A3402, A3601, A7404, C1202, C1504, C1509, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 179, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202 and A0205.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 180, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 192 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1525, B2705, B4701, B5201, C0704, and C0705.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 181, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 182, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, A3601, A6601, A6602, A6603, A7404, C0303, C1202, C1504, C1509, C1601, C1602, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 183, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924.
- the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 184, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 185, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411.
- - 193 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 186, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3402, A3601, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 187, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601 and C0303.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 188, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601 and C0303.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 189, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, A7404, and C0303.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 190, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5502 and B5601.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 191, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5502 and B5601. - 194 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 192, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5703 and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 193, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5703 and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 194, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 195, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, C0303, and C1602.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 196, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, C0303, and C1602.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 197, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, A7404, C0303, and C1602. - 195 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 198, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5601.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 199, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 200, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 201, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5703, B5802, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 202, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5703, B5802, and C1602.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 203, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, C0102, C0103, C0144, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0702, C0704, C0705, C0801, C0803, - 196 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 204, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0202, C0210, C0214, C0229, C0302, C0602, C0702, C0705, C1202, C1203, C1402, C1403, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 205, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0102, C0144, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0702, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C17
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 206, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0102, C0144, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0702, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C17
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 207, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0602, C0702, C0705, C1202, C1203, C1502, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 208, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2601 and A3401.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 209, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6802 and A6827.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 210, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2601 and A3401.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 211, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A2901, A2902, A2911, A3002, A3009, A3010, A3601, B1502, B1521, B1525, B1531, B3508, B5704, C0202, C0210, C0214, C0229, C0302, C0403, C0501, C0509, C0705, C0801, C0802, C0803, C1202, C1504, C1509, C1601, C1602, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 212, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A2901, A2902, A2911, A3002, A3004, A3009, A3010, A3601, A7404, A7410, B1502, B1521, B1525, B1531, B3508, B5704, C0202, C0210, C0214, C0229, C0302, C0403, C0501, C0509, C0801, C0802, C0803, C1202, C1504, C1509, C1601, C1602, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 213, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0102, C0103, C0144, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0702, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C150
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 214, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0102, C0103, C0144, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0702, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C17
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 215, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0202, C0210, C0214, C0229, C0302, C0602, C0702, C0705, C1202, C1203, C1402, C1403, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 216, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, C0214, C0602, C0702, C0704, C0705, C1402, and C1403.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 217, wherein a peptide with this - 199 - ActiveUS 205953775 Attorney Docket No.
- 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, C0102, C0144, C0214, C0302, C0602, C0702, C0704, C0705, C1202, C1203, C1402, C1403, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 218, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0207, A3601, B1502, B1525, B1531, C0202, C0210, C0214, C0229, C0401, C0403, C0407, C0501, C0509, C0705, C0801, C0802, C0803, C1402, C1403, C1504, C1509, C1601, C1602, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 219, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0109, A0207, A3601, B1502, B1525, B1531, C0202, C0210, C0214, C0229, C0302, C0401, C0403, C0407, C0501, C0509, C0705, C0801, C0802, C0803, C1202, C1402, C1403, C1504, C1509, C1601, C1602, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 220, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A0207, A2901, A2902, A2911, A3002, A3004, A3009, A3010, A3601, A7404, A7410, A8001, B1501, B1502, B1512, B1521, B1525, B1527, B1531, B1532, B3508, B4701, B5704, C0202, C0210, C0214, C0229, C0302, C0401, C0403, C0407, C0501, C0509, C0705, C0801, C0802, C0803,
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 221, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 200 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A2901, A2902, A2911, B1502, B1521, B1525, B1531, B1801, B1802, B3701, B4402, B4404, B4427, B4701, and C1202.
- the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 222, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2901, A2902, A2911, A3601, B1502, B1521, B1525, B1531, and C1202.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 223, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4402, B4403, B4404, B4407, and B4427.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 224, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0211, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 225, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0211, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 226, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B3503, B4201, B4202, B5501, B5502, B5601, B5604, B5610, B6701, B8101, and B8103.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 227, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 201 - ActiveUS 205953775 Attorney Docket No.
- HLA alleles present in the subject is selected from the group consisting of A0202, A0211, B0702, B0705, B3503, B3910, B4201, B4202, B5501, B5502, B5601, B5604, B5610, B6701, B8101, and B8103.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 228, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5703, and B5801.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 229, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5703, and B5801.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 230, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5703, and B5801.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 231, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0211, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 232, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1801, B1802, B1803, B3701, B4402, B4403, B4404, B4407, and B4427.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 233, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 202 - ActiveUS 205953775 Attorney Docket No.
- HLA alleles present in the subject is selected from the group consisting of B1525, C0202, C0210, C0214, C0217, C0229, C0302, C0705, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 234, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1516, B5701, B5702, B5703, B5704, B5801, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 235, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1802, B3701, B4002, B40114, B4102, B4402, B4403, B4404, B4405, B4407, B4427, and B4901.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 236, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4002, B40114, B4102, B4402, B4403, B4404, B4405, B4407, B4427, and B4901.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 237, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B3701, B4002, and B4102.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 238, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5701, B5703, B5704, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 239, wherein a peptide with this - 203 - ActiveUS 205953775 Attorney Docket No.
- 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0211, A02264, B0702, B0705, B4201, B5501, B5502, B5601, B5604, B5610, and B6701.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 240, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, and B1302.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 241, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A7404, B1302, and B1303.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 242, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A7404, B1302, B1303, and B5201.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 243, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, B1301, B1302, B1303, and B5201.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 244, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 204 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, and B1302.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 245, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, A0211, and A02264.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 246, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, A0211, and A02264.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 247, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, A0211, and A02264.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 248, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3501, B3508, and B3541.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 249, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1302, B3701, B4002, B4006, B40114, B4016, B4101, B4102, B4901, B5201, and C0704.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 250, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 205 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1302, B3701, B4002, B4006, B40114, B4016, B4101, B4102, B4901, B5201, and C0704.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 251, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1302, B3701, B4002, B4006, B4102, B4901, B5201, and C0704.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 252, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B3503, B4201, B5108, B5501, B5502, B5601, B5604, B5610, and B6701.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 253, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3910, B4201, B4202, B5108, B5109, B5301, B5501, B5502, B5601, B5604, B5610, and B6701.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 254, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3501, B3503, B3505, B3508, B3532, B3541, B5301, and B5610.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 255, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3501, B3503, B3505, B3508, B3532, B3541, B4201, B5301, B5501, B5502, B5601, B5604, and B5610.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 256, wherein a peptide with this - 206 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 257, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5702, B5703, B5704, B5801, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 258, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1517, B5701, B5702, B5703, B5704, B5801, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 259, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1517, B5701, B5702, B5703, B5704, B5801, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 260, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 261, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 262, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 207 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 263, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 264, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4402, B4403, B4404, B4405, B4407, and B4427.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 265, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 266, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 267, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0303, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 268, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 208 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0303, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 269, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 270, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4101.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 271, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4402, B4403, B4404, B4405, B4407, and B4427.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 272, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2403, A2410, A3004, A3009, A3010, A3201, A7410, B1301, B1516, B1517, B1524, B1525, B5701, B5702, B5703, B5704, B5801, and B5802.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 273, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3201, A3601, A7404, A7405, A7410, B1301, B1501, B1502, B1503, B1516, B1517, B15220, B1524, B1525, B1531, B5701, B5703, B5704, B5802, C0202, C0210, C0214, C0229, C0302, C0705, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 274, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 275, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 276, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3201, A3601, A7410, B1301, B1516, B1517, B1524, B5701, B5702, B5703, B5704, B5801, B5802, C1504, C1509, C1601, C1602, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 277, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 278, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3201, A7410, B1301, B1516, B1517, B1524, B1525, B5701, B5702, B5703, B5704, B5801, B5802, C1504, C1509, C1602, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 279, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 210 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A2403, A2410, A2901, A2902, A2911, A3002, A3004, A3009, A3010, B5701, B5703, and C0705.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 280, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 281, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3002, A3004, A3009, A3010, A3201, A3601, A7410, B1301, B1501, B1502, B1503, B1516, B1517, B15220, B1524, B1525, B1531, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0214, C0229, C0302, C0701, C0705, C0706, C0718, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, and C
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 282, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3004, A3009, A3201, A7404, B1301, B1502, B1516, B1517, B1525, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0214, C0229, C0302, C0701, C0705, C0706, C0718, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 283, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3201, A3601, A7404, A7405, A7410, B1501, B1502, B1503, B1516, B1517, B15220, B1524, B1525, B1531, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0214, C0229, C0302, C0701, C0705, C0706, C0718, C1202, C1203, C1502, C1504, C1509
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 284, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4002, B4016, B4101, and B4102.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 285, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4002, B4016, B4101, B4102, and C0704.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 286, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3201, A3601, A7404, A7405, A7410, B1301, B1501, B1502, B1503, B1516, B1517, B15220, B1524, B1525, B1531, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0229, C0302, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 287, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2901, A2902, A2911, A3002, A3004, A3009, A3010, A3201, A3601, A7404, A7410, B1301, B1501, B1502, B1503, B1517, B15220, B1524, B1525, B1531, B5703, B5704, B5802, C0202, C0210, C0214, C0229, C0302, C0701, C0705, C0706, C0718, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 288, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3002, A3004, A3009, A3010, B1503, B15220, B1525, C0214, C0701, C0705, C0706, and C0718.
- - 212 - ActiveUS 205953775 Attorney Docket No.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 289, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3002, A3004, A3009, A3010, A3201, A7404, A7405, B1301, B1516, B1517, B1525, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0214, C0229, C0302, C0705, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, and C1646.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 290, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4402, B4403, B4404, B4407, and B4427.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 291, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A6802, A6827, and A6901.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 292, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A6802, A6827, and A6901.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 293, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 294, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 213 - ActiveUS 205953775 Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 295, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1302, B1303, B1802, B3701, B4001, B4002, B4006, B40114, B4016, B4101, B4102, B4402, B4403, B4404, B4407, B4415, B4427, B4501, B4507, B4701, B4703, B4901, and B5001.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 296, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1502, B1503, B1518, B15220, B1525, B1531, B1801, B1802, B1803, B2706, B3701, B3802, B4001, B4002, B4006, B40114, B4012, B4016, B4101, B4102, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4701, B4703, B4803, B4901, B5001, B5201, C0701, C0702, C0704, C0705, C0706, C0718, and C
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 297, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1503, B15220, B1802, B1803, B3701, B3802, B4001, B4002, B4006, B40114, B4012, B4016, B4101, B4102, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4701, B4703, B4803, B4901, B5001, B5201, and C0704.
- the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 298, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1502, B1503, B1518, B15220, B1525, B1531, B1801, B1802, B1803, B3701, B4001, B4002, B4006, B40114, B4101, B4102, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4701, B4703, B4901, B5001, C0701, C0702, C0705, C0706, C0718, and C1202.
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Abstract
Described herein is a composition comprising one or more polynucleotides encoding at least two amino acid sequences selected from the group consisting of SEQ ID NOs: 17 to 184. Also described herein is a composition comprising one or more polynucleotides encoding at least two amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 222. Also described herein is a composition comprising one or more polynucleotides encoding at least two amino acid sequences selected from the group consisting of SEQ ID NOs: 223 to 386. Also described herein is a composition comprising one or more polynucleotides encoding at least two amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 794.
Description
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 COMPOSITIONS AND METHODS FOR OPTIMIZED PEPTIDE VACCINES [0001] This application claims the benefit of and priority under 35 U.S.C. § 119(e) to US Provisional Serial No.: 63/583,460, filed September 18, 2023, the contents of which is hereby incorporated by reference in its entirety. [0002] This patent disclosure contains material that is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction of the patent document or the patent disclosure as it appears in the U.S. Patent and Trademark Office patent file or records, but otherwise reserves any and all copyright rights. INCORPORATION BY REFERENCE [0003] All patents, patent applications and publications cited herein are hereby incorporated by reference in their entirety. The disclosures of these publications in their entireties are hereby incorporated by reference into this application. Documents incorporated by reference into this text, or any teachings therein, can be used in the practice of the present invention. Documents incorporated by reference into this text are not admitted being prior art. SEQUENCE LISTING [0004] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The XML copy, created on September 9, 2024, is named 2215269_00133WO1_SL.xml and is 68,996,631 bytes in size. TECHNICAL FIELD [0005] The present invention relates generally to compositions, systems, and methods of peptide vaccines. More particularly, the present invention relates to compositions, systems, and methods of designing peptide vaccines to treat or prevent disease optimized based on predicted population immunogenicity. BACKGROUND [0006] The goal of a peptide vaccine is to train the immune system to recognize and expand its capacity to engage cells that display target peptides to improve the immune response to cancerous cells or pathogens. A peptide vaccine can also be administered to someone who is already diseased to increase their immune response to a causal cancer, other diseases, or pathogen. Alternatively, a peptide vaccine can be administered to induce the immune system to - 1 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 have therapeutic tolerance to one or more peptides. There exists a need for compositions, systems, and methods of peptide vaccines based on prediction of the target peptides that will be displayed to protect a host from cancer, other disease, or pathogen infection. SUMMARY OF THE INVENTION [0007] In one aspect, the invention provides for a composition comprising one or more polynucleotides encoding at least two amino acid sequences, wherein the at least two amino acid sequences are selected from the group consisting of SEQ ID NOs: 17 to 176, and SEQ ID NOs: 178 to 184. [0008] In some embodiments, the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides. In some embodiments, an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. In some embodiments, the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. In some embodiments, each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a CTNNB1 protein. In some embodiments, the fragment of the CTNNB1 protein comprises a mutation selected from the group consisting of CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, and CTNNB1 T41I. [0009] In another aspect, the invention provides for a method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the composition is an immunogenic composition. In some embodiments, the at least two amino acid sequences are SEQ ID NOs: 103 and 104. [0010] In another aspect, the invention provides for composition comprising one or more polynucleotides encoding at least two amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 207 and SEQ ID NOs: 209 to 222. In some embodiments, the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least - 2 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 two peptides encoded by the one or more polynucleotides. In some embodiments, an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. In some embodiments, the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. In some embodiments, each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a KRAS protein. In some embodiments, the fragment of the KRAS protein comprises a mutation selected from the group consisting of KRAS A146T, KRAS A146V, and KRAS Q61H. [0011] In another aspect, the invention provides for a method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the composition is an immunogenic composition. In some embodiments, the at least two amino acid sequences are SEQ ID NOs: 203 and 204. [0012] In another aspect, the invention provides for a composition comprising one or more polynucleotides encoding at least two amino acid sequences, wherein the at least two amino acid sequences are selected from the group consisting of SEQ ID NOs: 223 to 240, SEQ ID NOs: 243 to 293, SEQ ID NOs: 295 to 315, SEQ ID NOs: 317 to 329, SEQ ID NOs: 331 to 339, and SEQ ID NOs: 341 to 386. In some embodiments, the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides. In some embodiments, an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. In some embodiments, the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. In some embodiments, each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a PIK3CA protein. In some embodiments, the fragment of the PIK3CA protein comprises a mutation selected from the group consisting of PIK3CA C420R, - 3 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 PIK3CA E453K, PIK3CA E545A, PIK3CA E726K, PIK3CA G118D, PIK3CA H1047L, PIK3CA N345K, PIK3CA Q546K, PIK3CA Q546R, and PIK3CA R108H. [0013] In another aspect, the invention provides for a method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the composition is an immunogenic composition. In some embodiments, the at least two amino acid sequences are SEQ ID NOs: 308 and 309. [0014] In another aspect, the invention provides for a composition comprising one or more polynucleotides encoding at least two amino acid sequences, wherein the at least two amino acid sequences are selected from the group consisting of SEQ ID NOs: 387 to 445, SEQ ID NOs: 447 to 472, SEQ ID NOs: 474 to 480, SEQ ID NOs: 482 to 500, SEQ ID NOs: 502 to 544, SEQ ID NOs: 546 to 550, SEQ ID NOs: 552 to 564, SEQ ID NOs: 566 to 582, SEQ ID NO: 584, SEQ ID NOs: 586 to 605, SEQ ID NOs: 607 to 633, SEQ ID NOs: 638 to 656, SEQ ID NOs: 659 to 664, and SEQ ID NOs: 666 to 794. In some embodiments, the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides. In some embodiments, an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. In some embodiments, the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. In some embodiments, each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a TP53 protein. In some embodiments, the fragment of the TP53 protein comprises a mutation selected from the group consisting of TP53 C176F, TP53 C176Y, TP53 C238Y, TP53 C275Y, TP53 E285K, TP53 G245S, TP53 G245V, TP53 H179Y, TP53 H193R, TP53 I195T, TP53 K132E, TP53 K132N, TP53 P151S, TP53 R213L, TP53 R249M, TP53 R249S, TP53 R273L, TP53 R280K, TP53 S127Y, TP53 S241F, TP53 V157F, TP53 V272M, TP53 Y163C, TP53 Y205C, and TP53 Y234C. [0015] In another aspect, the invention provides for a method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the - 4 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 composition is an immunogenic composition. In some embodiments, the at least two amino acid sequences are SEQ ID NOs: 474 and 475. [0016] In another aspect, the invention provides for nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834. [0017] In some embodiments, the nucleic acid sequences encode two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834. [0018] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834. [0019] In some embodiments, the composition is administered to a subject. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834. In some embodiments, the nucleic acid sequences are contained in a construct for in vivo expression in a subject of at least one peptide encoded by the nucleic acid sequences. In some embodiments, an administration of the nucleic acid sequences causes the at least one peptide encoded by the nucleic acid sequences to be displayed by an HLA class I molecule in the subject. In some embodiments, the administration of the nucleic acid sequences causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated protein selected from the group consisting of BRAF, CTNNB1, KRAS, PIK3CA, and TP53. In some embodiments, the one or more peptides is a modified or unmodified fragment of a protein, wherein the protein comprises a mutation selected from the group consisting of BRAF G466V, CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, CTNNB1 T41I, KRAS A146T, KRAS A146V, KRAS Q61H, PIK3CA C420R, PIK3CA E453K, PIK3CA E545A, PIK3CA E726K, PIK3CA G118D, PIK3CA H1047L, PIK3CA N345K, PIK3CA Q546K, PIK3CA Q546R, PIK3CA R108H, TP53 C176F, TP53 C176Y, TP53 C238Y, TP53 C275Y, TP53 E285K, TP53 G245S, TP53 G245V, TP53 H179Y, TP53 H193R, TP53 I195T, TP53 K132E, TP53 K132N, TP53 P151S, TP53 R213L, TP53 R249M, TP53 R249S, TP53 R273L, TP53 R280K, TP53 S127Y, TP53 S241F, TP53 - 5 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 V157F, TP53 V272M, TP53 Y163C, TP53 Y205C, and TP53 Y234C. In some embodiments, the composition is administered in an effective amount to a subject to prevent cancer. In some embodiments, the composition is administered in an effective amount to a subject to treat cancer. In some embodiments, the cancer is selected from the group consisting of pancreas, colon, rectum, kidney, bronchus, lung, uterus, cervix, bladder, liver, stomach, brain, breast, ovary, thyroid, and skin. In some embodiments, the composition comprises nucleic acid sequences encoding at least three amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834. [0020] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1 to 834. [0021] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1 to 834. [0022] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 16. [0023] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a BRAF protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 16. [0024] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1 to 16. [0025] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1 to 16. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated BRAF protein. [0026] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 17 to 184. [0027] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 protein mutation. In some - 6 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 17 to 184. [0028] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 17 to 184. [0029] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 17 to 184. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated CTNNB1 protein. [0030] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 222. [0031] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 222. [0032] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 185 to 222. [0033] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 185 to 222. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated KRAS protein. [0034] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 223 to 386. [0035] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 223 to 386. [0036] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 223 to 386. - 7 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0037] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 223 to 386. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated PIK3CA protein. [0038] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 794. [0039] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 794. [0040] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 387 to 794. [0041] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 387 to 794. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated TP53 protein. [0042] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 16. [0043] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a BRAF G466V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 16. [0044] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1 to 16. [0045] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1 to 16. In some embodiments, the peptide composition comprises a peptide derived from a BRAF G466V protein mutation. [0046] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 17 to 36. - 8 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0047] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 D32G protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 17 to 36. [0048] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 17 to 36. [0049] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 17 to 36. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 D32G protein mutation. [0050] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 37 to 52. [0051] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 G34E protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 37 to 52. [0052] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 37 to 52. [0053] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 37 to 52. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 G34E protein mutation. [0054] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 53 to 67. [0055] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S33C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 53 to 67. [0056] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 53 to 67. - 9 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0057] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 53 to 67. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S33C protein mutation. [0058] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 68 to 86. [0059] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S33F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 68 to 86. [0060] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 68 to 86. [0061] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 68 to 86. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S33F protein mutation. [0062] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 87 to 102. [0063] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S37C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 87 to 102. [0064] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 87 to 102. [0065] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 87 to 102. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S37C protein mutation. [0066] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 103 to 119. - 10 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0067] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S37F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 103 to 119. [0068] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 103 to 119. [0069] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 103 to 119. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S37F protein mutation. [0070] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 120 to 134. [0071] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S45F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 120 to 134. [0072] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 120 to 134. [0073] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 120 to 134. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S45F protein mutation. [0074] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 135 to 150. [0075] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S45P protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 135 to 150. [0076] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 135 to 150. - 11 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0077] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 135 to 150. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S45P protein mutation. [0078] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 151 to 167. [0079] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 T41A protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 151 to 167. [0080] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 151 to 167. [0081] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 151 to 167. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 T41A protein mutation. [0082] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 168 to 184. [0083] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 T41I protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 168 to 184. [0084] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 168 to 184. [0085] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 168 to 184. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 T41I protein mutation. [0086] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 193. - 12 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0087] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS A146T protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 193. [0088] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 185 to 193. [0089] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 185 to 193. In some embodiments, the peptide composition comprises a peptide derived from a KRAS A146T protein mutation. [0090] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 194 to 202. [0091] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS A146V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 194 to 202. [0092] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 194 to 202. [0093] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 194 to 202. In some embodiments, the peptide composition comprises a peptide derived from a KRAS A146V protein mutation. [0094] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 203 to 222. [0095] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS Q61H protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 203 to 222. [0096] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 203 to 222. - 13 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0097] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 203 to 222. In some embodiments, the peptide composition comprises a peptide derived from a KRAS Q61H protein mutation. [0098] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 223 to 239. [0099] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA C420R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 223 to 239. [0100] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 223 to 239. [0101] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 223 to 239. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA C420R protein mutation. [0102] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 240 to 255. [0103] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E453K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 240 to 255. [0104] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 240 to 255. [0105] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 240 to 255. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E453K protein mutation. [0106] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 256 to 271. - 14 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0107] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E545A protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 256 to 271. [0108] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 256 to 271. [0109] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 256 to 271. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E545A protein mutation. [0110] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 272 to 290. [0111] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E726K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 272 to 290. [0112] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 272 to 290. [0113] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 272 to 290. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E726K protein mutation. [0114] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 291 to 307. [0115] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA G118D protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 291 to 307. [0116] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 291 to 307. - 15 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0117] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 291 to 307. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA G118D protein mutation. [0118] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 308 to 325. [0119] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA H1047L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 308 to 325. [0120] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 308 to 325. [0121] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 308 to 325. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA H1047L protein mutation. [0122] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 326 to 339. [0123] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA N345K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 326 to 339. [0124] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 326 to 339. [0125] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 326 to 339. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA N345K protein mutation. [0126] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 340 to 358. - 16 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0127] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA Q546K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 340 to 358. [0128] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 340 to 358. [0129] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 340 to 358. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA Q546K protein mutation. [0130] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 359 to 376. [0131] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA Q546R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 359 to 376. [0132] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 359 to 376. [0133] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 359 to 376. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA Q546R protein mutation. [0134] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 377 to 386. [0135] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA R108H protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 377 to 386. [0136] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 377 to 386. - 17 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0137] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 377 to 386. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA R108H protein mutation. [0138] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 403. [0139] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C176F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 403. [0140] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 387 to 403. [0141] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 387 to 403. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C176F protein mutation. [0142] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 404 to 420. [0143] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C176Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 404 to 420. [0144] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 404 to 420. [0145] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 404 to 420. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C176Y protein mutation. [0146] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 421 to 440. - 18 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0147] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C238Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 421 to 440. [0148] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 421 to 440. [0149] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 421 to 440. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C238Y protein mutation. [0150] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 441 to 457. [0151] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C275Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 441 to 457. [0152] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 441 to 457. [0153] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 441 to 457. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C275Y protein mutation. [0154] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 458 to 473. [0155] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 E285K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 458 to 473. [0156] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 458 to 473. - 19 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0157] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 458 to 473. In some embodiments, the peptide composition comprises a peptide derived from a TP53 E285K protein mutation. [0158] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 474 to 492. [0159] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 G245S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 474 to 492. [0160] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 474 to 492. [0161] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 474 to 492. In some embodiments, the peptide composition comprises a peptide derived from a TP53 G245S protein mutation. [0162] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 493 to 511. [0163] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 G245V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 493 to 511. [0164] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 493 to 511. [0165] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 493 to 511. In some embodiments, the peptide composition comprises a peptide derived from a TP53 G245V protein mutation. [0166] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 512 to 529. - 20 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0167] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 H179Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 512 to 529. [0168] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 512 to 529. [0169] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 512 to 529. In some embodiments, the peptide composition comprises a peptide derived from a TP53 H179Y protein mutation. [0170] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 530 to 546. [0171] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 H193R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 530 to 546. [0172] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 530 to 546. [0173] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 530 to 546. In some embodiments, the peptide composition comprises a peptide derived from a TP53 H193R protein mutation. [0174] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 547 to 563. [0175] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 I195T protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 547 to 563. [0176] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 547 to 563. - 21 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0177] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 547 to 563. In some embodiments, the peptide composition comprises a peptide derived from a TP53 I195T protein mutation. [0178] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 564 to 582. [0179] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 K132E protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 564 to 582. [0180] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 564 to 582. [0181] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 564 to 582. In some embodiments, the peptide composition comprises a peptide derived from a TP53 K132E protein mutation. [0182] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 583 to 599. [0183] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 K132N protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 583 to 599. [0184] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 583 to 599. [0185] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 583 to 599. In some embodiments, the peptide composition comprises a peptide derived from a TP53 K132N protein mutation. [0186] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 600 to 614. - 22 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0187] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 P151S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 600 to 614. [0188] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 600 to 614. [0189] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 600 to 614. In some embodiments, the peptide composition comprises a peptide derived from a TP53 P151S protein mutation. [0190] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 615 to 631. [0191] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R213L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 615 to 631. [0192] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 615 to 631. [0193] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 615 to 631. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R213L protein mutation. [0194] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 632 to 648. [0195] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R249M protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 632 to 648. [0196] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 632 to 648. - 23 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0197] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 632 to 648. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R249M protein mutation. [0198] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 649 to 665. [0199] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R249S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 649 to 665. [0200] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 649 to 665. [0201] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 649 to 665. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R249S protein mutation. [0202] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 666 to 680. [0203] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R273L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 666 to 680. [0204] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 666 to 680. [0205] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 666 to 680. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R273L protein mutation. [0206] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NO: 681. - 24 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0207] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R280K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NO: 681. [0208] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NO: 681. [0209] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NO: 681. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R280K protein mutation. [0210] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 682 to 700. [0211] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 S127Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 682 to 700. [0212] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 682 to 700. [0213] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 682 to 700. In some embodiments, the peptide composition comprises a peptide derived from a TP53 S127Y protein mutation. [0214] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 701 to 718. [0215] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 S241F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 701 to 718. [0216] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 701 to 718. - 25 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0217] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 701 to 718. In some embodiments, the peptide composition comprises a peptide derived from a TP53 S241F protein mutation. [0218] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 719 to 738. [0219] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 V157F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 719 to 738. [0220] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 719 to 738. [0221] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 719 to 738. In some embodiments, the peptide composition comprises a peptide derived from a TP53 V157F protein mutation. [0222] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 739 to 755. [0223] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 V272M protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 739 to 755. [0224] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 739 to 755. [0225] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 739 to 755. In some embodiments, the peptide composition comprises a peptide derived from a TP53 V272M protein mutation. [0226] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 756 to 772. - 26 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0227] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 Y163C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 756 to 772. [0228] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 756 to 772. [0229] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 756 to 772. In some embodiments, the peptide composition comprises a peptide derived from a TP53 Y163C protein mutation. [0230] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 773 to 783. [0231] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 Y205C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 773 to 783. [0232] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 773 to 783. [0233] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 773 to 783. In some embodiments, the peptide composition comprises a peptide derived from a TP53 Y205C protein mutation. [0234] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 784 to 794. [0235] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 Y234C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 784 to 794. [0236] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 784 to 794. - 27 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0237] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 784 to 794. In some embodiments, the peptide composition comprises a peptide derived from a TP53 Y234C protein mutation. [0238] In one aspect, the invention provides for nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279. [0239] In some embodiments, the nucleic acid sequences encode two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279. [0240] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279. [0241] In some embodiments, the composition is administered to a subject. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279. In some embodiments, the nucleic acid sequences are contained in a construct for in vivo expression in a subject of at least one peptide encoded by the nucleic acid sequences. In some embodiments, an administration of the nucleic acid sequences causes the at least one peptide encoded by the nucleic acid sequences to be displayed by an HLA class II molecule in the subject. In some embodiments, the administration of the nucleic acid sequences causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class II alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class II alleles, wherein the first plurality of HLA class II alleles and the second plurality of HLA class II alleles differ by at least one HLA class II allele. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated protein selected from the group consisting of BRAF, CTNNB1, KRAS, PIK3CA, and TP53. In some embodiments, the one or more peptides is a modified or unmodified fragment of a protein, wherein the protein comprises a mutation selected from the group consisting of BRAF G466V, CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, CTNNB1 T41I, KRAS A146T, KRAS A146V, KRAS Q61H, PIK3CA C420R, PIK3CA E453K, PIK3CA E545A, PIK3CA E726K, PIK3CA G118D, PIK3CA H1047L, PIK3CA N345K, PIK3CA Q546K, PIK3CA Q546R, PIK3CA R108H, TP53 C176F, TP53 C176Y, TP53 C238Y, TP53 C275Y, TP53 G245S, TP53 G245V, TP53 H179Y, TP53 H193R, TP53 I195T, TP53 K132E, TP53 K132N, TP53 P151S, TP53 R213L, TP53 R249M, - 28 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 TP53 R249S, TP53 R273L, TP53 S127Y, TP53 S241F, TP53 V157F, TP53 V272M, TP53 Y163C, and TP53 Y205C. In some embodiments, the composition is administered in an effective amount to a subject to prevent cancer. In some embodiments, the composition is administered in an effective amount to a subject to treat cancer. In some embodiments, the cancer is selected from the group consisting of pancreas, colon, rectum, kidney, bronchus, lung, uterus, cervix, bladder, liver, stomach, brain, breast, ovary, thyroid, and skin. In some embodiments, the composition comprises nucleic acid sequences encoding at least three amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279. [0242] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 835 to 1279. [0243] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 835 to 1279. [0244] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 844. [0245] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a BRAF protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 844. [0246] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 835 to 844. [0247] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 835 to 844. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated BRAF protein. [0248] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 845 to 935. [0249] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 protein mutation. In some - 29 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 845 to 935. [0250] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 845 to 935. [0251] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 845 to 935. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated CTNNB1 protein. [0252] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 936 to 965. [0253] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 936 to 965. [0254] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 936 to 965. [0255] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 936 to 965. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated KRAS protein. [0256] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 966 to 1065. [0257] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 966 to 1065. [0258] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 966 to 1065. - 30 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0259] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 966 to 1065. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated PIK3CA protein. [0260] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1066 to 1279. [0261] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1066 to 1279. [0262] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1066 to 1279. [0263] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1066 to 1279. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated TP53 protein. [0264] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 844. [0265] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a BRAF G466V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 844. [0266] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 835 to 844. [0267] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 835 to 844. In some embodiments, the peptide composition comprises a peptide derived from a BRAF G466V protein mutation. [0268] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 845 to 854. - 31 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0269] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 D32G protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 845 to 854. [0270] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 845 to 854. [0271] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 845 to 854. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 D32G protein mutation. [0272] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 855 to 864. [0273] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 G34E protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 855 to 864. [0274] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 855 to 864. [0275] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 855 to 864. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 G34E protein mutation. [0276] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NO: 865. [0277] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S33C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NO: 865. [0278] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NO: 865. - 32 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0279] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NO: 865. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S33C protein mutation. [0280] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 866 to 875. [0281] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S33F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 866 to 875. [0282] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 866 to 875. [0283] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 866 to 875. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S33F protein mutation. [0284] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 876 to 885. [0285] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S37C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 876 to 885. [0286] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 876 to 885. [0287] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 876 to 885. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S37C protein mutation. [0288] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 886 to 895. - 33 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0289] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S37F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 886 to 895. [0290] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 886 to 895. [0291] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 886 to 895. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S37F protein mutation. [0292] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 896 to 905. [0293] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S45F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 896 to 905. [0294] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 896 to 905. [0295] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 896 to 905. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S45F protein mutation. [0296] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 906 to 915. [0297] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S45P protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 906 to 915. [0298] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 906 to 915. - 34 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0299] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 906 to 915. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S45P protein mutation. [0300] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 916 to 925. [0301] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 T41A protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 916 to 925. [0302] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 916 to 925. [0303] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 916 to 925. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 T41A protein mutation. [0304] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 926 to 935. [0305] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 T41I protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 926 to 935. [0306] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 926 to 935. [0307] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 926 to 935. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 T41I protein mutation. [0308] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 936 to 945. - 35 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0309] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS A146T protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 936 to 945. [0310] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 936 to 945. [0311] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 936 to 945. In some embodiments, the peptide composition comprises a peptide derived from a KRAS A146T protein mutation. [0312] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 946 to 955. [0313] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS A146V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 946 to 955. [0314] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 946 to 955. [0315] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 946 to 955. In some embodiments, the peptide composition comprises a peptide derived from a KRAS A146V protein mutation. [0316] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 956 to 965. [0317] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS Q61H protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 956 to 965. [0318] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 956 to 965. - 36 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0319] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 956 to 965. In some embodiments, the peptide composition comprises a peptide derived from a KRAS Q61H protein mutation. [0320] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 966 to 975. [0321] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA C420R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 966 to 975. [0322] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 966 to 975. [0323] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 966 to 975. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA C420R protein mutation. [0324] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 976 to 985. [0325] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E453K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 976 to 985. [0326] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 976 to 985. [0327] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 976 to 985. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E453K protein mutation. [0328] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 986 to 995. - 37 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0329] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E545A protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 986 to 995. [0330] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 986 to 995. [0331] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 986 to 995. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E545A protein mutation. [0332] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 996 to 1005. [0333] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E726K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 996 to 1005. [0334] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 996 to 1005. [0335] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 996 to 1005. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E726K protein mutation. [0336] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1006 to 1015. [0337] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA G118D protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1006 to 1015. [0338] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1006 to 1015. - 38 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0339] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1006 to 1015. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA G118D protein mutation. [0340] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1016 to 1025. [0341] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA H1047L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1016 to 1025. [0342] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1016 to 1025. [0343] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1016 to 1025. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA H1047L protein mutation. [0344] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1026 to 1035. [0345] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA N345K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1026 to 1035. [0346] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1026 to 1035. [0347] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1026 to 1035. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA N345K protein mutation. [0348] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1036 to 1045. - 39 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0349] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA Q546K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1036 to 1045. [0350] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1036 to 1045. [0351] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1036 to 1045. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA Q546K protein mutation. [0352] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1046 to 1055. [0353] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA Q546R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1046 to 1055. [0354] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1046 to 1055. [0355] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1046 to 1055. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA Q546R protein mutation. [0356] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1056 to 1065. [0357] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA R108H protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1056 to 1065. [0358] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1056 to 1065. - 40 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0359] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1056 to 1065. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA R108H protein mutation. [0360] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1066 to 1075. [0361] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C176F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1066 to 1075. [0362] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1066 to 1075. [0363] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1066 to 1075. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C176F protein mutation. [0364] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1076 to 1085. [0365] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C176Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1076 to 1085. [0366] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1076 to 1085. [0367] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1076 to 1085. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C176Y protein mutation. [0368] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1086 to 1095. - 41 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0369] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C238Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1086 to 1095. [0370] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1086 to 1095. [0371] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1086 to 1095. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C238Y protein mutation. [0372] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1096 to 1105. [0373] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C275Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1096 to 1105. [0374] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1096 to 1105. [0375] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1096 to 1105. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C275Y protein mutation. [0376] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1106 to 1115. [0377] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 G245S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1106 to 1115. [0378] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1106 to 1115. - 42 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0379] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1106 to 1115. In some embodiments, the peptide composition comprises a peptide derived from a TP53 G245S protein mutation. [0380] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1116 to 1125. [0381] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 G245V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1116 to 1125. [0382] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1116 to 1125. [0383] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1116 to 1125. In some embodiments, the peptide composition comprises a peptide derived from a TP53 G245V protein mutation. [0384] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1126 to 1135. [0385] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 H179Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1126 to 1135. [0386] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1126 to 1135. [0387] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1126 to 1135. In some embodiments, the peptide composition comprises a peptide derived from a TP53 H179Y protein mutation. [0388] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1136 to 1145. - 43 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0389] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 H193R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1136 to 1145. [0390] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1136 to 1145. [0391] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1136 to 1145. In some embodiments, the peptide composition comprises a peptide derived from a TP53 H193R protein mutation. [0392] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1146 to 1155. [0393] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 I195T protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1146 to 1155. [0394] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1146 to 1155. [0395] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1146 to 1155. In some embodiments, the peptide composition comprises a peptide derived from a TP53 I195T protein mutation. [0396] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1156 to 1165. [0397] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 K132E protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1156 to 1165. [0398] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1156 to 1165. - 44 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0399] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1156 to 1165. In some embodiments, the peptide composition comprises a peptide derived from a TP53 K132E protein mutation. [0400] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1166 to 1175. [0401] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 K132N protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1166 to 1175. [0402] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1166 to 1175. [0403] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1166 to 1175. In some embodiments, the peptide composition comprises a peptide derived from a TP53 K132N protein mutation. [0404] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1176 to 1185. [0405] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 P151S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1176 to 1185. [0406] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1176 to 1185. [0407] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1176 to 1185. In some embodiments, the peptide composition comprises a peptide derived from a TP53 P151S protein mutation. [0408] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1186 to 1195. - 45 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0409] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R213L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1186 to 1195. [0410] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1186 to 1195. [0411] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1186 to 1195. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R213L protein mutation. [0412] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1196 to 1205. [0413] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R249M protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1196 to 1205. [0414] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1196 to 1205. [0415] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1196 to 1205. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R249M protein mutation. [0416] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1206 to 1215. [0417] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R249S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1206 to 1215. [0418] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1206 to 1215. - 46 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0419] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1206 to 1215. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R249S protein mutation. [0420] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1216 to 1225. [0421] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R273L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1216 to 1225. [0422] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1216 to 1225. [0423] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1216 to 1225. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R273L protein mutation. [0424] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1226 to 1235. [0425] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 S127Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1226 to 1235. [0426] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1226 to 1235. [0427] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1226 to 1235. In some embodiments, the peptide composition comprises a peptide derived from a TP53 S127Y protein mutation. [0428] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1236 to 1245. - 47 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0429] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 S241F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1236 to 1245. [0430] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1236 to 1245. [0431] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1236 to 1245. In some embodiments, the peptide composition comprises a peptide derived from a TP53 S241F protein mutation. [0432] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1246 to 1255. [0433] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 V157F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1246 to 1255. [0434] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1246 to 1255. [0435] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1246 to 1255. In some embodiments, the peptide composition comprises a peptide derived from a TP53 V157F protein mutation. [0436] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1256 to 1259. [0437] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 V272M protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1256 to 1259. [0438] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1256 to 1259. - 48 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0439] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1256 to 1259. In some embodiments, the peptide composition comprises a peptide derived from a TP53 V272M protein mutation. [0440] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1260 to 1269. [0441] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 Y163C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1260 to 1269. [0442] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1260 to 1269. [0443] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1260 to 1269. In some embodiments, the peptide composition comprises a peptide derived from a TP53 Y163C protein mutation. [0444] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1270 to 1279. [0445] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 Y205C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1270 to 1279. [0446] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1270 to 1279. [0447] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1270 to 1279. In some embodiments, the peptide composition comprises a peptide derived from a TP53 Y205C protein mutation. [0448] In some embodiments, the compositions, including peptide compositions, of the invention are immunogenic compositions. To this end, the invention provides for a method of - 49 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 inducing an immunogenic response in a subject comprising administering to the subject a composition of the invention. [0449] In some embodiments, compositions, including peptide compositions, of the invention are vaccines. [0450] In one aspect, a composition (e.g., a vaccine) comprises nucleic acid sequences encoding for one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834 and SEQ ID NOs: 1280 to 36796, wherein the one or more amino acid sequences encodes for one of more peptides, wherein the one or more peptides is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A0301, A0302, A0305, A1101, A1102, A2301, A2402, A2403, A2407, A2410, A2464, A2501, A2601, A2603, A2608, A2612, A2630, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3101, A3104, A3201, A3301, A3303, A3305, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A6802, A6827, A6901, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, A8001, B0702, B0705, B0801, B1301, B1302, B1303, B1401, B1402, B1403, B1501, B1502, B1503, B1508, B1510, B1511, B1512, B1516, B1517, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, B1537, B1801, B1802, B1803, B2702, B2703, B2704, B2705, B2706, B2707, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3701, B3801, B3802, B3901, B3905, B3906, B3909, B3910, B3924, B4001, B4002, B4006, B4008, B40114, B4012, B4016, B4101, B4102, B4201, B4202, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4601, B4701, B4703, B4801, B4803, B4901, B5001, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B5701, B5702, B5703, B5704, B5801, B5802, B6701, B7301, B7801, B8101, B8103, B8201, B8202, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, and C1803. [0451] In one aspect, a method is described comprising administering to a subject a composition (e.g., a vaccine) in an effective amount to induce an immune response in the - 50 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 subject, the composition comprising nucleic acid sequences encoding for one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834 and SEQ ID NOs: 1280 to 36796. [0452] In some embodiments, the method comprises administering the composition to the subject based on a determination that the subject expresses one or more HLA alleles. In some embodiments, the one or more HLA alleles is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A0301, A0302, A0305, A1101, A1102, A2301, A2402, A2403, A2407, A2410, A2464, A2501, A2601, A2603, A2608, A2612, A2630, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3101, A3104, A3201, A3301, A3303, A3305, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A6802, A6827, A6901, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, A8001, B0702, B0705, B0801, B1301, B1302, B1303, B1401, B1402, B1403, B1501, B1502, B1503, B1508, B1510, B1511, B1512, B1516, B1517, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, B1537, B1801, B1802, B1803, B2702, B2703, B2704, B2705, B2706, B2707, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3701, B3801, B3802, B3901, B3905, B3906, B3909, B3910, B3924, B4001, B4002, B4006, B4008, B40114, B4012, B4016, B4101, B4102, B4201, B4202, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4601, B4701, B4703, B4801, B4803, B4901, B5001, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B5701, B5702, B5703, B5704, B5801, B5802, B6701, B7301, B7801, B8101, B8103, B8201, B8202, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, and C1803. [0453] In one aspect, a method is described for formulating a composition (e.g., a vaccine), the method comprising determining that a subject in need thereof of the composition expresses one or more HLA alleles, and formulating the composition by selecting nucleic acid sequences encoding for one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834 and SEQ ID NOs: 1280 to 36796. - 51 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0454] In some embodiments, the one or more HLA alleles is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A0301, A0302, A0305, A1101, A1102, A2301, A2402, A2403, A2407, A2410, A2464, A2501, A2601, A2603, A2608, A2612, A2630, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3101, A3104, A3201, A3301, A3303, A3305, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A6802, A6827, A6901, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, A8001, B0702, B0705, B0801, B1301, B1302, B1303, B1401, B1402, B1403, B1501, B1502, B1503, B1508, B1510, B1511, B1512, B1516, B1517, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, B1537, B1801, B1802, B1803, B2702, B2703, B2704, B2705, B2706, B2707, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3701, B3801, B3802, B3901, B3905, B3906, B3909, B3910, B3924, B4001, B4002, B4006, B4008, B40114, B4012, B4016, B4101, B4102, B4201, B4202, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4601, B4701, B4703, B4801, B4803, B4901, B5001, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B5701, B5702, B5703, B5704, B5801, B5802, B6701, B7301, B7801, B8101, B8103, B8201, B8202, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, and C1803. [0455] In another aspect, an MHC class II peptide vaccine comprises nucleic acid sequences encoding for one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279 and SEQ ID NOs: 36797 to 61281, wherein the one or more amino acid sequences encodes for one of more peptides, wherein the one or more peptides is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10301, DPA10103- DPB10401, DPA10103-DPB10402, DPA10103-DPB10501, DPA10103-DPB10601, DPA10103-DPB11001, DPA10103-DPB110501, DPA10103-DPB11101, DPA10103- DPB112401, DPA10103-DPB112601, DPA10103-DPB11301, DPA10103-DPB113101, DPA10103-DPB113301, DPA10103-DPB11401, DPA10103-DPB11501, DPA10103- DPB11601, DPA10103-DPB11701, DPA10103-DPB11801, DPA10103-DPB11901, - 52 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPA10103-DPB12001, DPA10103-DPB12101, DPA10103-DPB12301, DPA10103- DPB12901, DPA10103-DPB13001, DPA10103-DPB13101, DPA10103-DPB13401, DPA10103-DPB13901, DPA10103-DPB14001, DPA10103-DPB14101, DPA10103- DPB14801, DPA10103-DPB14901, DPA10103-DPB15001, DPA10103-DPB15101, DPA10103-DPB15501, DPA10103-DPB15901, DPA10103-DPB18001, DPA10104- DPB10101, DPA10104-DPB10301, DPA10104-DPB11001, DPA10104-DPB11301, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105-DPB10301, DPA10105- DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106-DPB10101, DPA10106-DPB11101, DPA10201-DPB10101, DPA10201-DPB10201, DPA10201- DPB10202, DPA10201-DPB10301, DPA10201-DPB10401, DPA10201-DPB10501, DPA10201-DPB10601, DPA10201-DPB110601, DPA10201-DPB11101, DPA10201- DPB11301, DPA10201-DPB113301, DPA10201-DPB11401, DPA10201-DPB11501, DPA10201-DPB11601, DPA10201-DPB11801, DPA10201-DPB11901, DPA10201- DPB13401, DPA10201-DPB14501, DPA10201-DPB15501, DPA10201-DPB19101, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202- DPB10301, DPA10202-DPB10401, DPA10202-DPB10402, DPA10202-DPB10501, DPA10202-DPB10901, DPA10202-DPB110001, DPA10202-DPB110501, DPA10202- DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202-DPB113101, DPA10202-DPB11401, DPA10202-DPB11701, DPA10202-DPB11801, DPA10202- DPB11901, DPA10202-DPB12101, DPA10202-DPB12901, DPA10202-DPB13001, DPA10202-DPB13101, DPA10202-DPB13801, DPA10202-DPB14501, DPA10202- DPB15501, DPA10202-DPB16501, DPA10202-DPB18501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10301, DPA10301- DPB10401, DPA10301-DPB10402, DPA10301-DPB10901, DPA10301-DPB110501, DPA10301-DPB110601, DPA10301-DPB11101, DPA10301-DPB11301, DPA10301- DPB11701, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301- DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10301, DPA10401- DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, DPA10401-DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, DPA10401-DPB14901, DQA10101- DQB10501, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10502, DQA10102-DQB10503, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102- - 53 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQB10604, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103-DQB10501, DQA10103-DQB10503, DQA10103-DQB10601, DQA10103-DQB10602, DQA10103- DQB10609, DQA10104-DQB10501, DQA10105-DQB10501, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301- DQB10302, DQA10301-DQB10303, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302-DQB10302, DQA10302-DQB10303, DQA10302-DQB10304, DQA10303- DQB10301, DQA10303-DQB10302, DQA10303-DQB10303, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10201, DQA10501- DQB10203, DQA10501-DQB10301, DQA10501-DQB10319, DQA10501-DQB10501, DQA10503-DQB10301, DQA10505-DQB10201, DQA10505-DQB10202, DQA10505- DQB10301, DQA10505-DQB10302, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10505-DQB10501, DQA10506-DQB10303, DQA10508- DQB10301, DQA10509-DQB10301, DQA10601-DQB10301, DRB1_0101, DRB1_0102, DRB1_0103, DRB1_0301, DRB1_0401, DRB1_0402, DRB1_0404, DRB1_0405, DRB1_0407, DRB1_0408, DRB1_0410, DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1201, DRB1_1202, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, and DRB1_1602. [0456] In one aspect, a method is described comprising administering to a subject a composition (e.g., a vaccine) in an effective amount to induce an immune response in the subject, the composition comprising nucleic acid sequences encoding for one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279 and SEQ ID NOs: 36797 to 61281. [0457] In some embodiments, the method comprises administering the composition to the subject based on a determination that the subject expresses one or more HLA alleles. In some embodiments, the one or more HLA alleles is selected from the group consisting of DPA10103- DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10301, DPA10103-DPB10401, DPA10103-DPB10402, DPA10103-DPB10501, DPA10103- DPB10601, DPA10103-DPB11001, DPA10103-DPB110501, DPA10103-DPB11101, DPA10103-DPB112401, DPA10103-DPB112601, DPA10103-DPB11301, DPA10103- - 54 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPB113101, DPA10103-DPB113301, DPA10103-DPB11401, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103-DPB11701, DPA10103-DPB11801, DPA10103- DPB11901, DPA10103-DPB12001, DPA10103-DPB12101, DPA10103-DPB12301, DPA10103-DPB12901, DPA10103-DPB13001, DPA10103-DPB13101, DPA10103- DPB13401, DPA10103-DPB13901, DPA10103-DPB14001, DPA10103-DPB14101, DPA10103-DPB14801, DPA10103-DPB14901, DPA10103-DPB15001, DPA10103- DPB15101, DPA10103-DPB15501, DPA10103-DPB15901, DPA10103-DPB18001, DPA10104-DPB10101, DPA10104-DPB10301, DPA10104-DPB11001, DPA10104- DPB11301, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105-DPB10301, DPA10105-DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106- DPB10101, DPA10106-DPB11101, DPA10201-DPB10101, DPA10201-DPB10201, DPA10201-DPB10202, DPA10201-DPB10301, DPA10201-DPB10401, DPA10201- DPB10501, DPA10201-DPB10601, DPA10201-DPB110601, DPA10201-DPB11101, DPA10201-DPB11301, DPA10201-DPB113301, DPA10201-DPB11401, DPA10201- DPB11501, DPA10201-DPB11601, DPA10201-DPB11801, DPA10201-DPB11901, DPA10201-DPB13401, DPA10201-DPB14501, DPA10201-DPB15501, DPA10201- DPB19101, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202-DPB10301, DPA10202-DPB10401, DPA10202-DPB10402, DPA10202- DPB10501, DPA10202-DPB10901, DPA10202-DPB110001, DPA10202-DPB110501, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202- DPB113101, DPA10202-DPB11401, DPA10202-DPB11701, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202-DPB12101, DPA10202-DPB12901, DPA10202- DPB13001, DPA10202-DPB13101, DPA10202-DPB13801, DPA10202-DPB14501, DPA10202-DPB15501, DPA10202-DPB16501, DPA10202-DPB18501, DPA10301- DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10301, DPA10301-DPB10401, DPA10301-DPB10402, DPA10301-DPB10901, DPA10301- DPB110501, DPA10301-DPB110601, DPA10301-DPB11101, DPA10301-DPB11301, DPA10301-DPB11701, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301- DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301-DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401- DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10301, DPA10401-DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, DPA10401- DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, DPA10401-DPB14901, - 55 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQA10101-DQB10501, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102- DQB10502, DQA10102-DQB10503, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10604, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103- DQB10501, DQA10103-DQB10503, DQA10103-DQB10601, DQA10103-DQB10602, DQA10103-DQB10609, DQA10104-DQB10501, DQA10105-DQB10501, DQA10201- DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301-DQB10302, DQA10301-DQB10303, DQA10301-DQB10304, DQA10302- DQB10301, DQA10302-DQB10302, DQA10302-DQB10303, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303-DQB10302, DQA10303-DQB10303, DQA10303- DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10201, DQA10501-DQB10203, DQA10501-DQB10301, DQA10501-DQB10319, DQA10501- DQB10501, DQA10503-DQB10301, DQA10505-DQB10201, DQA10505-DQB10202, DQA10505-DQB10301, DQA10505-DQB10302, DQA10505-DQB10309, DQA10505- DQB10319, DQA10505-DQB10402, DQA10505-DQB10501, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, DQA10601-DQB10301, DRB1_0101, DRB1_0102, DRB1_0103, DRB1_0301, DRB1_0401, DRB1_0402, DRB1_0404, DRB1_0405, DRB1_0407, DRB1_0408, DRB1_0410, DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1201, DRB1_1202, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, and DRB1_1602. [0458] In one aspect, a method is described for formulating a composition (e.g., a vaccine), the method comprising determining that a subject in need thereof of the composition expresses one or more HLA alleles, and formulating the composition by selecting nucleic acid sequences encoding for one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279 and SEQ ID NOs: 36797 to 61281. [0459] In some embodiments, the one or more HLA alleles is selected from the group consisting of DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10301, DPA10103-DPB10401, DPA10103-DPB10402, DPA10103- DPB10501, DPA10103-DPB10601, DPA10103-DPB11001, DPA10103-DPB110501, DPA10103-DPB11101, DPA10103-DPB112401, DPA10103-DPB112601, DPA10103- - 56 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPB11301, DPA10103-DPB113101, DPA10103-DPB113301, DPA10103-DPB11401, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103-DPB11701, DPA10103- DPB11801, DPA10103-DPB11901, DPA10103-DPB12001, DPA10103-DPB12101, DPA10103-DPB12301, DPA10103-DPB12901, DPA10103-DPB13001, DPA10103- DPB13101, DPA10103-DPB13401, DPA10103-DPB13901, DPA10103-DPB14001, DPA10103-DPB14101, DPA10103-DPB14801, DPA10103-DPB14901, DPA10103- DPB15001, DPA10103-DPB15101, DPA10103-DPB15501, DPA10103-DPB15901, DPA10103-DPB18001, DPA10104-DPB10101, DPA10104-DPB10301, DPA10104- DPB11001, DPA10104-DPB11301, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105-DPB10301, DPA10105-DPB10401, DPA10105-DPB11801, DPA10105- DPB15001, DPA10106-DPB10101, DPA10106-DPB11101, DPA10201-DPB10101, DPA10201-DPB10201, DPA10201-DPB10202, DPA10201-DPB10301, DPA10201- DPB10401, DPA10201-DPB10501, DPA10201-DPB10601, DPA10201-DPB110601, DPA10201-DPB11101, DPA10201-DPB11301, DPA10201-DPB113301, DPA10201- DPB11401, DPA10201-DPB11501, DPA10201-DPB11601, DPA10201-DPB11801, DPA10201-DPB11901, DPA10201-DPB13401, DPA10201-DPB14501, DPA10201- DPB15501, DPA10201-DPB19101, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202-DPB10301, DPA10202-DPB10401, DPA10202- DPB10402, DPA10202-DPB10501, DPA10202-DPB10901, DPA10202-DPB110001, DPA10202-DPB110501, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202- DPB11301, DPA10202-DPB113101, DPA10202-DPB11401, DPA10202-DPB11701, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202-DPB12101, DPA10202- DPB12901, DPA10202-DPB13001, DPA10202-DPB13101, DPA10202-DPB13801, DPA10202-DPB14501, DPA10202-DPB15501, DPA10202-DPB16501, DPA10202- DPB18501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10301, DPA10301-DPB10401, DPA10301-DPB10402, DPA10301- DPB10901, DPA10301-DPB110501, DPA10301-DPB110601, DPA10301-DPB11101, DPA10301-DPB11301, DPA10301-DPB11701, DPA10301-DPB11801, DPA10301- DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301-DPB16501, DPA10301-DPB17501, DPA10301- DPB18001, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10301, DPA10401-DPB10402, DPA10401-DPB10501, DPA10401- DPB110501, DPA10401-DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, - 57 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPA10401-DPB14901, DQA10101-DQB10501, DQA10101-DQB10601, DQA10102- DQB10501, DQA10102-DQB10502, DQA10102-DQB10503, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10604, DQA10102-DQB10609, DQA10102- DQB10611, DQA10103-DQB10501, DQA10103-DQB10503, DQA10103-DQB10601, DQA10103-DQB10602, DQA10103-DQB10609, DQA10104-DQB10501, DQA10105- DQB10501, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301-DQB10302, DQA10301-DQB10303, DQA10301- DQB10304, DQA10302-DQB10301, DQA10302-DQB10302, DQA10302-DQB10303, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303-DQB10302, DQA10303- DQB10303, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10201, DQA10501-DQB10203, DQA10501-DQB10301, DQA10501- DQB10319, DQA10501-DQB10501, DQA10503-DQB10301, DQA10505-DQB10201, DQA10505-DQB10202, DQA10505-DQB10301, DQA10505-DQB10302, DQA10505- DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10505-DQB10501, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, DQA10601- DQB10301, DRB1_0101, DRB1_0102, DRB1_0103, DRB1_0301, DRB1_0401, DRB1_0402, DRB1_0404, DRB1_0405, DRB1_0407, DRB1_0408, DRB1_0410, DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1201, DRB1_1202, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, and DRB1_1602. [0460] In another aspect, an MHC class I and/or MHC class II peptide vaccine comprises nucleic acid sequences encoding for one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 61281, wherein the one or more amino acid sequences encodes for one of more peptides, wherein the one or more peptides is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A0301, A0302, A0305, A1101, A1102, A2301, A2402, A2403, A2407, A2410, A2464, A2501, A2601, A2603, A2608, A2612, A2630, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3101, A3104, A3201, A3301, A3303, A3305, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A6802, A6827, A6901, A74, A7401, A7402, A7403, A7404, A7405, A7406, - 58 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 A7407, A7408, A7409, A7410, A7411, A7413, A8001, B0702, B0705, B0801, B1301, B1302, B1303, B1401, B1402, B1403, B1501, B1502, B1503, B1508, B1510, B1511, B1512, B1516, B1517, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, B1537, B1801, B1802, B1803, B2702, B2703, B2704, B2705, B2706, B2707, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3701, B3801, B3802, B3901, B3905, B3906, B3909, B3910, B3924, B4001, B4002, B4006, B4008, B40114, B4012, B4016, B4101, B4102, B4201, B4202, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4601, B4701, B4703, B4801, B4803, B4901, B5001, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B5701, B5702, B5703, B5704, B5801, B5802, B6701, B7301, B7801, B8101, B8103, B8201, B8202, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, C1803, DPA10103-DPB10101, DPA10103-DPB10201, DPA10103- DPB10202, DPA10103-DPB10301, DPA10103-DPB10401, DPA10103-DPB10402, DPA10103-DPB10501, DPA10103-DPB10601, DPA10103-DPB11001, DPA10103- DPB110501, DPA10103-DPB11101, DPA10103-DPB112401, DPA10103-DPB112601, DPA10103-DPB11301, DPA10103-DPB113101, DPA10103-DPB113301, DPA10103- DPB11401, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103-DPB11701, DPA10103-DPB11801, DPA10103-DPB11901, DPA10103-DPB12001, DPA10103- DPB12101, DPA10103-DPB12301, DPA10103-DPB12901, DPA10103-DPB13001, DPA10103-DPB13101, DPA10103-DPB13401, DPA10103-DPB13901, DPA10103- DPB14001, DPA10103-DPB14101, DPA10103-DPB14801, DPA10103-DPB14901, DPA10103-DPB15001, DPA10103-DPB15101, DPA10103-DPB15501, DPA10103- DPB15901, DPA10103-DPB18001, DPA10104-DPB10101, DPA10104-DPB10301, DPA10104-DPB11001, DPA10104-DPB11301, DPA10104-DPB11501, DPA10105- DPB10101, DPA10105-DPB10301, DPA10105-DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106-DPB10101, DPA10106-DPB11101, DPA10201- DPB10101, DPA10201-DPB10201, DPA10201-DPB10202, DPA10201-DPB10301, DPA10201-DPB10401, DPA10201-DPB10501, DPA10201-DPB10601, DPA10201- DPB110601, DPA10201-DPB11101, DPA10201-DPB11301, DPA10201-DPB113301, DPA10201-DPB11401, DPA10201-DPB11501, DPA10201-DPB11601, DPA10201- - 59 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPB11801, DPA10201-DPB11901, DPA10201-DPB13401, DPA10201-DPB14501, DPA10201-DPB15501, DPA10201-DPB19101, DPA10202-DPB10101, DPA10202- DPB10201, DPA10202-DPB10202, DPA10202-DPB10301, DPA10202-DPB10401, DPA10202-DPB10402, DPA10202-DPB10501, DPA10202-DPB10901, DPA10202- DPB110001, DPA10202-DPB110501, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202-DPB113101, DPA10202-DPB11401, DPA10202- DPB11701, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202-DPB12101, DPA10202-DPB12901, DPA10202-DPB13001, DPA10202-DPB13101, DPA10202- DPB13801, DPA10202-DPB14501, DPA10202-DPB15501, DPA10202-DPB16501, DPA10202-DPB18501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB10301, DPA10301-DPB10401, DPA10301-DPB10402, DPA10301-DPB10901, DPA10301-DPB110501, DPA10301-DPB110601, DPA10301- DPB11101, DPA10301-DPB11301, DPA10301-DPB11701, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301- DPB14901, DPA10301-DPB15501, DPA10301-DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401- DPB10202, DPA10401-DPB10301, DPA10401-DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, DPA10401-DPB11301, DPA10401-DPB113301, DPA10401- DPB11401, DPA10401-DPB14901, DQA10101-DQB10501, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10502, DQA10102-DQB10503, DQA10102- DQB10601, DQA10102-DQB10602, DQA10102-DQB10604, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103-DQB10501, DQA10103-DQB10503, DQA10103- DQB10601, DQA10103-DQB10602, DQA10103-DQB10609, DQA10104-DQB10501, DQA10105-DQB10501, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201- DQB10303, DQA10301-DQB10301, DQA10301-DQB10302, DQA10301-DQB10303, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302-DQB10302, DQA10302- DQB10303, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303-DQB10302, DQA10303-DQB10303, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401- DQB10319, DQA10501-DQB10201, DQA10501-DQB10203, DQA10501-DQB10301, DQA10501-DQB10319, DQA10501-DQB10501, DQA10503-DQB10301, DQA10505- DQB10201, DQA10505-DQB10202, DQA10505-DQB10301, DQA10505-DQB10302, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10505- DQB10501, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, - 60 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQA10601-DQB10301, DRB1_0101, DRB1_0102, DRB1_0103, DRB1_0301, DRB1_0401, DRB1_0402, DRB1_0404, DRB1_0405, DRB1_0407, DRB1_0408, DRB1_0410, DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1201, DRB1_1202, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, and DRB1_1602. [0461] In one aspect, a method is described comprising administering to a subject a composition (e.g., a vaccine) in an effective amount to induce an immune response in the subject, the composition comprising nucleic acid sequences encoding for one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 61281. [0462] In some embodiments, the method comprises administering the composition to the subject based on a determination that the subject expresses one or more HLA alleles. In some embodiments, the one or more HLA alleles is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A0301, A0302, A0305, A1101, A1102, A2301, A2402, A2403, A2407, A2410, A2464, A2501, A2601, A2603, A2608, A2612, A2630, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3101, A3104, A3201, A3301, A3303, A3305, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A6802, A6827, A6901, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, A8001, B0702, B0705, B0801, B1301, B1302, B1303, B1401, B1402, B1403, B1501, B1502, B1503, B1508, B1510, B1511, B1512, B1516, B1517, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, B1537, B1801, B1802, B1803, B2702, B2703, B2704, B2705, B2706, B2707, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3701, B3801, B3802, B3901, B3905, B3906, B3909, B3910, B3924, B4001, B4002, B4006, B4008, B40114, B4012, B4016, B4101, B4102, B4201, B4202, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4601, B4701, B4703, B4801, B4803, B4901, B5001, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B5701, B5702, B5703, B5704, B5801, B5802, B6701, B7301, B7801, B8101, B8103, B8201, B8202, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, - 61 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, C1803, DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10301, DPA10103- DPB10401, DPA10103-DPB10402, DPA10103-DPB10501, DPA10103-DPB10601, DPA10103-DPB11001, DPA10103-DPB110501, DPA10103-DPB11101, DPA10103- DPB112401, DPA10103-DPB112601, DPA10103-DPB11301, DPA10103-DPB113101, DPA10103-DPB113301, DPA10103-DPB11401, DPA10103-DPB11501, DPA10103- DPB11601, DPA10103-DPB11701, DPA10103-DPB11801, DPA10103-DPB11901, DPA10103-DPB12001, DPA10103-DPB12101, DPA10103-DPB12301, DPA10103- DPB12901, DPA10103-DPB13001, DPA10103-DPB13101, DPA10103-DPB13401, DPA10103-DPB13901, DPA10103-DPB14001, DPA10103-DPB14101, DPA10103- DPB14801, DPA10103-DPB14901, DPA10103-DPB15001, DPA10103-DPB15101, DPA10103-DPB15501, DPA10103-DPB15901, DPA10103-DPB18001, DPA10104- DPB10101, DPA10104-DPB10301, DPA10104-DPB11001, DPA10104-DPB11301, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105-DPB10301, DPA10105- DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106-DPB10101, DPA10106-DPB11101, DPA10201-DPB10101, DPA10201-DPB10201, DPA10201- DPB10202, DPA10201-DPB10301, DPA10201-DPB10401, DPA10201-DPB10501, DPA10201-DPB10601, DPA10201-DPB110601, DPA10201-DPB11101, DPA10201- DPB11301, DPA10201-DPB113301, DPA10201-DPB11401, DPA10201-DPB11501, DPA10201-DPB11601, DPA10201-DPB11801, DPA10201-DPB11901, DPA10201- DPB13401, DPA10201-DPB14501, DPA10201-DPB15501, DPA10201-DPB19101, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202- DPB10301, DPA10202-DPB10401, DPA10202-DPB10402, DPA10202-DPB10501, DPA10202-DPB10901, DPA10202-DPB110001, DPA10202-DPB110501, DPA10202- DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202-DPB113101, DPA10202-DPB11401, DPA10202-DPB11701, DPA10202-DPB11801, DPA10202- DPB11901, DPA10202-DPB12101, DPA10202-DPB12901, DPA10202-DPB13001, DPA10202-DPB13101, DPA10202-DPB13801, DPA10202-DPB14501, DPA10202- DPB15501, DPA10202-DPB16501, DPA10202-DPB18501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10301, DPA10301- DPB10401, DPA10301-DPB10402, DPA10301-DPB10901, DPA10301-DPB110501, - 62 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPA10301-DPB110601, DPA10301-DPB11101, DPA10301-DPB11301, DPA10301- DPB11701, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301- DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10301, DPA10401- DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, DPA10401-DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, DPA10401-DPB14901, DQA10101- DQB10501, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10502, DQA10102-DQB10503, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102- DQB10604, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103-DQB10501, DQA10103-DQB10503, DQA10103-DQB10601, DQA10103-DQB10602, DQA10103- DQB10609, DQA10104-DQB10501, DQA10105-DQB10501, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301- DQB10302, DQA10301-DQB10303, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302-DQB10302, DQA10302-DQB10303, DQA10302-DQB10304, DQA10303- DQB10301, DQA10303-DQB10302, DQA10303-DQB10303, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10201, DQA10501- DQB10203, DQA10501-DQB10301, DQA10501-DQB10319, DQA10501-DQB10501, DQA10503-DQB10301, DQA10505-DQB10201, DQA10505-DQB10202, DQA10505- DQB10301, DQA10505-DQB10302, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10505-DQB10501, DQA10506-DQB10303, DQA10508- DQB10301, DQA10509-DQB10301, DQA10601-DQB10301, DRB1_0101, DRB1_0102, DRB1_0103, DRB1_0301, DRB1_0401, DRB1_0402, DRB1_0404, DRB1_0405, DRB1_0407, DRB1_0408, DRB1_0410, DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1201, DRB1_1202, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, and DRB1_1602. [0463] In one aspect, a method is described for formulating a composition (e.g., a vaccine), the method comprising determining that a subject in need thereof of the composition expresses one or more HLA alleles, and formulating the composition by selecting nucleic acid sequences - 63 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 encoding for one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 61281. [0464] In some embodiments, the one or more HLA alleles is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A0301, A0302, A0305, A1101, A1102, A2301, A2402, A2403, A2407, A2410, A2464, A2501, A2601, A2603, A2608, A2612, A2630, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3101, A3104, A3201, A3301, A3303, A3305, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A6802, A6827, A6901, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, A8001, B0702, B0705, B0801, B1301, B1302, B1303, B1401, B1402, B1403, B1501, B1502, B1503, B1508, B1510, B1511, B1512, B1516, B1517, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, B1537, B1801, B1802, B1803, B2702, B2703, B2704, B2705, B2706, B2707, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3701, B3801, B3802, B3901, B3905, B3906, B3909, B3910, B3924, B4001, B4002, B4006, B4008, B40114, B4012, B4016, B4101, B4102, B4201, B4202, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4601, B4701, B4703, B4801, B4803, B4901, B5001, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B5701, B5702, B5703, B5704, B5801, B5802, B6701, B7301, B7801, B8101, B8103, B8201, B8202, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, C1803, DPA10103- DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10301, DPA10103-DPB10401, DPA10103-DPB10402, DPA10103-DPB10501, DPA10103- DPB10601, DPA10103-DPB11001, DPA10103-DPB110501, DPA10103-DPB11101, DPA10103-DPB112401, DPA10103-DPB112601, DPA10103-DPB11301, DPA10103- DPB113101, DPA10103-DPB113301, DPA10103-DPB11401, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103-DPB11701, DPA10103-DPB11801, DPA10103- DPB11901, DPA10103-DPB12001, DPA10103-DPB12101, DPA10103-DPB12301, DPA10103-DPB12901, DPA10103-DPB13001, DPA10103-DPB13101, DPA10103- DPB13401, DPA10103-DPB13901, DPA10103-DPB14001, DPA10103-DPB14101, DPA10103-DPB14801, DPA10103-DPB14901, DPA10103-DPB15001, DPA10103- - 64 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPB15101, DPA10103-DPB15501, DPA10103-DPB15901, DPA10103-DPB18001, DPA10104-DPB10101, DPA10104-DPB10301, DPA10104-DPB11001, DPA10104- DPB11301, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105-DPB10301, DPA10105-DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106- DPB10101, DPA10106-DPB11101, DPA10201-DPB10101, DPA10201-DPB10201, DPA10201-DPB10202, DPA10201-DPB10301, DPA10201-DPB10401, DPA10201- DPB10501, DPA10201-DPB10601, DPA10201-DPB110601, DPA10201-DPB11101, DPA10201-DPB11301, DPA10201-DPB113301, DPA10201-DPB11401, DPA10201- DPB11501, DPA10201-DPB11601, DPA10201-DPB11801, DPA10201-DPB11901, DPA10201-DPB13401, DPA10201-DPB14501, DPA10201-DPB15501, DPA10201- DPB19101, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202-DPB10301, DPA10202-DPB10401, DPA10202-DPB10402, DPA10202- DPB10501, DPA10202-DPB10901, DPA10202-DPB110001, DPA10202-DPB110501, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202- DPB113101, DPA10202-DPB11401, DPA10202-DPB11701, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202-DPB12101, DPA10202-DPB12901, DPA10202- DPB13001, DPA10202-DPB13101, DPA10202-DPB13801, DPA10202-DPB14501, DPA10202-DPB15501, DPA10202-DPB16501, DPA10202-DPB18501, DPA10301- DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10301, DPA10301-DPB10401, DPA10301-DPB10402, DPA10301-DPB10901, DPA10301- DPB110501, DPA10301-DPB110601, DPA10301-DPB11101, DPA10301-DPB11301, DPA10301-DPB11701, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301- DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301-DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401- DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10301, DPA10401-DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, DPA10401- DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, DPA10401-DPB14901, DQA10101-DQB10501, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102- DQB10502, DQA10102-DQB10503, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10604, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103- DQB10501, DQA10103-DQB10503, DQA10103-DQB10601, DQA10103-DQB10602, DQA10103-DQB10609, DQA10104-DQB10501, DQA10105-DQB10501, DQA10201- DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10301-DQB10301, - 65 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQA10301-DQB10302, DQA10301-DQB10303, DQA10301-DQB10304, DQA10302- DQB10301, DQA10302-DQB10302, DQA10302-DQB10303, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303-DQB10302, DQA10303-DQB10303, DQA10303- DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10201, DQA10501-DQB10203, DQA10501-DQB10301, DQA10501-DQB10319, DQA10501- DQB10501, DQA10503-DQB10301, DQA10505-DQB10201, DQA10505-DQB10202, DQA10505-DQB10301, DQA10505-DQB10302, DQA10505-DQB10309, DQA10505- DQB10319, DQA10505-DQB10402, DQA10505-DQB10501, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, DQA10601-DQB10301, DRB1_0101, DRB1_0102, DRB1_0103, DRB1_0301, DRB1_0401, DRB1_0402, DRB1_0404, DRB1_0405, DRB1_0407, DRB1_0408, DRB1_0410, DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1201, DRB1_1202, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, and DRB1_1602. BRIEF DESCRIPTION OF THE DRAWINGS [0465] The following figures depict illustrative embodiments of the invention. [0466] FIG.1 is a flow chart of a vaccine optimization method. [0467] FIG.2 is a flow chart of a vaccine optimization method with seed set compression. [0468] FIG.3 shows the predicted population coverage for MHC class I vaccines for single mutations in cancer-related genes. Each row describes the coverage of a vaccine for a single mutation in one of the BRAF, CTNNB1, KRAS, PIK3CA, and TP53 genes. The columns describe the predicted population coverage of each vaccine for a specific gene mutation (e.g., BRAF G466V) at varying number of peptides in the vaccine as annotated at the top of the column. [0469] FIG.4 shows the predicted population coverage for MHC class II vaccines for single mutations in cancer-related genes. Each row describes the coverage of a vaccine for a single mutation in one of the BRAF, CTNNB1, KRAS, PIK3CA, and TP53 genes. The columns describe the predicted population coverage of each vaccine for a specific gene mutation (e.g., BRAF G466V) at varying number of peptides in the vaccine as annotated at the top of the column. - 66 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0470] FIG.5 shows predicated peptide-HLA hits by vaccine size for a KRAS G12V vaccine for the HLA diplotype HLA-A02:03, HLA-A11:01, HLA-B55:02, HLA-B58:01, HLA- C03:02, HLA-C03:03. [0471] FIG.6 is a table showing the respective probabilities of target presentations for various mutated protein targets across different cancers. [0472] FIG.7 is a flow chart showing a multiple target (combined) vaccine optimization method. [0473] FIG.8 shows an example Python implementation of the MERGEMULTI function for combined vaccine design procedures. DETAILED DESCRIPTION [0474] The practice of the embodiments disclosed herein can employ, unless otherwise indicated, conventional techniques of genetics, molecular biology, protein chemistry, computational biology, and formulation science. [0475] All references cited in this disclosure are hereby incorporated by reference in their entireties. In addition, any manufacturers’ instructions or catalogues for any products cited or mentioned herein are incorporated by reference. Documents incorporated by reference into this text, or any teachings therein, can be used in the practice of the present invention. Documents incorporated by reference into this text are not admitted to be prior art. Definitions [0476] The following are definitions of terms used in the present specification. The initial definition provided for a group or term herein applies to that group or term throughout the present specification individually or as part of another group, unless otherwise indicated. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. [0477] The term “a” or “an” means at least one, unless clearly indicated otherwise. The term “about” preceding a numerical value includes ± 10% of the recited value. For example, a concentration of about 1 mg/mL includes 0.9 mg/mL to 1.1 mg/mL. Likewise, a concentration range of about 1% to 10% (w/v) includes 0.9% (w/v) to 11% (w/v). [0478] Furthermore, “and/or” is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term “and/or” as used in a phrase such as “A and/or B” is intended to include A and B, A or B, A (alone), and B (alone). - 67 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 Likewise, the term “and/or” as used in a phrase such as “A, B, and/or C” is intended to include A, B, and C; A, B, or C; A or B; A or C; B or C; A and B; A and C; B and C; A (alone); B (alone); and C (alone). [0479] The term “peptide” means a chain of amino acids of any length, for example, an amino acid polymer. The peptide can be linear or branched, can comprise modified amino acids, and can be interrupted by non-amino acids. Except where indicated otherwise, e.g., for the abbreviations for the uncommon or unnatural amino acids set forth herein, the three-letter and one-letter abbreviations, as used in the art, are used herein to represent amino acid residues. Groups or strings of amino acid abbreviations are used to represent peptides. Except where specifically indicated, peptides are indicated with the N-terminus on the left and the sequence is written from the N-terminus to the C-terminus. [0480] The term “composition” is meant to encompass, and is not limited to, pharmaceutical compositions and nutraceutical compositions, such as a vaccine, containing drug substance (e.g., nucleic acids or peptides). The composition may also contain one or more excipients that are inactive ingredients or compounds devoid of pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of a human. [0481] The terms “immunogenic composition,” and “immunogenic peptide composition,” mean a composition that can induce an immune response (e.g., an adaptive immune response) in a subject, unless clearly indicated otherwise. In some embodiments, the “immunogenic composition” or the “immunogenic peptide composition” is a vaccine composition. In some embodiments, the “immunogenic composition” or the “immunogenic peptide composition” can generate acquired immunity against a pathogen or disease in a subject. In some embodiments, the acquired immunity does not prevent the disease in the subject but reduces its severity. In some embodiments, the “immunogenic composition” or the “immunogenic peptide composition” (e.g., a vaccine) promotes immune system tolerance for one or more proteins. [0482] The term “therapeutically effective amount” or “effective amount” refers to any amount that is necessary or sufficient for achieving or promoting a desired outcome. In some instances, “an effective amount” is a therapeutically effective amount. A “therapeutically effective amount” is any amount that is necessary or sufficient for promoting or achieving a desired biological response in a subject. The “effective amount” for any particular application can vary depending on such factors as the disease or condition being treated or intended to be prevented, the particular agent being administered, the size/weight of the subject, or the severity - 68 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of the disease or condition to be treated or prevented. One of ordinary skill in the art can empirically determine the effective amount of a particular agent without necessitating undue experimentation. [0483] The terms “subject” and “patient” are used interchangeably herein. The terms “subject” and “subjects” refer to an animal, preferably a mammal including a nonprimate and a primate (e.g., a monkey such as a cynomolgus monkey, a chimpanzee, and a human), and a human. The term “animal” also includes, but is not limited to, companion animals such as cats and dogs; zoo animals; wild animals; farm or sport animals such as ruminants, non-ruminants, livestock and fowl (e.g., horses, cattle, sheep, pigs, turkeys, ducks, and chickens); and laboratory animals, such as rodents (e.g., mice, rats), rabbits; and guinea pigs, as well as animals that are cloned or modified, either genetically or otherwise (e.g., transgenic animals). In some embodiments, the term “subject” or “patient” refers to a human. [0484] The terms “treating,” “treatment,” and “therapy” as used herein refer to the attempted reduction or amelioration of the progression, severity and/or duration of a disorder, or the attempted amelioration of one or more symptoms thereof resulting from the administration of one or more modalities (e.g., one or more vaccines or therapeutic agents such as a composition described herein). In some embodiments, a subject is successfully “treated” for a disease or disorder if the patient shows total, partial, or transient alleviation or elimination of at least one symptom or measurable physical parameter associated with the disease or disorder. [0485] As used herein, the terms “prevent,” “preventing,” “prevention,” “alleviate,” or “alleviating” refer to the prevention, inhibition, or lessening of the recurrence, onset, or development of a disorder or a symptom thereof in a subject resulting from the administration of a therapy (e.g., a vaccine), or the administration of a combination of therapies (e.g., a combination of vaccine(s) and/or therapeutic agents). [0486] Units, prefixes, and symbols are denoted in their Système International d’Unités (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range, and any individual value provided herein can serve as an endpoint for a range that includes other individual values provided herein. For example, a set of values such as 1, 2, 3, 8, 9, and 10 is also a disclosure of a range of numbers from 1-10, from 1-8, from 3-9, and so forth. Likewise, a disclosed range is a disclosure of each individual value (i.e., intermediate) encompassed by the range, including integers and fractions. For example, a stated range of 5-10 is also a disclosure of 5, 6, 7, 8, 9, and 10 individually, and of 5.2, 7.5, 8.7, and so forth. - 69 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 Composition/Vaccine Design Considerations [0487] In some embodiments, the disclosure provides for compositions (e.g., vaccines) that incorporate peptide sequences that will be displayed by Major Histocompatibility Complex (MHC) molecules on cells and train the immune system to recognize cancer or pathogen diseased cells. The terms MHC and HLA are used interchangeably herein to denote Major Histocompatibility Complex molecules without restriction to species. In some embodiments, the disclosure provides for compositions (e.g., vaccines) that incorporate peptide sequences that will be displayed by MHC molecules on cells to induce therapeutic tolerance in antigen-specific immunotherapy for autoimmune diseases (Alhadj Ali et al., 2017, Gibson, et al.2015). In some embodiments, a composition (e.g., a vaccine) comprises one or more peptides. In some embodiments, a composition (e.g., a vaccine) includes an RNA (e.g., mRNA) or DNA construct administered for expression in vivo that encodes for one or more peptides. [0488] The immunogenic compositions and methods described herein are applicable for designing and preparing a broad range of compositions including vaccine compositions. [0489] The term peptide-HLA binding is defined to be the binding of a peptide to an HLA allele, and can either be computationally predicted, experimentally observed, or computationally predicted using experimental observations. The metric or score of peptide-HLA binding can be expressed as affinity (for example, based on the equilibrium dissociation constant (KD), measured in molar units (M)), percentile rank, binary at a predetermined threshold, probability, rate of disassociation, or other metrics as are known in the art. The term peptide display or peptide-HLA display describes the binding of a peptide to an HLA allele on the surface of a cell. Peptide binding to an HLA allele is required for peptide display by that HLA allele. The metric or score of peptide-HLA display can be expressed as affinity (for example, based on the equilibrium dissociation constant (KD), measured in molar units (M)), percentile rank, binary at a predetermined threshold, probability, or other metrics as are known in the art. In some embodiments, metrics of peptide-HLA binding are used for metrics of peptide-HLA display since peptide-HLA display depends upon peptide-HLA binding. [0490] The term peptide-HLA immunogenicity metric is defined as the activation of T cells based upon their recognition of a peptide when bound by an HLA allele. The term peptide-HLA immunogenicity score is another term for a peptide-HLA immunogenicity metric, and the terms are interchangeable. A peptide-HLA immunogenicity metric can vary from individual to individual, and the metric for peptide-HLA immunogenicity can be expressed as a probability, a - 70 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 binary indicator, or other metric that relates to the likelihood that a peptide-HLA combination will be immunogenic. In some embodiments, peptide-HLA immunogenicity is defined as the induction of immune tolerance based upon the recognition of a peptide when bound by an HLA allele. A peptide-HLA immunogenicity metric can be computationally predicted, experimentally observed, or computationally predicted using experimental observations. In some embodiments, a peptide-HLA immunogenicity metric is based only upon peptide-HLA binding, since peptide-HLA binding is necessary for peptide-HLA immunogenicity. In some embodiments, peptide-HLA immunogenicity data or computational predictions of peptide-HLA immunogenicity can be included and combined with scores for peptide binding or peptide display in the methods disclosed herein. One way of combining the scores is using immunogenicity data for peptides assayed for immunogenicity in diseased or vaccinated individuals and assigning peptides to the HLA allele that displayed them in the individual by choosing the HLA allele that computational methods predict has the highest likelihood of display. For peptides that are not experimentally assayed, computational predictions of binding can be used. In some embodiments, different computational methods of predicting peptide-HLA immunogenicity or peptide-HLA binding can be combined (Liu et al., 2020b). For a given set of peptides and a set of HLA alleles, the term peptide-HLA hits is the number of unique combinations of peptides and HLA alleles that exhibit peptide-HLA immunogenicity or binding at a predetermined threshold. For example, a peptide-HLA hit of 2 can mean that one peptide is predicted to be bound (or trigger T cell activation) by two different HLA alleles, two peptides are predicted to be bound (or trigger T cell activation) by two different HLA alleles, or two peptides are predicted to be bound (or trigger T cell activation) by the same HLA allele. For a given set of peptides and HLA frequencies, HLA haplotype frequencies, or HLA diplotype frequencies, the expected number of peptide-HLA hits is the average number of peptide-HLA hits in each set of HLAs that represent an individual, weighted by their frequency of occurrence. [0491] Peptide display by an MHC molecule is necessary, but not sufficient, for a peptide to be immunogenic and cause the recognition of the resulting peptide-MHC complex by an individual’s T cells to trigger T cell activation, expansion, and immune memory. In some embodiments, ELISPOT (Slota et al., 2011) or the Multiplex Identification of Antigen-Specific T Cell Receptors Using a Combination of Immune Assays and Immune Receptor Sequencing (MIRA) assay (Klinger et al., 2015) are used to score peptide display or affinity (e.g., a peptide immunogenicity that requires peptide binding) by an MHC molecule (e.g., HLA allele, measured as a peptide-HLA binding score). In some embodiments, experimental data from - 71 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 assays such as the ELISPOT (Slota et al., 2011) or the MIRA assay can be used to produce a peptide-HLA immunogenicity metric with respect to a peptide and an HLA allele in a given experimental context or individual. In some embodiments, experimental data from assays such as the ELISPOT (Slota et al., 2011) or the MIRA assay can be combined with machine learning based predictions for scoring peptide display by an MHC molecule or peptide binding (e.g., binding affinity) by an MHC molecule (e.g., HLA allele, measured as a peptide-HLA binding score) for determining a peptide-HLA immunogenicity metric. In some embodiments, the MHCflurry or NetMHCpan (Reynisson et al., 2020) computational methods are used to predict MHC class I display of a peptide by an HLA allele. In some embodiments, the NetMHCIIpan computational method (Reynisson et al., 2020) is used to predict MHC class II display of a peptide by an HLA allele (see Table 1). [0492] In some embodiments, a composition (e.g., an immunogenic composition) includes nucleic acids sequences encoding for one or more peptides, wherein the one or more peptides is MHC restricted (also referred to as HLA restricted). In some embodiments, a composition (e.g., an immunogenic composition) includes one or more peptides, wherein the one or more peptides is MHC restricted (also referred to as HLA restricted). In some embodiments, an MHC restriction of a peptide sequence refers to the presence of an MHC (or HLA) allele in a subject that allows for peptide-HLA display, peptide-HLA binding, or peptide-HLA immunogenicity for the peptide. An HLA allele is abbreviated by its locus, its two digit allele group, and its two or three digit specific HLA protein. For example, the HLA allele HLA-A*02:01 is abbreviated as A0201. For MHC Class II alleles that begin with DP, DQ, or DR, the first digit is part of the locus, followed by a two or three digit allele group and a two or three digit specific HLA protein. For example, the HLA allele DPA1*01:03 is abbreviated DPA10103 and DRB1*15:01 is abbreviated DRB1_1501. In some embodiments, a composition is designed based on MHC restrictions such that one or more peptides (or nucleic acids encoding for one or more peptides) is included in the composition based on a determination that one or more MHC (or HLA) alleles is present in a subject in need thereof of the composition. In some embodiments, the MHC (or HLA) alleles present in the subject are determined to allow for display or immunogenicity (peptide-HLA display or peptide-HLA immunogenicity) of the one or more peptides (or nucleic acids encoding for one or more peptides) in the composition. In some embodiments, the HLA alleles present or expressed in a subject are used to select one or more peptides (or nucleic acids encoding the peptides) for inclusion in a composition to be administered to the subject. In some embodiments, the selection is based on the likelihood that a given HLA allele expressed in the - 72 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 subject is capable of binding to a given peptide (or nucleic acid encoding the peptide) in the composition. In some embodiments, a composition is designed based on MHC restrictions such that one or more peptides (or nucleic acids encoding for one or more peptides) is included in the composition based on a determination of the MHC (or HLA) alleles present in a desired population of people. Population based HLA allele frequencies can be determined from the Allele Frequency Net Database, the HLA haplotype frequencies provided in Liu et al., Cell Systems 11, Issue 2, p.131-146 (Liu et al., 2020a), or other sources known in the art. In some embodiments, algorithms such as OptiVax are used for peptide selection using population HLA frequencies (Liu et al., 2020a, Liu et al., 2022). A given peptide sequence can have more than one MHC restriction. For example, SEQ ID NO: 16 has an MHC restriction that includes an HLA allele selected from the group consisting of A3201, B1517, and B1525. In some embodiments, a peptide (or nucleic acid sequences encoding for the peptide) is included in a composition only if two or more MHC (or HLA) alleles are present the subject that are also in the MHC restriction of the peptide. For example, the peptide (or nucleic acid sequences encoding for the peptide) containing SEQ ID NO: 16 is included in the composition only if a subject has both A3201 and B1517 alleles. In some embodiments, MHC restrictions can be based on both MHC class I and MHC class II alleles. [0493] In some embodiments, the one or more amino acid sequences is selected for inclusion in a composition (e.g., a vaccine) based on an MHC restriction that includes an HLA allele described in the notes field of the respective SEQ ID NO entry in the sequence listing. For example, in the sequence listing, SEQ ID NO: 16 has a note filed that states: “HLAs: A3201 B1517 B1525.” Thus, in some embodiments, SEQ ID NO:16 is included in the composition if it is determined that an individual in need thereof of the composition expresses one or more of the HLA alleles selected from the group consisting of A3201, B1517, and B1525. Other sequences listed in the sequence listing are considered for inclusion in a composition based on their corresponding HLA alleles as listed in their respective notes field. In some embodiments, the one or more amino acid sequences is selected for inclusion in the MHC class II peptide vaccine based on an MHC restriction that includes an HLA allele described in the notes field of the respective SEQ ID NO entry in the sequence listing. For example, SEQ ID NO: 835 has an MHC restriction that includes an HLA allele selected from the group consisting of DRB1_0101, DRB1_0701, DRB1_0901, DRB1_1001, DPA10103-DPB10601, DPA10103-DPB15001, DPA10105-DPB15001, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401- DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. In some embodiments, the - 73 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 one or more amino acid sequences is selected for inclusion in the MHC class I and/or MHC class II peptide vaccine based on an MHC restriction that includes an HLA allele described in the notes field of the respective SEQ ID NO entry in the sequence listing. [0494] Non-limiting MHC restrictions for entries in the sequence listing are provided in a sequence’s entry free text. In some embodiments, a peptide sequence is preferably selected for inclusion in a composition based on an individual’s HLA type that is included in the sequences’ non-limiting annotated MHC restrictions. For example, SEQ ID NO: 16 has a non-limiting MHC restriction that includes HLA alleles selected from the group consisting of A3201, B1517, and B1525, and thus in some embodiments SEQ ID NO: 16 would be included in peptide candidates for a vaccine for an individual where one or more of these HLA alleles is present. [0495] In some embodiments, computational methods such as MHCflurry (O’Donnell et al., 2018, O’Donnell et al., 2020, incorporated by reference in their entireties herein), NetMHCpan (Reynisson et al., 2020, incorporated by reference in its entirety herein), and NetMHCIIpan (Reynisson et al., 2020) are used to predict either MHC class I (MHCflurry, NetMHCpan) or class II (NetMHCIIpan) display of peptides by an HLA allele. In other embodiments, other methods of determining peptide-HLA binding are used as disclosed in International Publication No. WO 2005/042698, incorporated by reference in its entirety herein. NetMHCpan-4.1 and NetMHCIIpan-4.0 utilize the NNAlign_MA algorithm (Alvarez et al., 2019, incorporated by reference in its entirety herein) for predicting peptide-HLA binding. NNAlign_MA is in turn based upon the NNAlign (Nielsen et al., 2009, Nielsen et al., 2017, incorporated by reference in their entireties herein) neural network. NetMHCpan-4.1 (Reynisson et al., 2020) uses NNAlign_MA networks with at least 180 one-hot encoded inputs that describe the peptide sequence (9 residues x 20 possible amino acids per residue = 180 inputs). Networks with both 56 and 66 hidden neurons and two outputs are utilized (Alvarez et al., 2019). One output produces a binding affinity data type and the other output produces a mass spectrometry based eluted ligand data type (Alvarez et al., 2019). In some embodiments, the binding affinity data type is used as a peptide-HLA binding metric. In some embodiments, the binding affinity data type is used as a peptide-HLA display metric. In some embodiments, the eluted ligand data type output is used as a peptide-HLA binding metric. In some embodiments, the eluted ligand data type output is used as a peptide-HLA display metric. In some embodiments, the binding affinity data type is used as a peptide-HLA immunogenicity metric. In some embodiments, the eluted ligand data type is used as a peptide-HLA immunogenicity metric. Each network architecture - 74 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 (56 or 66 hidden neurons) is trained with 5 different random parameter initializations and 5-fold cross-validation resulting in a total of 50 individual trained networks (2 architectures x 5 initializations x 5 cross-validation). These 50 trained networks are used as an ensemble with 25 networks having at least 10,800 parameters (180 inputs x 56 neurons) and 25 networks consist of at least 11,880 parameters (180 inputs x 66 neurons). Thus, the ensemble of 50 networks in NetMHCpan-4.1 consists of at least 567,000 parameters that must be evaluated with at least 567,000 arithmetic operations for computing peptide-MHC binding. NetMHCIIpan-4.1 (Reynisson et al., 2020) uses NNAlign_MA networks with at least 180 inputs that describe the peptide sequence (9 x 20 = 180 inputs). Networks with 2, 10, 20, 40, and 60 hidden neurons and two outputs are utilized (Alvarez et al., 2019). Each network architecture (2, 10, 20, 40, or 60 hidden neurons) is trained with 10 different random parameter initializations and 5-fold cross- validation resulting in a total of 250 individual trained networks (5 architectures x 10 initializations x 5 cross-validation). These 250 trained networks are used as an ensemble with 50 networks having at least 360 parameters (180 inputs x 2 neurons), 50 networks having at least 1800 parameters (180 inputs x 10 neurons), 50 networks having at least 3600 parameters (180 inputs x 20 neurons), 50 networks having at least 7200 parameters (180 inputs x 40 neurons), and 50 networks having at least 10,800 parameters (180 inputs x 60 neurons). Thus, the ensemble of 250 networks in NetMHCIIpan-4.0 consists of at least 1,188,000 parameters that must be evaluated with at least 1,188,000 arithmetic operations for computing peptide-MHC binding. [0496] In some embodiments, computational methods used to predict either MHC class I (e.g., MHCflurry, NetMHCpan) or class II (e.g., NetMHCIIpan) peptide-HLA binding scores or peptide-HLA immunogenicity metrics are based upon data from experimental mass spectrometry observations of peptides bound by MHC molecules. In some embodiments, computational methods used to predict either MHC class I (e.g., MHCflurry, NetMHCpan) or class II (e.g., NetMHCIIpan) peptide-HLA binding scores or peptide-HLA immunogenicity metrics are based upon data from experimental observations of peptide-MHC binding affinity. In some embodiments, experimental observations of peptide-MHC binding affinity or immunogenicity, including mass spectrometry measurements of peptide-HLA binding and measurements of T cell activation, can be found in databases such as the Immune Epitope Database (IEDB) (Vita et al., 2018). The output of MHCflurry 2.0 (O’Donnell et al., 2020, incorporated by reference in its entirety herein) is based upon 493,473 mass spectrometry measurements of peptide-HLA binding, and 219,596 affinity measurements of peptide-HLA - 75 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 binding. The output of NetMHCpan-4.1 (Reynisson et al., 2020) is based upon 665,492 mass spectrometry measurements of peptide-HLA binding, and 52,402 affinity measurements of peptide-HLA binding. The output of NetMHCIIpan-4.0 (Reynisson et al., 2020) is based upon 381,066 mass spectrometry measurements of peptide-HLA binding, and 44,861 affinity measurements of peptide-HLA binding. [0497] A peptide is displayed by an MHC molecule when it binds within the groove of the MHC molecule and is transported to the cell surface where it can be recognized by a T cell receptor. A target peptide refers to a foreign peptide or a self-peptide. In some embodiments, a peptide that is part of the normal proteome in a healthy individual is a self-peptide, and a peptide that is not part of the normal proteome is a foreign peptide. In some embodiments, target peptides can be part of the normal proteome that exhibit aberrant expression (e.g., cancer-testis antigens such as NY-ESO-1). Foreign peptides can be generated by mutations in normal self- proteins in tumor cells that create epitopes called neoantigens, or by pathogenic infections. In some embodiments, a neoantigen is any subsequence of a human protein, where the subsequence contains one or more altered amino acids or protein modifications that do not appear in a healthy individual. Therefore, in this disclosure, foreign peptide refers to an amino acid sequence encoding a fragment of a target protein/peptide (or a full-length protein/peptide), the target protein/peptide consisting of a neoantigen protein, a pathogen proteome, or any other undesired protein that is non-self and is expected to be bound and displayed by an HLA allele. [0498] Protein genes identified by their UniProt ID that are frequently mutated in cancer include RASK_HUMAN (also called KRAS), AKT1_HUMAN, BRAF_HUMAN, CTNB1_HUMAN (also called CTNNB1), EGFR_HUMAN, GTF2I_HUMAN, RASH_HUMAN (also called HRAS), IDHC_HUMAN (also called IDH1), RASN_HUMAN (also called NRAS), PIK3CA_HUMAN, PTEN_HUMAN, and P53_HUMAN (also called TP53). We describe a missense mutation in a protein by the one letter amino acid code for the wild-type amino acid, the amino acid position of the mutation, and the one letter amino acid code that is present in the mutated protein. For example, KRAS G12D is a mutation in the KRAS protein of position 12 from glycine to aspartic acid (G12D). Proteins may contain multiple mutations at different positions. Herein we may refer to a gene without the “_HUMAN” suffix for conciseness. [0499] KRAS gene mutations are the most frequently mutated oncogenes in cancer, but they have been very difficult to treat with small molecule therapeutics. The KRAS protein is part of - 76 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 a signaling pathway that controls cellular growth and point mutations in the protein can cause constitutive pathway activation and uncontrolled cell growth. Single amino acid KRAS mutations result in minor changes in protein structure, making it difficult to engineer small molecule drugs that recognize a mutant specific binding pocket and inactivate KRAS signaling. KRAS oncogenic mutations include the mutation of position 12 from glycine to aspartic acid (G12D), glycine to valine (G12V), glycine to arginine (G12R), or glycine to cystine (G12C); or the mutation of position 13 from glycine to aspartic acid (G13D). The corresponding foreign peptides contain these mutations. KRAS is a member of the RAS family of genes that also includes HRAS and NRAS. KRAS, HRAS, and NRAS have identical sequences from residue 1 to residue 86. Thus, all of the vaccines and associated peptide sequences described herein for a mutation in one RAS family member can be used for the identical mutation in any other RAS family member (e.g., a KRAS G12D vaccine is also a vaccine for HRAS G12D). [0500] Certain self-proteins, such as cancer-testis antigens, are present in cancerous cells at aberrantly high levels and thus can be targets for vaccination to induce an intolerant T cell response against cells displaying peptides derived from these self-proteins on MHC molecules. Examples of these cancer-related proteins by their UniProt IDs include CTG1B_HUMAN (also known as NY-ESO-1), MAGA1_HUMAN, MAGA3_HUMAN, MAGA4_HUMAN, MAGC1_HUMAN, MAGC3_HUMAN, SSX2_HUMAN, PRAME_HUMAN, KKLC1_HUMAN (also known as CT83), PMEL_HUMAN (as known as gp100), TYRP1_HUMAN (also known as gp75), TYRP2_HUMAN (also known as DCT), and MAR1_HUMAN. [0501] Autoimmune disorders are caused by the loss of self-tolerance by the immune system to self-proteins and are involved in autoimmune disorders such as diabetes, multiple sclerosis, and autoimmune encephalomyelitis. Induction of tolerance for autoimmune-related self- peptides can be accomplished by antigen-specific tolerization using the delivery of vaccine antigens with a tolerization protocol. An example of a protocol for the induction of tolerance with a lipid-nanoparticle (LNP) encapsulating RNA (e.g., mRNA-LNP) vaccine is described by Krienke et al., 2021 and is incorporated by reference in its entirety herein. Examples of autoimmune disease-related proteins include UniProt IDs INS_HUMAN (also known as insulin), and MOG_HUMAN (also known as Myelin-oligodendrocyte glycoprotein). Individuals with diabetes can suffer from a lack of tolerance to INS_HUMAN, and individuals - 77 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 with multiple sclerosis or autoimmune encephalomyelitis can suffer from a lack of tolerance to MOG_HUMAN. [0502] A challenge for the design of peptide vaccines is the diversity of human MHC alleles (HLA alleles) that each have specific preferences for the peptide sequences they will display. The Human Leukocyte Antigen (HLA) loci, located within the MHC, encode the HLA class I and class II molecules. There are three classical class I loci (HLA-A, HLA-B, and HLA-C) and three loci that encode class II molecules (HLA-DR, HLA-DQ, and HLA-DP). An individual’s HLA type describes the alleles they carry at each of these loci. Peptides of length of between about 8 and about 11 residues can bind to HLA class I (or MHC class I) molecules whereas those peptides of length of between about 13 and about 25 residues bind to HLA class II (or MHC class II) molecules (Rist et al., 2013; Chicz et al., 1992). Human populations that originate from different geographies have differing frequencies of HLA alleles, and these populations exhibit linkage disequilibrium between HLA loci that result in population specific haplotype frequencies. In some embodiments, methods are disclosed for creating effective vaccines that include consideration of the HLA allelic frequency in the target population, as well as linkage disequilibrium between HLA genes to achieve a set of peptides that is likely to be robustly displayed. [0503] The present disclosure provides for compositions, systems, and methods of vaccine designs that produce immunity to single or multiple targets. In some embodiments, a target is a neoantigen protein sequence, a pathogen proteome, or any other undesired protein sequence that is non-self and is expected to be bound and displayed by an HLA molecule (also referred to herein as an HLA allele). When a target is present in an individual, it may result in multiple peptide sequences that are displayed by a variety of HLA alleles. In some embodiments, it may be desirable to create a vaccine that includes selected self-peptides, and thus these selected self- peptides are considered to be the target peptides for this purpose. [0504] Because immunogenicity may vary from individual to individual, one method to increase the probability of vaccine efficacy is to use a diverse set of target peptides (e.g., at least two peptides) to increase the chances that some subset of them will be immunogenic in a given individual. Prior research using mouse models has shown that most MHC displayed peptides are immunogenic, but immunogenicity varies from individual to individual as described in Croft et al. (2019). In some embodiments, experimental peptide-HLA immunogenicity data are used - 78 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 to determine which target peptides and their modifications will be effective immunogens in a vaccine. [0505] Considerations for the design of peptide vaccines are outlined in Liu et al., Cell Systems 11, Issue 2, p.131-146 (Liu et al., 2020a) and Liu et al., Cell Systems 12, Issue 1, p. 102-107 (Liu et al., 2020b) and U.S. Patent No.11,058,751 and U.S. Patent No.11,161,892, which are incorporated by reference in their entireties herein. [0506] Certain target peptides may not bind with high affinity to a wide range of HLA molecules. To increase the binding of target peptides to HLA molecules, their amino acid composition can be altered to change one or more anchor residues or other residues. In some embodiments, to increase the immunogenicity of a target peptide when displayed by HLA molecules, a target peptide’s amino acid composition can be altered to change one or more residues. Anchor residues are amino acids that interact with an HLA molecule and have the largest influence on the affinity of a peptide for an HLA molecule. Peptides with one or more altered amino acid residues are called heteroclitic peptides. In some embodiments, heteroclitic peptides include target peptides with residue modifications at anchor positions. In some embodiments, heteroclitic peptides include target peptides with residue modifications at non- anchor positions. In some embodiments, heteroclitic peptides include target peptides with residue modifications that include unnatural amino acids and amino acid derivatives. Modifications to create heteroclitic peptides can improve the binding of peptides to both MHC class I and MHC class II molecules, and the modifications required can be both peptide and MHC class specific. Since peptide anchor residues face the MHC molecule groove, they are less visible than other peptide residues to T cell receptors. Thus, heteroclitic peptides with anchor residue modifications have been observed to induce a T cell response where the stimulated T cells also respond to unmodified peptides. It has been observed that the use of heteroclitic peptides in a vaccine can improve a vaccine’s effectiveness (Zirlik et al., 2006). In some embodiments, the immunogenicity of heteroclitic peptides are experimentally determined and their ability to activate T cells that also recognize the corresponding base (also called seed) peptide of the heteroclitic peptide is determined, as is known in the art (Houghton et al., 2007). In some embodiments, these assays of the immunogenicity and cross-reactivity of heteroclitic peptides are performed when the heteroclitic peptides are displayed by specific HLA alleles. - 79 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 Peptide vaccines to induce immunity to one or more targets [0507] In some embodiments, a method is provided for formulating peptide vaccines using a single vaccine design for one or more targets. In some embodiments, a single target is a foreign protein with a specific mutation (e.g., KRAS G12D). In some embodiments, a single target is a self-protein (e.g., a protein that is overexpressed in tumor cells such as cancer/testis antigens). In some embodiments, a single target is a pathogen protein (e.g., a protein contained in a viral proteome). In some embodiments, multiple targets can be used (e.g., both KRAS G12D and KRAS G13D). [0508] In some embodiments, the method includes extracting peptides to construct a candidate set from all target proteome sequences (e.g., entire KRAS G12D protein) as described in Liu et al. (2020a). [0509] FIGs.1 and 2 depict flow charts, for example, vaccine design methods that can be used for MHC class I or MHC class II vaccine design. A Candidate Peptide Set (see FIGs.1 and 2) is comprised of target peptides extracted by windowing an input protein sequence. In some embodiments, extracted target peptides are of amino acid length of between about 8 and about 10 (e.g., for MHC class I binding (Rist et al., 2013)). In some embodiments, the extracted target peptides presented by MHC class I molecules are longer than 10 amino acid residues, such as 11 residues (Trolle et al., 2016). In some embodiments, extracted target peptides are of length between about 13 and about 25 (e.g., for class II binding (Chicz et al., 1992)). In some embodiments, sliding windows of various size ranges described herein are used over the entire proteome. In some embodiments, other target peptide lengths for MHC class I and class II sliding windows can be utilized. In some embodiments, computational predictions of proteasomal cleavage are used to filter or select peptides in the candidate set. One computational method for predicting proteasomal cleavage is described by Nielsen et al. (2005). In some embodiments, peptide mutation rates, glycosylation, cleavage sites, or other criteria can be used to filter peptides as described in Liu et al. (2020a). In some embodiments, peptides can be filtered based upon evolutionary sequence variation above a predetermined threshold. Evolutionary sequence variation can be computed with respect to other species, other pathogens, other pathogen strains, or other related organisms. In some embodiments, a first peptide set is the candidate set. [0510] As shown in FIGs.1-2, in some embodiments, the next step of the method includes scoring the target peptides in the candidate set for peptide-HLA binding to all considered HLA - 80 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 alleles as described in Liu et al. (2020a) and Liu et al. (2020b). In some embodiments, a first peptide set is the candidate set after scoring the target peptides. Scoring can be accomplished for human HLA molecules, mouse H-2 molecules, swine SLA molecules, or MHC molecules of any species for which prediction algorithms are available or can be developed. Thus, vaccines targeted at non-human species can be designed with the method. Scoring metrics can include the affinity for a target peptide to an HLA allele in nanomolar, eluted ligand, presentation, and other scores that can be expressed as percentile rank or any other metric. The candidate set may be further filtered to exclude peptides whose predicted binding cores do not contain a particular pathogenic or neoantigen target residue of interest or whose predicted binding cores contain the target residue in an anchor position. The candidate set may also be filtered for target peptides of specific lengths, such as length 9 for MHC class I, for example. In some embodiments, scoring of target peptides is accomplished with experimental data or a combination of experimental data and computational prediction methods. When computational models are unavailable to make peptide-HLA binding predictions for particular (peptide, HLA) pairs, the binding value for such pairs can be defined by the mean, median, minimum, or maximum immunogenicity value taken over supported pairs, a fixed value (such as an indication of no binding), or inferred using other techniques, including a function of the prediction of the most similar (peptide, HLA) pair available in the scoring model. [0511] In some embodiments, a base set (also referred to as seed set herein) is constructed by selecting peptides from the scored candidate set using individual peptide-HLA binding or immunogenicity criteria (e.g., first peptide set) (FIG.1). In some embodiments, since a given peptide has multiple peptide-HLA scores, the selection can be based on the peptide-HLA binding score or peptide-HLA immunogenicity metric with the best affinity or highest immunogenicity (e.g., predicted to bind the strongest or activate T cells the most for a given HLA allele). The criteria used for scoring peptide-HLA binding during the scoring procedure can accommodate different goals during the base set selection and vaccine design phases. For example, a target peptide with peptide-HLA binding affinities of 500 nM may be displayed by an individual that is diseased, but at a lower frequency than a target peptide with a 50 nM peptide-HLA binding affinity. During the combinatorial design phase of a vaccine, a more constrained affinity criteria may be used (e.g., when selecting a third peptide set, the Vaccine for Target(s) in FIGs.1 and 2), such a 50 nM, to increase the probability that a vaccine peptide will be found and displayed by HLA molecules. In some embodiments, a relatively less constrained threshold (e.g., less than about 1000 nM or less than about 500 nM) of peptide-HLA - 81 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 immunogenicity or peptide-HLA binding is used as a first threshold for filtering candidate peptide-HLA scores (the first Peptide Scoring and Score Filtering step in FIGs.1 and 2) and a relatively more constrained second threshold (e.g., less than about 50 nM) is used for filtering expanded set peptide-HLA scores (the second Peptide Filtering and Scoring step in FIGs.1 and 2) for their scores for specific HLA alleles. In some embodiments, specific peptide-HLA scores are not used for modified peptides for a given HLA for vaccine design when their unmodified counterpart peptide does not pass the first less constrained threshold. Filtering of peptide-HLA scores can occur for any relevant metric (binding affinity, probability of binding, probability of immunogenicity, etc.). This filtering of peptide-HLA scores is based on the observation that peptides that are not immunogenic enough for vaccine inclusion may be antigenic (meet the first filtering threshold) and thus recognized by T cell clonotypes expanded by a vaccine. A peptide is antigenic when it is recognized by a T cell receptor and results in a response such as CD8+ T cell cytotoxicity or CD4+ cell activation. Derivatives of an antigenic peptide may be strongly immunogenic, included in a vaccine, and thus activate and expand T cells that recognize the antigenic peptide. The expansion of T cells that recognize an unmodified antigenic peptide can provide an immune response that contributes to disease control. In some embodiments, at the first Peptide Scoring and Score Filtering step in FIGs.1 and 2 the first less constrained threshold for admitting a peptide-HLA score for a peptide for an HLA allele is determined by the best peptide-HLA score of the peptide’s heteroclitic derivatives for the same HLA. In some embodiments, the probability threshold for binding or immunogenicity for a first threshold for a peptide-HLA score may be lower for an HLA allele when the probability of immunogenicity or binding for the peptide’s best derivative is higher for the same HLA. In some embodiments, the product (or other function) of a peptide’s peptide-HLA binding or immunogenicity probability score and the peptide-HLA binding or immunogenicity probability score for its best derivative peptide for the same HLA allele are required to meet a specified threshold (e.g., 0.5, 0.6, 0.7, 0.8, or 0.9). In some embodiments, peptides are scored for third peptide set (Vaccine for Target(s) in FIGs.1 and 2) potential inclusion that have peptide-HLA binding affinities less than about 500 nM. In some embodiments, peptides are selected for the base set that have peptide- HLA binding affinities less than about 1000 nM for at least one HLA allele. Alternatively, predictions of peptide-HLA immunogenicity can be used to qualify target peptides for base set inclusion. In some embodiments, experimental observations of the immunogenicity of peptides in the context of their display by HLA alleles or experimental observation of the binding of - 82 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 peptides to HLA alleles can be used to score peptides for binding to HLA alleles or peptide- HLA immunogenicity. [0512] In some embodiments, experimental observations of the display of peptides by specific HLA alleles in tumor cells can be used to score peptides for peptide-HLA binding or peptide-HLA immunogenicity. In some embodiments, experimental observations of the display of peptides tumor cells by a specific HLA allele can be used to score peptides for peptide-HLA binding or peptide-HLA immunogenicity for that HLA allele. In some embodiments, experimental observations of the display of peptides tumor cells can be used to score peptides for peptide-HLA binding or peptide-HLA immunogenicity, with the HLA allele(s) for a specific observed peptide selected from the HLA alleles present in the tumor that meet a predicted peptide-HLA binding or immunogenicity threshold. In some embodiments, mass spectrometry is used to experimentally determine the display of peptides by tumor cells as described by Bear et al. (2021) or Wang et al. (2019) and these data are used to score for peptide-HLA binding or peptide-HLA immunogenicity. In some embodiments, mass spectrometry is used to experimentally determine the display of peptides by tumor cells, and these experimental data are used to qualify the inclusion of base set (seed set) peptides for one or more HLA alleles for a vaccine. In some embodiments, mass spectrometry is used to experimentally determine the display of a peptide by tumor cells, and these experimental data are used to exclude peptide- HLA binding scores or peptide-HLA immunogenicity scores for the peptide when the peptide is not observed to be displayed by an HLA allele by mass spectrometry. In some embodiments, mass spectrometry is used to experimentally determine the display of peptides by tumor cells in an individual, and these experimental data are used to qualify the inclusion of base set (seed set) peptides for that individual for one or more HLA alleles. In some embodiments, mass spectrometry is used to experimentally determine the display of a peptide by tumor cells in an individual, and these experimental data are used to exclude peptide-HLA binding scores or peptide-HLA immunogenicity scores for the peptide when the peptide is not observed to be displayed by an HLA allele by mass spectrometry. In some embodiments, computational predictions of the immunogenicity of a peptide in the context of display by HLA alleles can used for scoring such as the methods of Ogishi et al. (2019) or Bulik-Sullivan et al. (2019). [0513] In some embodiments, a peptide-HLA score or a peptide-HLA immunogenicity score for a first peptide in the base set (seed set) for a given HLA allele is eliminated and not considered during vaccine design if the wild-type peptide corresponding to the first peptide (e.g., - 83 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 the unmutated naturally occurring form for the peptide or a peptide in the respective species within a defined sequence edit distance) has a peptide-HLA score or a peptide-HLA immunogenicity score for the same HLA allele within a defined threshold. The threshold can be based upon the difference of the scores of the first peptide and the wild-type peptide, the ratio of the scores of the first peptide and the wild-type peptide, the score of the wild-type peptide, or other metrics. The defined threshold can be either greater than or less than a specified value. In some embodiments, the threshold is defined so that the wild-type peptide is not predicted to be presented. In some embodiments, when a peptide-HLA score or peptide-HLA immunogenicity score is eliminated for a first peptide during vaccine design, then peptide-HLA scores or peptide-HLA immunogenicity scores for all of its derivatives (e.g., heteroclitic peptide derivatives) for the same HLA allele are also eliminated and not considered during vaccine design. [0514] In some embodiments, the method further includes running the OptiVax-Robust algorithm as described in Liu et al. (2020a) using the HLA haplotype frequencies of a population on the scored candidate set to construct a base set (also referred to as seed set herein) of target peptides (FIG.2). In some embodiments, HLA diplotype frequencies can be provided to OptiVax. OptiVax-Robust includes algorithms to eliminate peptide redundancy that arises from the sliding window approach with varying window sizes, but other redundancy elimination measures can be used to enforce minimum edit distance constraints between target peptides in the candidate set. The size of the seed set is determined by a point of diminishing returns of population coverage as a function of the number of target peptides in the seed set. Other criteria can also be used, including a minimum number of vaccine target peptides, maximum number of vaccine target peptides, and desired predicted population coverage. In some embodiments, a predetermined population coverage is less than about 0.4, between about 0.4 and 0.5, between about 0.5 and 0.6, between about 0.6 and 0.7, between about 0.7 and 0.8, between about 0.8 and 0.9, or greater than about 0.9. Another possible criterion is a minimum number of expected peptide-HLA binding hits in each individual. In alternate embodiments, the method further includes running the OptiVax-Unlinked algorithm as described in Liu et al. (2020a) instead of OptiVax-Robust. [0515] The OptiVax-Robust method uses binary predictions of peptide-HLA immunogenicity, and these binary predictions can be generated as described in Liu et al. (2020b). The OptiVax-Unlinked method uses the probability of target peptide binding to HLA - 84 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 alleles and can be generated as described in Liu et al. (2020a). In some embodiments, OptiVax- Unlinked and EvalVax-Unlinked are used with the probabilities of peptide-HLA immunogenicity. Either method can be used for the purposes described herein, and thus the term “OptiVax” refers to either the Robust or Unlinked method. In some embodiments, the observed probability of peptide-HLA immunogenicity in experimental assays can be used as the probability of peptide-HLA binding in EvalVax-Unlinked and OptiVax-Unlinked. In some embodiments, the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design describe the world’s population. In alternative embodiments, the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design are specific to a geographic region. In alternative embodiments, the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design are specific to an ancestry. In alternative embodiments, the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design are specific to a race. In alternative embodiments, the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design are specific to individuals with risk factors such as genetic indicators of risk, age, exposure to chemicals, alcohol use, chronic inflammation, diet, hormones, immunosuppression, infectious agents, obesity, radiation, sunlight, or tobacco use. In alternative embodiments, the HLA haplotype or HLA allele frequencies of a population provided to OptiVax for vaccine design are specific to individuals that carry certain HLA alleles. In alternative embodiments, the HLA diplotypes provided to OptiVax for vaccine design describe a single individual, and are used to design an individualized vaccine. [0516] In some embodiments, the base (or seed) set of target peptides (e.g., first peptide set) that results from OptiVax application to the candidate set of target peptides describes a set of unmodified target peptides that represent a possible compact vaccine design (Seed Set in FIG. 2). A base peptide is a target peptide that is included in the base or seed peptide set (e.g., first peptide set). In some embodiments, the seed set (e.g., first peptide set) is based upon filtering candidate peptide scores by predicted or observed affinity or immunogenicity with respect to HLA molecules (Seed Set in FIG.1). However, to improve the display of the target peptides in a wide range of HLA haplotypes as possible, some embodiments include modifications of the seed (or base) set. In some embodiments, experimental assays can be used to ensure that a modified seed (or base) peptide activates T cells that also recognize the base/seed peptide. - 85 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0517] For a given target peptide, the optimal anchor residue selection may depend upon the HLA allele that is binding to and displaying the target peptide and the class of the HLA allele (MHC class I or class II). A seed peptide set (e.g., first peptide set) can become an expanded set by including anchor residue modified peptides of either MHC class I or II peptides (FIGs.1-2). Thus, one aspect of vaccine design is considering how to select a limited set of heteroclitic peptides that derive from the same target peptide for vaccine inclusion given that different heteroclitic peptides will have different and potentially overlapping population coverages. [0518] In some embodiments, all possible anchor modifications for each base set of target peptide are considered. There are typically two anchor residues in peptides bound by MHC class I molecules, typically at positions 2 and 9 for 9-mer peptides. In some embodiments, anchors for 8-mers, 10-mers, and 11-mers are found at positions 2 and n, where n is the last position (8, 10, and 11, respectively). For MHC class I molecules, the last position n is called the “C” position herein for carboxyl terminus. In some embodiments, at each anchor position, 20 possible amino acids are attempted in order to select the best heteroclitic peptides. Thus, for MHC class I binding, 400 (i.e., 20 amino acids by 2 positions = 202) minus 1 heteroclitic peptides are generated for each base target peptide. There are typically four anchor residues in peptides bound by MHC class II molecules, typically at positions 1, 4, 6, and 9 of the 9-mer binding core. Thus, for MHC class II binding there are 160,000 (i.e., 20 amino acids by 4 positions = 204) minus 1 heteroclitic peptides generated for each base target peptide. In some embodiments, more than two (MHC class I) or four (MHC class II) positions are considered as anchors. Other methods, including Bayesian optimization, can be used to select optimal anchor residues to create heteroclitic peptides from each seed (or base) set peptide. Other methods of selecting optimal anchor residues are presented in “Machine learning optimization of peptides for presentation by class II MHCs” by Dai et al. (2020), incorporated in its entirety herein. In some embodiments, the anchor positions are determined by the HLA allele that presents a peptide, and thus the set of heteroclitic peptides includes for each set of HLA specific anchor positions, all possible anchor modifications. [0519] In some embodiments, for all of the target peptides in the base/seed set, new peptide sequences with all possible anchor residue modifications (e.g., MHC class I or class II) are created resulting in a new heteroclitic base set (Expanded set in FIGs.1-2) that includes all of the modifications. In some embodiments, anchor residue modifications of a peptide are not included in the heteroclitic base set if one or more of the peptide’s anchor residue positions - 86 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 contains a substitution mutation that distinguishes the peptide from a self-peptide. In some embodiments, anchor residue modifications of a base/seed peptide are only included in the heteroclitic base set for peptide positions that do not contain a substitution mutation that distinguishes the base/seed peptide from a self-peptide. In some embodiments, anchor residue modifications of a peptide are not included in the heteroclitic base set when one or more of the peptide’s mutations does not occur between a pair of its adjacent anchor residues. In some embodiments, for all of the target peptides in the base/seed set, new peptide sequences with anchor residue modifications (e.g., MHC class I or class II) at selected anchor locations are created resulting in a new heteroclitic base set (Expanded set in FIGs.1-2) that includes the selected modifications. In some embodiments, the anchor residue positions used for modifying peptides are selected from anchor residue positions determined by the HLA alleles considered during vaccine evaluation. In some embodiments, the heteroclitic base set (Expanded set in FIGs.1-2) also includes the original seed (or base) set (Seed Peptide Set in FIGs.1-2). In some embodiments, the heteroclitic base set includes amino acid substitutions at non-anchor residues. In some embodiments, modifications of base peptide residues is accomplished to alter binding to T cell receptors to improve therapeutic efficacy (Candia, et al.2016). In some embodiments, the heteroclitic base set includes amino acid substitutions of non-natural amino acid analogs. The heteroclitic base set is scored for HLA affinity, peptide-HLA immunogenicity, or other metrics as described herein (another round of Peptide Scoring and Score Filtering as shown in FIGs.1- 2). [0520] In some embodiments, the scoring predictions may be further updated for pairs of heteroclitic peptide and HLA allele, eliminating pairs where a heteroclitic peptide has a seed (or base) peptide from which it was derived that is not predicted to be displayed by the HLA allele at a specified threshold of peptide-HLA binding score or a specified peptide-HLA immunogenicity metric. In some embodiments, at the second Peptide Scoring and Score Filtering step in FIGs.1 and 2 a peptide-HLA score is not used for a heteroclitic peptide for a given HLA for vaccine design when the product (or other function) of the heteroclitic peptide’s peptide-HLA immunogenicity or binding probability score and the peptide-HLA immunogenicity or binding probability score for its unmodified counterpart peptide do not meet a specified threshold (e.g., 0.5, 0.6, 0.7, 0.8, or 0.9). In some embodiments, the peptide-HLA scores may also be filtered to ensure that predicted binding cores of the heteroclitic peptide displayed by a particular HLA allele align exactly in position with the binding cores of the respective seed (or base) set target peptide for that HLA allele. In some embodiments, the - 87 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 scoring predictions are filtered for an HLA allele to ensure that the heteroclitic peptides considered for that HLA allele are only modified at anchor positions determined by that HLA allele. Scoring produces a metric of peptide-HLA immunogenicity for peptides and HLA alleles that can be either binary, a probability of immunogenicity, or other metric of immunogenicity such as peptide-HLA affinity or percent rank, and can be based on computational predictions, experimental observations, or a combination of both computational predictions and experimental observations. [0521] In some embodiments, probabilities of peptide-HLA immunogenicity are utilized by OptiVax-Unlinked. In some embodiments, heteroclitic peptides are included in experimental assays such as MIRA (Klinger et al., 2015) or ELISPOT to determine their peptide-HLA immunogenicity metric with respect to specific HLA alleles. In some embodiments, the methods of Liu et al. (2020b), can be used to incorporate MIRA data for heteroclitic peptides into a model of peptide-HLA immunogenicity. In some embodiments, peptide-HLA immunogenicity metrics of heteroclitic peptides are experimentally determined and their ability to activate T cells that also recognize the corresponding seed (or base) peptide of the heteroclitic peptide is performed as is known in the art to qualify the heteroclitic peptide for vaccine inclusion (e.g., Houghton et al., 2007). In some embodiments, these assays of the immunogenicity and cross-reactivity of heteroclitic peptides are performed when the heteroclitic peptides are displayed by specific HLA alleles. [0522] In some embodiments, experimental observations of the display of heteroclitic peptides by specific HLA alleles in cells can be used to score peptides for peptide-HLA binding or peptide-HLA immunogenicity. In some embodiments, mass spectrometry is used to experimentally determine the display of heteroclitic peptides by cells as described by Bear et al. (2021) or Wang et al. (2019) and these data are used to score for peptide-HLA binding or peptide-HLA immunogenicity. In some embodiments, mass spectrometry is used to experimentally determine the display of heteroclitic peptides by cells, and these experimental data are used to qualify the inclusion of heteroclitic peptides for inclusion in a vaccine. In some embodiments, mass spectrometry is used to experimentally determine the display of a peptide by tumor cells, and these experimental data are used to exclude peptide-HLA binding scores or peptide-HLA immunogenicity scores for the peptide when the peptide is not observed to be displayed by an HLA allele by mass spectrometry. In some embodiments, mass spectrometry is used to experimentally determine the display of a heteroclitic peptide by cells with an HLA - 88 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 allele found in an individual, and these experimental data are used to qualify the inclusion of the heteroclitic peptide for inclusion in a vaccine for the individual. In some embodiments, mass spectrometry is used to experimentally determine the display of a peptide by tumor cells in an individual, and these experimental data are used to exclude peptide-HLA binding scores or peptide-HLA immunogenicity scores for the peptide when the peptide is not observed to be displayed by an HLA allele by mass spectrometry. In some embodiments, computational predictions of the immunogenicity of a heteroclitic peptide in the context of display by HLA alleles can used for scoring such as the methods of Ogishi et al. (2019) or Bulik-Sullivan et al. (2019). [0523] In some embodiments, a peptide in the heteroclitic base set is removed if (1) one of its anchor positions for an HLA allele corresponds to the location of a mutation in the base/seed peptide from which it was derived that distinguishes the base/seed peptide from a self-peptide, and (2) if the peptide-HLA binding or peptide-HLA immunogenicity of the self-peptide is stronger than a specified threshold for self-peptide binding or immunogenicity. This eliminates peptides in the heteroclitic base set that may cross-react with self-peptides as a result of sharing TCR facing residues with self-peptides. In some embodiments, the threshold for self-peptide binding is between approximately 500 nM to 1000 nM. [0524] In some embodiments, redundant peptides in the heteroclitic base set are removed. In some embodiments, a redundant peptide is a first heteroclitic peptide that has peptide-HLA immunogenicity scores or peptide-HLA binding scores that are less immunogenic for all scored HLAs than a second heteroclitic peptide in the heteroclitic base set, where both the first and second heteroclitic peptides are derived from the same base (or seed) peptide. In some embodiments, peptide redundancy is determined by only comparing peptide-HLA immunogenicity scores or peptide-HLA binding scores for HLA alleles where the peptide-HLA immunogenicity scores or peptide-HLA binding scores for both peptides for an HLA allele are more immunogenic than a given threshold (e.g., 50 nM for binding). In some embodiments, a redundant peptide is a first heteroclitic peptide that has an average peptide-HLA immunogenicity score or peptide-HLA binding score that is less immunogenic than the average peptide-HLA immunogenicity score or peptide-HLA binding score of a second heteroclitic peptide in the heteroclitic base set, where both the first and second heteroclitic peptides are derived from the same base (or seed) peptide, and the average scores are computed for HLA alleles where the peptide-HLA immunogenicity scores or peptide-HLA binding scores for both - 89 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 peptides for an HLA allele are more immunogenic than a given threshold (e.g., 50 nM for binding). In some embodiments, a redundant peptide is a first heteroclitic peptide that has a weighted peptide-HLA immunogenicity score or peptide-HLA binding score that is less immunogenic than the weighted peptide-HLA immunogenicity score or peptide-HLA binding score of a second heteroclitic peptide in the heteroclitic base set, where both the first and second heteroclitic peptides are derived from the same base (or seed) peptide, and where the weighting is determined by the frequency of the HLA allele in a human population, and the weighted scores are computed for HLA alleles where the peptide-HLA immunogenicity scores or peptide- HLA binding scores for both peptides for an HLA allele are more immunogenic that a given threshold (e.g., 50 nM for binding). [0525] In some embodiments, the next step involves scoring the heteroclitic base set (the second peptide set) and filtering the resulting scores to create a second peptide set by comparing the peptide-HLA immunogenicity scores or peptide-HLA binding scores of the peptides for one or more HLA alleles to a threshold. In some embodiments, an affinity criterion of about 50 nM is used to increase the probability that a vaccine peptide will be found and displayed by HLA molecules. In some embodiments, the affinity criteria is more constrained than 50 nM (i.e., < 50 nM). In some embodiments, the affinity criteria is more constrained than about 500 nM (i.e., < 500 nM). In some embodiments, individual peptide-HLA binding scores or immunogenicity metrics are determined and thus a peptide may be retained as long as it meets the criteria for at least one HLA allele, and only peptide-HLA scores that meet the criteria are considered for vaccine design. [0526] In some embodiments, probabilistic thresholds are used in the peptide scoring and score filtering steps (FIGs.1-2) to filter peptide-HLA combinations for vaccine design. In some embodiments, a credence function is used to predict the probability of peptide-HLA display or peptide-HLA immunogenicity for each peptide for a desired set of HLA alleles. In some embodiments, a credence function implementation fits the output of a binding prediction algorithm (such the EL or BA output of NetMHCpan4.1 or NetMHCIIpan4.0) to observed held- out binding or immunogenicity data. One implementation of credence functions is described in Dai, Z., & Gifford, D. “Constrained Submodular Optimization for Vaccine Design”. arXiv preprint arXiv:2206.08336. https://arxiv.org/abs/2206.08336, Version 2, 27 January 2023. Held-out data is experimental data that is not used to train the binding prediction algorithm. In some embodiments, held-out data contains examples of experimentally verified peptide-HLA - 90 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 binding or immunogenicity. In some embodiments, held-out data describes known peptide-HLA binding pairs, and peptides surrounding known binders in these held-out data are used to generate negative examples of binding which is added to the held-out data. The credence function that maps the output of a prediction algorithm to a probability of binding (or immunogenicity) is selected to minimize the difference between the output of the prediction algorithm on peptides examples in the held-out data and the experimentally observed binding (or immunogenicity) in the held-out data. For example, when the held-out data contains an experimentally verified peptide-HLA binding pair, the output of the credence function should assign this peptide-HLA pair a high probability of binding. In some embodiments, this is accomplished by dividing the output of the prediction algorithm into discrete intervals (“bins”) and for each bin choosing a function that maps the output of the prediction algorithm that are contained in that bin into the observed fraction of binding (or immunogenicity) in the held-out experimental data. In some embodiments, the functions for each interval are chosen so that increasing intervals have increasing probabilities of binding (or immunogenicity). In some embodiments, the process of fitting a credence function is repeated on different sets of held-out data, and the difference between the credence functions on each set of held-out data is used to validate the accuracy of the credence function. [0527] In some embodiments, the first peptide scoring and filtering step uses a credence function to predict the probability of binding (or immunogenicity) for all combinations of candidate peptides and HLA alleles. In some embodiments, the first peptide scoring and filtering step eliminates peptide-HLA combinations that do not bind (or are not immunogenic) stronger than a probability threshold for the respective HLA allele. In some embodiments, the second peptide scoring and filtering step eliminates peptide-HLA combinations where (1) the peptide’s corresponding base peptide-HLA combination was eliminated in the first peptide scoring and filtering step, or (2) the peptide-HLA combination does not have a probability greater than a second more stringent probability threshold. In some embodiments, the second peptide scoring and filtering step uses a function to combine the peptide-HLA display (or immunogenicity) probability of a base peptide with the peptide-HLA display (or immunogenicity) probability of its heteroclitic derivative, and the result of the function must be greater than a threshold to keep the peptide-HLA combination for the heteroclitic derivative. In some embodiments, the combination function is multiplication. In some embodiments, the result of the combination function is used as the peptide-HLA metric for that peptide for vaccine design. - 91 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0528] In some embodiments, the next step involves inputting the second peptide set to OptiVax to select a compact set of vaccine peptides that maximizes predicted vaccine performance (Vaccine Performance Optimization; FIGs.1-2). In some embodiments, predicted vaccine performance is a function of expected peptide-HLA binding affinity (e.g., a function of the distribution of peptide-HLA binding affinities across all peptide-HLA combinations for a given peptide set, or weighted by the occurrence of the HLA alleles in a population or individual). In some embodiments, predicted vaccine performance is the expected population coverage of a vaccine. In some embodiments, predicted vaccine performance is the expected number peptide-HLA hits produced by a vaccine in a population or individual. In some embodiments, predicted vaccine performance requires a minimum expected number of peptide- HLA hits (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more) produced by a vaccine. In some embodiments, predicted vaccine performance is a function of population coverage and expected number of peptide-HLA hits desired produced by a vaccine. In some embodiments, predicted vaccine performance is a metric that describes the overall immunogenic properties of a vaccine where all of the peptides in the vaccine are scored for peptide-HLA immunogenicity for two or more HLA alleles (e.g., three or more HLA alleles). In some embodiments, predicted vaccine performance excludes immunogenicity contributions by selected HLA alleles above a maximum number of peptide-HLA hits (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more). In some embodiments, predicted vaccine performance excludes immunogenicity contributions of individual HLA diplotypes above a maximum number of peptide-HLA hits (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more). In some embodiments, predicted vaccine performance is the fraction of covered HLA alleles, which is the expected fraction of HLA alleles in each individual that have a minimum number of peptides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more) with predicted peptide-HLA immunogenicity produced by a vaccine. In some embodiments, predicted vaccine performance is the expected fraction of HLA alleles in a single individual that have a minimum number of peptides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more) with predicted peptide-HLA immunogenicity produced by a vaccine. [0529] In some embodiments, a vaccine is designed by the iterative selection of peptides from the heteroclitic base set (also referred to as Expanded set as shown in FIGs.1-2) at progressively less stringent criteria for predicted peptide immunogenicity or display. In some embodiments, a peptide is retained if at least one of its peptide-HLA scores is not eliminated by the thresholds employed. In some embodiments, OptiVax is first used to design a vaccine with a desired vaccine performance with specific peptide qualification criteria (e.g., seed HLA-peptide scores from the candidate set must bind to at least one MHC molecule at 500 nM or stronger, - 92 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 and peptide-HLA scores from the expanded set must bind to at least one MHC molecule at 50 nM or stronger). The vaccine that results from this application of OptiVax is then used as the foundation for vaccine augmentation with less stringent criteria (e.g., seed peptide-HLA scores from the candidate set must bind to at least one MHC molecule at 1000 nM or stronger, and peptide HLA-scores from the expanded set must bind to at least one MHC molecule at 100 nM or stronger) to further improve the desired vaccine performance. Methods for vaccine augmentation are described in Liu et al. (2020b), incorporated by reference in its entirety herein. In some embodiments, multiple rounds of vaccine augmentation may be utilized. In some embodiments, the final augmented vaccine is the one selected. [0530] In some embodiments, selection of peptide sets to meet a desired predicted vaccine performance can be accomplished by computational algorithms other than OptiVax. In some embodiments, integer linear programming or mixed-integer linear programming is employed for selecting peptide sets instead of OptiVax. One example of an integer programming method for peptide set selection is described by Toussaint et al., 2008, incorporated by reference in its entirety herein. An example solver for mixed-integer linear programming is Python-MIP that can be used in conjunction with Toussaint et al., 2008. A second example of methods for vaccine peptide selection is described in “Maximum n-times Coverage for Vaccine Design” by Liu et al. (2021), incorporated by reference in its entirety herein. [0531] Predicted vaccine performance refers to a metric. Predicted vaccine performance can be expressed as a single numerical value, a plurality of numerical values, any number of non- numerical values, and a combination thereof. The value or values can be expressed in any mathematical or symbolic term and on any scale (e.g., nominal scale, ordinal scale, interval scale, or ratio scale). [0532] A seed (or base) peptide and all of the modified peptides that are derived from that seed (or base) peptide comprise a single peptide family. In some embodiments, in the component of vaccine performance that is based on peptide-HLA immunogenicity for a given HLA allele, a maximum number of peptides (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more) that are in the same peptide family are given computational immunogenicity credit for that HLA allele. This limit on peptide family immunogenicity limits the credit caused by many modified versions of the same base peptide. In some embodiments, the methods described herein are included for running OptiVax with an EvalVax objective function that corresponds to a desired metric of predicted vaccine performance. In some embodiments, population coverage means the - 93 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 proportion of a subject population that presents one or more immunogenic peptides that activate T cells responsive to a seed (or base) target peptide. The metric of population coverage is computed using the HLA haplotype frequency in a given population such as a representative human population. In some embodiments, the metric of population coverage is computed using marginal HLA frequencies in a population. Maximizing population coverage means selecting a peptide set (either a base peptide set, a modified peptide set, or a combination of base and modified peptides; e.g., a first peptide set, second peptide set, or third peptide set) that collectively results in the greatest fraction of the population that has at least a minimum number (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more) of immunogenic peptide-HLA bindings based on proportions of HLA haplotypes in a given population (e.g., representative human population). In some embodiments, this process includes the OptiVax selection of heteroclitic peptides (as described in this disclosure) that activate T cells that respond to their corresponding seed (or base) peptide and the heteroclitic base peptides to improve population coverage. In some embodiments, the seed (or base) target peptides are always included in the final vaccine design. In some embodiments, peptides are only considered as candidates for a vaccine design (e.g., included in a first, second, and/or third peptide set) if they have been observed to be immunogenic in clinical data, animal models, or tissue culture models. In some embodiments, vaccine peptides are selected to be displayed by a peptide specific set of HLA class I or class II alleles, wherein for at least two peptides in a vaccine all of the peptide specific sets of HLA class I or class II alleles are not identical. [0533] Although heteroclitic peptides are used as exemplary embodiments in this disclosure, any modified peptide could be used in place of a heteroclitic peptide. A modified peptide is a peptide that has one or more amino acid substitutions of a target base/seed peptide. The amino acid substitution could be located at an anchor position or any other non-anchor position. [0534] In some embodiments, a candidate vaccine peptide (e.g., a base peptide or a modified peptide) is eliminated from vaccine inclusion if it activates T cells that recognize self-peptides (e.g., this can be achieved at the first and/or second round of Peptide Filtering and Sorting as shown in FIGs.1-2). In some embodiments, a candidate vaccine peptide (e.g., a base peptide or a modified peptide) is computationally eliminated from vaccine inclusion if its outward facing amino acids, when bound by an HLA allele, are similar to outward facing self-peptide residues that are presented by the same HLA allele, where similarity can be defined by identity or similarity metrics such as BLOSUM matrices (BLOSUM matrices are known in the art). In - 94 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 some embodiments, calculation of the percent identity of two nucleic acid or polypeptide sequences, for example, can be performed by aligning the two sequences for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second sequences for optimal alignment and non-identical sequences can be disregarded for comparison purposes). The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. In one embodiment, the percent identity between two protein sequences can be determined by aligning the proteins and then computing the percentage of residues that are identical as described in Wang et al. (BMC Bioinformatics 19, 529 (2018). [0535] Testing a vaccine peptide for its ability to activate T cells that recognize self-peptides can be experimentally accomplished by the vaccination of animal models followed by ELISPOT or other immunogenicity assay or with human tissue protocols. In both cases, models with HLA alleles that present the vaccine peptide are used. In some embodiments, human primary blood mononuclear cells (PBMCs) are stimulated with a vaccine peptide, the T cells are allowed to grow, and then T cell activation with a self-peptide is assayed as described in Tapia-Calle et al. (2019) or other methods as known in the art. In some embodiments, the vaccine peptide is excluded from vaccine inclusion if the T cells are activated by the self-peptide. In some embodiments, computational predictions of the ability of a peptide to activate T cells that also recognize self-peptides can be utilized. These predictions can be based upon the modeling of the outward facing residues from the peptide-HLA complex and their interactions with other peptide residues. In some embodiments, a candidate vaccine peptide (e.g., a base peptide or a modified peptide) is eliminated from vaccine inclusion or experimentally tested for cross-reactivity if it is predicted to activate T cells that also recognize self-peptides based upon the structural similarity of the peptide-MHC complex of the candidate peptide (e.g., a base peptide or a modified peptide) and the peptide-MHC complex of a self-peptide. One method for the prediction of peptide-MHC structure is described by Park et al. (2013). [0536] In some embodiments, the peptide-HLA binding score or peptide-HLA immunogenicity metric for a candidate heteroclitic vaccine peptide (e.g., a modified peptide) and HLA allele is eliminated from consideration during vaccine design if the candidate heteroclitic vaccine peptide does not activate T cells that recognize its corresponding base/seed target peptide (second round of Peptide Scoring and Score Filtering, FIGs.1-2) for the given HLA allele. In some embodiments, a heteroclitic vaccine peptide (e.g., a modified peptide) is - 95 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 eliminated from a vaccine design if the candidate heteroclitic vaccine peptide does not activate T cells that recognize its corresponding base/seed target peptide (second round of Peptide Scoring and Score Filtering, FIGs.1-2) for a given HLA allele. Testing a candidate heteroclitic peptide (e.g., a modified peptide) for its ability to activate T cells that recognize its corresponding seed (or base) target peptide with respect to the same HLA allele can be experimentally accomplished by the vaccination of animal models followed by ELISPOT or other immunogenicity assay or with human tissue protocols. In both cases, models with HLA alleles that present the heteroclitic peptide are used. In some embodiments, human PBMCs are stimulated with the heteroclitic peptide, the T cells are allowed to grow, and then T cell activation with the seed (or base) target peptide is assayed as described in Tapia-Calle et al. (2019) or using other methods known in the art. In some embodiments, computational predictions of the ability of a heteroclitic peptide to activate T cells that also recognize the corresponding seed (or base) target peptide can be utilized. These predictions can be based upon the modeling of the outward facing residues from the peptide-HLA complex and their interactions with other peptide residues. In some embodiments, the structural similarity of the peptide-HLA complex of a heteroclitic peptide and the peptide-HLA complex of the corresponding seed (or base) target is used to qualify heteroclitic peptides for vaccine inclusion or to require experimental immunogenicity testing before vaccine inclusion. [0537] TCR Interface Divergence (TCRID) is the Least Root Mean Square Deviation of the difference between a first peptide’s TCR facing residues’ 3D positions and the corresponding residue positions of a second peptide with respect to a specific HLA allele. In some embodiments, other metrics are used for the TCRID instead of Least Root Mean Square Deviation. In some embodiments, other metrics are used for the TCRID that include position deviations in non-TCR facing residues and MHC residues from the specific HLA allele. In some embodiments, TCRID is used to predict if two peptides when displayed by a given HLA allele will activate the same T cell clonotypes. In some embodiments, FlexPepDock (London et al., 2011, incorporated by reference in its entirety herein) or DINC (Antunes et al., 2018, incorporated by reference in its entirety herein) in conjunction with the crystal structures of HLA molecules can be used to compute TCRID metrics for pairs of peptides given an HLA molecule. In some embodiments, TCRID is computed by (1) determining the 3D peptide-HLA structures for two different peptides bound by a specific HLA allele, (2) aligning the HLA alpha helices of the peptide-HLA structures, and (3) computing the Least Root Mean Square Deviation of the - 96 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 difference between the TCR facing residues of the two peptides with respect to the aligned alpha helix reference frame. [0538] In some embodiments, the second Peptide Scoring and Score Filtering step in FIGs.1 and 2 will eliminate the peptide-HLA binding or immunogenicity score for a heteroclitic peptide for a specific HLA allele when the HLA specific TCRID between the heteroclitic peptide and its corresponding base (or seed) peptide from which it was derived is over a first TCRID threshold. In some embodiments, the second Peptide Scoring and Score Filtering step in FIGs.1 and 2 will eliminate all peptide-HLA binding or immunogenicity scores for a heteroclitic peptide when the HLA specific TCRID between the heteroclitic peptide and its corresponding unmutated self- peptide from which it was derived is under a second TCRID threshold. In some embodiments, the first Peptide Scoring and Score Filtering step in FIGs.1 and 2 will eliminate all peptide-HLA binding or immunogenicity scores for a candidate peptide when the HLA specific TCRID between the peptide and its corresponding unmutated self-peptide is under a third TCRID threshold. In some embodiments, any of the TCRID thresholds are determined by experimentally observing or computationally predicting the cross-reactivity of TCR molecules to peptide-HLA complexes. [0539] FIG.3 (MHC class I) and FIG.4 (MHC class II) show the predicted population coverage of OptiVax-Robust selected single target-specific vaccines with differing number of peptides designed for selected mutations in the BRAF, CTNNB1, KRAS, PIK3CA, and TP53 genes. FIGs.3-4 show that as the number of peptides increases for a vaccine, its predicted population coverage increases. The population coverage shown in FIGs.3-4 are of those individuals that have the specific mutation that the vaccine is designed to cover. An increase in peptide count will also typically cause the average number of peptide-HLA hits in each individual to increase in the population. [0540] OptiVax can be used to design a vaccine to maximize the fraction/proportion of the population whose HLA molecules are predicted to bind to and display at least p peptides from the vaccine. In some embodiments, this prediction (e.g., scoring) includes experimental immunogenicity data to directly predict at least p peptides will be immunogenic. The number p is input to OptiVax, and OptiVax can be run multiple times with varying values for p to obtain a predicted optimal target peptide set for different peptide counts p. Larger values of p will increase the redundancy of a vaccine at the cost of more peptides to achieve a desired population coverage. In some embodiments, it may not be possible to achieve a given population coverage - 97 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 given a specific heteroclitic base set. In some embodiments, the number p is a function of the desired size of a vaccine. [0541] The methods described herein can be used to design separate vaccine formulations for MHC class I and class II-based immunity. [0542] In some embodiments, this procedure is used to create a vaccine for an individual. In some embodiments, the target peptides present in the individual are determined by sequencing the individual’s tumor RNA or DNA, and identifying mutations that produce foreign peptides. One embodiment of this method is described in U.S. Patent No.10,738,355, incorporated by reference in its entirety herein. In some embodiments, peptide sequencing methods are used to identify target peptides in the individual. One embodiment of this is described in U.S. Patent Publication No.2011/0257890. In some embodiments, the target peptides used for the individual’s vaccine are selected when a self-peptide, foreign peptide, pathogen peptide or RNA encoding a self-peptide, foreign peptide, or pathogen peptide observed in a specimen from the individual is present at a predetermined level. The target peptides in the individual are used to construct a vaccine as disclosed herein. For vaccine design, OptiVax is provided a diplotype comprising the HLA type of the individual. In an alternative embodiment, the HLA type of an individual is separated into multiple diplotypes with frequencies that sum to one, where each diplotype comprises one or more HLA alleles from the individual and a notation that the other allele positions should not be evaluated. The use of multiple diplotypes will cause OptiVax’s objective function to increase the chance that immunogenic peptides will be displayed by all of the constructed diplotypes. This achieves the objective of maximizing the number of distinct HLA alleles in the individual that exhibit peptide-HLA immunogenicity and thus improves the allelic coverage of the vaccine in the individual. [0543] FIG.5 shows the predicted vaccine performance (predicted number of peptide-HLA hits) of ten example G12V MHC class I vaccines for a single individual with the MHC class I HLA diplotype HLA-A02:03, HLA-A11:01, HLA-B55:02, HLA-B58:01, HLA-C03:02, HLA- C03:03. OptiVax was used to design ten G12V MHC class I vaccines for this HLA diplotype with peptide counts ranging from 1 to 10. For the results in FIG.5, OptiVax was run with six synthetic diplotypes, each equally weighted, each with one HLA allele from the individual’s HLA diplotype, and the other allele positions marked to not be evaluated. - 98 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 MHC Class I Vaccine Design Procedure [0544] In some embodiments, MHC class I vaccine design procedures consist of the following computational steps. [0545] In some embodiments, the inputs for the computation are: sequence (length n) containing the neoantigen(s) or pathogenic target(s) of interest (e.g., KRAS G12D, KRAS G12V, KRAS G12R, KRAS G12C, KRAS G13D). ^^^ denotes the amino acid at position i. t: Position of target mutation in ^^, ^^ ∈ ^1, … ^^^ (e.g., t = 12 for KRAS G12D). s: Substitution mutation ^^ ∈ ^ ^^ ^^ ^^ ^^, ^^ ^^ ^^ ^^ ^^^ is true if the mutation is a substitution, and false if the mutation is a deletion or insertion or the peptide does not contain a mutation (such as in pathogen targets). When the mutation is a deletion or insertion then t indicates the position immediately before the deletion or insertion. ^^^: Threshold for potential presentation of peptides by MHC for peptide-MHC scoring (e.g., 500 nM binding affinity) ^^ଶ: Threshold for predicted display of peptides by MHC for peptide-MHC scoring (e.g., 50 nM binding affinity) ℋ: Set of HLA alleles (for HLA-A, HLA-B, HLA-C loci) F: ℝ: Population haplotype frequencies (for OptiVax optimization and coverage evaluation). N: Parameter for EvalVax and OptiVax objective function. Specifies minimum number of predicted per-individual hits for population coverage objective to consider the individual covered. Default = 1 (computes P(n ≥ 1) population coverage). [0546] In some embodiments, Peptide-HLA Scoring Functions used are: ScorePotential : ^^ ×
ℝ: Scoring function mapping a (peptide, HLA allele) pair to a prediction of peptide-HLA display. If predicted affinity ≤ τ1, then returns 1, else returns 0. Options include MHCflurry, NetMHCpan, PUFFIN, ensembles, or alternative metrics or software may be used, including models calibrated against immunogenicity data. SCOREDISPLAY : ^^ × ℋ → ℝ: Scoring function mapping a (peptide, HLA allele) pair to a prediction of peptide-HLA display. If predicted affinity ≤ τ2, then returns 1, else returns 0. - 99 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 Options include MHCflurry, NetMHCpan, PUFFIN, ensembles, or alternative metrics or software may be used, including models calibrated against immunogenicity data. [0547] Next, from the seed protein sequence (P), a set ^^ of windowed native peptides spanning the protein sequence(s) is constructed. ^^^…^ା(^ି^) only produces set members when the subscripts are within the range of the defined seed protein P. In some embodiments, 8-mers, 9-mers, 10-mers, and 11-mers are produced, but this process can be performed with any desired window lengths and the resulting peptide sets combined. In some embodiments, only 9-mers are produced. ^^ = ^ ^^^ ^∈^଼,…,^^^ ^^^ ^
1 ^ [0548] The second condition j ≠ {t – (k-1), t – 1} excludes peptides where the mutation at t is in positions P2 or Pk of the windowed k-mer peptide (i.e., the anchor positions) and the mutation is a substitution. MHC Class I Vaccine Design Procedure with Defined Peptide Set ^^ [0549] Next, each peptide sequence in ^^ is scored against all HLA alleles in ℋ for potential presentation using SCOREPOTENTIAL (with threshold τ1 = 500 nM) and store results in a | ^^| × |ℋ| matrix S: S[p, h] = SCOREPOTENTIAL(p, h) ∀ p ∈ ^^, h ∈ ℋ Note that S is a binary matrix where 1 indicates the HLA is predicted to potentially present the peptide, and 0 indicates no potential presentation. Define base set of peptides ^^ ⊆ ^^: ^^ = ^ ^^ ∈ ^^ | ∃ℎ s. t. ^^^ ^^,ℎ^ = 1^ Thus, B contains the native peptides that are predicted to be potentially presented by at least 1 HLA. - 100 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 Create a set of all heteroclitic peptides B' stemming from peptides in B:
where ANCHOR-MODIFIED(b) returns a set of all 399 anchor-modified peptides stemming from b (with all possible modifications to the amino acids at P2 and P9). [0550] Next, all heteroclitic candidate peptides (e.g., modified peptides) in B' are scored against all HLA alleles in ℋ for predicted display using SCOREDISPLAY (with threshold τ2 = 50 nM), and store results in binary |B'| × |ℋ| matrix ^^^ ᇱ: ^^^ ᇱ^ ^^ᇱ,ℎ^ = SCOREDISPLAY( ^^ᇱ,ℎ) ∀ ^^ᇱ ∈ ^^ᇱ,ℎ ∈ ℋ [0551] Next, an updated scoring matrix ^^ଶ ᇱ is computed for heteroclitic peptides conditioned on the potential presentation of the corresponding base peptides by each HLA: ^^ᇱ ^^ ^^ᇱ, ℎ^, if ^^^ ^^,ℎ^ = 1
0, otherwise ∀ ^^ ᇱ ∈ ^^ ᇱ ,ℎ ∈ ℋ where each heteroclitic peptide b' ∈ B' is a mutation of base peptide b ∈ B. This condition enforces that if h was not predicted to potentially present b, then all heteroclitic peptides b' derived from b will not be displayed by h (even if h would otherwise be predicted to display b'). [0552] In some embodiments, OptiVax-Robust is used to design a final peptide set (e.g., third peptide set) from the union of base peptides and heteroclitic peptides B ∪ B' (with corresponding scoring matrices S and ^^ଶ ᇱ for B and B', respectively). OptiVax will output m sets ^^^ for s ∈ [1, …, m] where m is the largest vaccine size requested from OptiVax. Let ^^^ denote the compact set of vaccine peptides output by OptiVax containing k peptides. Note that ^^^ା^ is not necessarily a superset of ^^^. In alternate embodiments, OptiVax can be used to augment the base set B with peptides from B' using scoring matrix ^^ଶ ᇱ to have OptiVax return set ^^^, and the final vaccine set
of peptides ^^ ∪ ^^^. [0553] In some embodiments, this procedure is repeated independently for each target of interest, and the resulting independent vaccine sets can be merged into a combined vaccine as described below. - 101 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 MHC Class II Vaccine Design Procedure [0554] In some embodiments, MHC class II vaccine design procedures consist of the following computational steps. [0555] In some embodiments, the inputs for the computation are: sequence(s) (length n) containing the neoantigen(s) or pathogenic target(s) of interest (e.g., KRAS G12D, KRAS G12V, KRAS G12R, KRAS G12C, KRAS G13D). Pi denotes the amino acid at position i. t: Position of target mutation in P, t ∈ [1,…,n] (e.g., t = 12 for KRAS G12D). s: Substitution mutation ^^ ∈ ^ ^^ ^^ ^^ ^^, ^^ ^^ ^^ ^^ ^^^ is true if the mutation is a substitution, and false if the mutation is a deletion or insertion or the peptide does not contain a mutation (such as for pathogen targets). When the mutation is a deletion or insertion then t indicates the position immediately before the deletion or insertion. ^^^: Threshold for potential presentation of peptides by MHC for peptide-MHC scoring (e.g., 500 nM binding affinity) ^^ଶ: Threshold for predicted display of peptides by MHC for peptide-MHC scoring (e.g., 50 nM binding affinity) ℋ: Set of HLA alleles (for HLA-DR, HLA-DQ, HLA-DP loci) F : ℋଷ → ℝ: Population haplotype frequencies (for OptiVax optimization and coverage evaluation). N: Parameter for EvalVax and OptiVax objective function. Specifies minimum number of predicted per-individual hits for population coverage objective to consider the individual covered. Default = 1 (computes P(n ≥ 1) population coverage). [0556] In some embodiments, Peptide-HLA Scoring Functions used are: SCOREPOTENTIAL : ^^ × ℋ → ℝ: Scoring function mapping a (peptide, HLA allele) pair to a prediction of display. If predicted affinity ≤ τ1 , then returns 1, else returns 0. Options include NetMHCIIpan, PUFFIN, ensembles, or alternative metrics or software may be used, including models calibrated against immunogenicity data. SCOREDISPLAY : ^^ × ℋ → ℝ: Scoring function mapping a (peptide, HLA allele) pair to a prediction of peptide-HLA display. If predicted affinity ≤ τ2 , then returns 1, else returns 0. - 102 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 Options include NetMHCIIpan, PUFFIN, ensembles, or alternative metrics or software may be used, including models calibrated against immunogenicity data. FindCore : ^^ × ℋ → [1, ... , ^^]: Function mapping a (peptide, HLA allele) pair to a prediction of the 9-mer binding core. The core may be specified as the offset position (index) into the peptide where the core begins. [0557] Next, from the seed protein sequence (P), a set ^^ of peptides spanning the protein sequence are constructed.
only produces set members when the subscripts are within the range of the defined seed protein P. Here, we extract all windowed peptides of length 13–25 spanning the target mutation, but this process can be performed using any desired window lengths (e.g., only 15-mers).
^ where ^^^ contains all sliding windows of length k, which are combined to form ^^. Note that here (unlike MHC class I), no peptides are excluded based on binding core or anchor residue positions (for MHC class II, filtering is performed as described in this disclosure). MHC Class II Vaccine Design Procedure with Defined Peptide Set ^^ [0558] Next, each peptide sequence in ^^ is scored against all HLA alleles in ℋ for potential presentation using SCOREPOTENTIAL (with threshold τ1 = 500 nM) and store results in a | ^^| × | ℋ| matrix S1: S1[p, h] = SCOREPOTENTIAL(p, h) ∀ p ∈ ^^, h ∈ ℋ Note that S1 is a binary matrix where 1 indicates the HLA is predicted to potentially present the peptide, and 0 indicates no potential presentation. [0559] For each (peptide, HLA allele) pair (p, h), identify/predict the 9-mer binding core using FINDCORE. The predicted binding core is recorded in a matrix C: C[p, h] = FINDCORE(p, h) ∀ p ∈ ^^, h ∈ ℋ [0560] Next, if not(s) then S2[p, h] = S1[p, h] otherwise an updated scoring matrix S2 is computed for native peptides in ^^: - 103 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 ^^ଶ[ ^^, ℎ] = ^ ^^^[ ^^, ℎ], if ^^[ ^^, ℎ] specifies ^^௧ at a non − anchor position inside 0, otherwise
ℋ where Pt is the target residue of interest (e.g., the mutation site of KRAS G12D). This condition enforces the target residue to fall within the binding core at a non-anchor position for all (peptide, HLA allele) pairs with non-zero scores in S2 and allows the binding core to vary by allele per peptide (as the binding cores of a particular peptide may differ based on the HLA allele presenting the peptide). Thus, for each pair (p, h), if the predicted binding core C[p, h] specifies the target residue Pt at an anchor position (P1, P4, P6, or P9 of the 9-mer core), or if Pt is not contained within the binding core, then S2 [p, h] = 0. In an alternate embodiment, Pt can be located outside of the core or inside the core in a non-anchor position. In some embodiments, Pt can only be located at specific positions inside and/or outside of the core. In some embodiments, the binding core predictions in C are accompanied by prediction confidences. In some embodiments, if the confidence for predicted core C[p, h] is below a desired threshold (e.g., 0.5, 0.6, 0.7, 0.8, or 0.9), then S2 [p, h] = 0. [0561] Next, OptiVax-Robust is run with peptides ^^ and scoring matrix S2 to identify a non- redundant base set of peptides B ⊆ ^^. (In alternate embodiments, B can be chosen as the entire set ^^ rather than identifying a non-redundant base set.) [0562] Next, a set of all heteroclitic peptides B' is created stemming from peptides in B: ^^ᇱ 1}
where ANCHOR-MODIFIED(b,c) returns a set of all 204 – 1 anchor-modified peptides stemming from b with all possible modifications to the amino acids at P1, P4, P6, and P9 of the 9-mer binding core c. Thus, for each base peptide b, the heteroclitic set B' contains all anchor-modified peptides b' with modifications to all unique cores of b identified for any HLA alleles that potentially present b with a valid core position as indicated by scoring matrix S2. [0563] Next, all heteroclitic candidate peptides (e.g., modified peptides) in B' are scored against all HLA alleles in ℋ for predicted display using SCOREDISPLAY (with threshold τ2 = 50 nM), and store results in binary |B'| × |ℋ| matrix ^^^ ᇱ: ^^^ ᇱ[ ^^ᇱ, ℎ] = ScoreDisplay( ^^ᇱ,ℎ) ∀ ^^ᇱ ∈ ^^ᇱ,ℎ ∈ ℋ - 104 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0564] For each (heteroclitic peptide, HLA allele) pair (b',h), identify/predict the 9-mer binding core using FINDCORE. The predicted binding core is recorded in a matrix C': ^^ ᇱ[ ^^ ᇱ ,ℎ ] = FINDCORE ( ^^ ᇱ , ℎ ) ∀ ^^ ᇱ ∈ ^^ ᇱ ,ℎ ∈ ℋ [0565] An updated scoring matrix ^^ଶ ᇱ is computed for heteroclitic peptides conditioned on the identified binding cores of a heteroclitic and base peptides occurring at the same offset by a particular HLA: ^^ଶ ᇱ ℋ
where each heteroclitic peptide b' ∈ B' is a mutation of base peptide b ∈ B. This condition enforces the binding core of the heteroclitic peptide b' to be at the same relative position as the base peptide b, and, implicitly, enforces that the target residue Pt still falls in a non-anchor position within the 9-mer binding core (Step 3). [0566] An updated scoring matrix ^^ଷ ᇱ is computed for heteroclitic peptides conditioned on the potential presentation of the corresponding base peptides by each HLA: ^^ଷ ᇱ ℋ
where each heteroclitic peptide b' ∈ B' is a mutation of base peptide b ∈ B. This condition enforces that if h was not predicted to display b, then all heteroclitic peptides b' derived from b will not be displayed by h (even if h would otherwise be predicted to display b'). [0567] OptiVax-Robust is used to design a final peptide set (e.g., third peptide set) from the union of base peptides and heteroclitic peptides B ∪ B' (with corresponding scoring matrices S2 and ^^ଷ ᇱ for B and B', respectively). OptiVax will output m sets ^^^ for s ∈ [1, …, m] where m is the largest vaccine size requested from OptiVax. Let ^^^ denote the compact set of vaccine peptides output by OptiVax containing k peptides. Note that ^^^ା^ is not necessarily a superset of ^^^. (In alternate embodiments, OptiVax can be used to augment the base set B with peptides from B' using scoring matrix ^^ଶ ᇱ to have OptiVax return set
and the final vaccine set ^^^ା|^| consists of peptides B ∪ ^^^.) [0568] In some embodiments, this procedure is repeated independently for each single target of interest, and the resulting independent vaccine sets can be merged into a combined vaccine as described below. - 105 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 MHC Class I or Class II Vaccine Design Method Prioritizing Peptide Conservation [0569] In some embodiments, peptide sequences that are more conserved across strains, species, or other protein sources of interest are prioritized for vaccine inclusion. In some embodiments, a set of related protein sequences called protein variants are considered for vaccine design. A protein variant is one instance of a family of protein sequences, and protein variants can be sequences from various species, pathogen strains (e.g., viral strains), or other variations considered for vaccine design. In some embodiments, each considered protein variant has an associated probability called a protein variant probability, where the sum of all protein variant probabilities for the supplied set of protein variants is one. In some embodiments, multiple proteins of interest can be considered for the design of a single vaccine using an MHC Class I or Class II vaccine design method prioritizing peptide conservation. In these embodiments, protein variants for all proteins of interest are collectively considered for generating candidate peptides. In some embodiments, the protein variant probabilities across all of the considered multiple proteins sum to one. The methods disclosed herein can be used to design an immunogenic composition, such as a vaccine, based on any protein variant, including variants that have yet to be discovered or future emerging variants (e.g., new virus species or strains). [0570] A set of candidate peptides are created from each protein variant using a sliding window method that parses the protein variant into peptide sequences. In some embodiments, for MHC Class I, 8-mers, 9-mers, 10-mers, and/or 11-mers are produced, but this process can be performed with any desired window lengths and the resulting peptide sets can be combined. In some embodiments, for MHC Class I, only 9-mers are produced. In some embodiments, for MHC Class II, all windowed peptides of length 13–25 are produced, but this process can be performed using any desired window lengths (e.g., only 15-mers). In some embodiments, peptides that are predicted to be glycosylated in a given protein variant are removed and not considered for that variant as described in Liu et al. (2020a), which is incorporated by reference herein in its entirety. [0571] In some embodiments, for each generated peptide sequence (MHC Class I or Class II) conservation is defined as the fraction of input protein variants where the peptide sequence occurs. For example, if a given 9-mer peptide sequence occurs in the peptides generated from 90% of the protein variants provided as input, its conservation is .90. In some embodiments, conservation is defined for each generated peptide sequence (MHC Class I or Class II) as the - 106 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sum of the protein variant frequencies where the peptide sequence occurs. For example, if a given 9-mer peptide sequence occurs in the peptides generated from protein variants with protein variant probabilities of 0.10 and 0.20, its conservation is 0.30. In some embodiments, this functionality is implemented by a COMPUTECONSERVATION function that computes the sum of the frequencies of the protein variants that contain a peptide sequence. In some embodiments, when protein variants are not sufficient for computing expected future conservation, a method of predicting conservation can be used to implement COMPUTECONSERVATION, such as the one disclosed in Hie et al. (2021), which is incorporated by reference herein in its entirety. [0572] In some embodiments, vaccine design considers conservation by prioritizing peptides for vaccine inclusion that are more conserved than others to meet a desired vaccine performance metric. In some embodiments, the vaccine design method attempts to first design a vaccine with candidate peptides that all meet a first conservation threshold, and if the desired vaccine performance is not met, it iteratively adds additional peptides with less stringent conservation to attempt to meet the desired vaccine performance metric. In some embodiments, vaccine design prioritizing conservation proceeds by setting a vaccine design D to be an empty set, and then performing the steps of: (1) selecting candidate peptides in which each peptide passes a conservation threshold to create a candidate peptide set and is not in D, (2) selecting vaccine designs having varying peptide numbers/combinations from this candidate set to optimize a vaccine performance metric using methods disclosed herein for MHC Class I or Class II vaccine design to augment the vaccine design contained in D (one implementation of vaccine augmentation is described in (Liu et al., 2021), incorporated by reference in its entirety herein), (3) selecting the smallest vaccine peptide set design from Step 2 that either meets the desired vaccine performance metric or where adding one more peptide to the selected set does not provide a desired minimum improvement in the vaccine performance metric, (4) if a vaccine peptide set was found in Step 3, adding the vaccine peptide set design from Step 3 to the vaccine design D, and (5) determining whether the vaccine design D meets a desired vaccine performance metric objective, and if so, return vaccine design D as the final vaccine design. If at Step 5, the vaccine design D fails to meet the desired vaccine performance metric objective, the computation continues with the following steps: (6) setting an updated conservation threshold to be lower than the current conservation threshold (less constrained) and (7) repeating the process starting from Step 1, retaining the current vaccine design D and current candidate set, until either a desired vaccine performance metric objective is reached at Step 5, or the updated conservation threshold is lower than a minimum desired conservation threshold at Step - 107 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 6. If on any iteration the updated conservation threshold is lower than a minimum desired conservation threshold, the latest version of vaccine design D will be used as the final vaccine design. When the process completes, the final vaccine design D includes all of the peptides that can be used in a vaccine. [0573] In some embodiments, MHC class I or class II vaccine design procedures consist of the following computational steps. [0574] In some embodiments, the inputs for the computation are: sequence of protein variant j of length nj. ^^^,^ denotes the amino acid at position i of protein variant j, where ^^ ∈ [1, … ^^] and a is the number of protein variants ^^^: Protein variant probability of protein variant ^^^ tj: Position in protein variant ^^^ of the target mutation ^^ ∈ [1, … ^^] D: The vaccine design, initialized to the empty set ∅ s: Substitution mutation ^^ ∈ [ ^^ ^^ ^^ ^^, ^^ ^^ ^^ ^^ ^^] is true if the mutation is a substitution, and false if the mutation is a deletion or insertion or the peptide does not contain a mutation. When the mutation is a deletion or insertion then t indicates the position immediately before the deletion or insertion. ^^^: Initial conservation level of peptides ^^^: Current conservation threshold ^^ଶ: Change in conservation level on each iteration ^^^: Minimum final conservation v: Target vaccine performance metric ^^ௗ: Minimum change in vaccine performance metric to increase vaccine size N: Parameter for EvalVax and OptiVax objective function. Specifies minimum number of predicted per-individual hits for population coverage objective to consider the individual covered. Default = 1 (computes P(n ≥ 1) population coverage). COMPUTECONSERVATION : ^^ × ^^ × ^^ → ℝ: In some embodiments, computes the fraction of sets Xj that contain sequence S. In some embodiments, sums all the Oj where sequence S appears in Xj - 108 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0575] The protein variant sequences ^^^ are used to produce windowed peptides that span the protein sequence(s) starting at each location m with a peptide length of k residues. The result is the set Xj that contains all of the peptide sequences in protein variant Pj. ^^^,^…^ା(^ି^) only produces a sequence when the subscripts are within the range of the defined protein Pj. In some embodiments for MHC Class I, k is chosen to produce 8-mers, 9-mers, 10-mers, and/or 11-mers, but this process can be performed with any desired window lengths and the resulting peptide sets can be combined. In some embodiments for MHC Class I, only 9-mers are produced. In some embodiments for MHC Class II, all windowed peptides of length 13–25 are extracted, but this process can be performed using any desired window lengths (e.g., only 15-mers). , ^^^ ^
[0576] In some embodiments for MHC Class I, the second condition m ≠ {t – (k-1), t – 1} excludes peptides where the mutation at t is in positions P2 or Pk of the windowed k-mer peptide (i.e., the anchor positions) and the mutation is a substitution for MHC Class I design. MHC Class II anchor positions are filtered in the MHC Class II design method. [0577] In some embodiments, the methods disclosed herein are used to create the set of all peptides B that occur in any input protein variant. ^^ = ^ ^^^ ^∈[^,…^] ^^ = | ^^| [0578] In some embodiments, for each peptide ^^௪ in ^^ its conservation metric Cw is computed using COMPUTECONSERVATION Cw = COMPUTECONSERVATION[ ^^௪, X, O] [0579] In some embodiments, the current conservation threshold is then set to the initial conservation threshold: ^^^ = ^^^ - 109 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0580] In some embodiments, at Step 1, candidate peptides are selected where each peptide passes a conservation threshold to create a candidate peptide set and is not already in D. A set of peptide candidates ^^ is defined such that each candidate peptide meets the current conservation threshold c^ and the peptide candidate is not already in D. D is set to be empty (0 peptides) on the first iteration of the computational steps. ^^ = ⋃ ௪∈[^,…,௭] ^^ ௪ ^^ℎ ^^ ^^ ^^ ^^ ௪ ≥ ^^ ^ ^^ ^^ ^^ ^^ ௪ ∉ ^^ [0581] In some embodiments, at Step 2, vaccine designs are selected having varying peptide numbers/combinations from the candidate set to optimize a vaccine performance metric using methods disclosed herein for MHC Class I or Class II vaccine design to augment the vaccine design contained in D. The peptide set ^^ is provided to “MHC Class I Vaccine Design Procedure with Defined Peptide Set ^^” for MHC Class I and “MHC Class II Vaccine Design Procedure with Defined Peptide Set ^^” for MHC Class II. The peptide set ^^ is provided as the set of candidates to augment the set D. Both the set ^^ and D are provided to OptiVax which uses D as the fixed starting set and augments D with peptides from the set ^^ using vaccine augmentation as described in Liu et al., 2021, incorporated by reference in its entirety herein. OptiVax-Robust is used to augment the set D with peptides from ^^ using the scoring matrices as defined in “MHC Class I Vaccine Design Procedure with Defined Peptide Set ^^” for MHC Class I and “MHC Class II Vaccine Design Procedure with Defined Peptide Set ^^” for MHC Class II, and returns sets ^^^ where each set ^^^ is a compact set of vaccine peptides output by OptiVax containing s peptides. In some embodiments, the steps to modify anchor positions are not utilized in the MHC Class I or MHC Class II vaccine design methods and only the base peptides B are utilized for vaccine design. In some embodiments, positions in addition to anchor positions are modified in the MHC Class I or MHC Class II vaccine design methods utilized to create B’. [0582] In some embodiments, at Step 3, the smallest vaccine peptide set design is selected from Step 2 that either meets the desired vaccine performance metric or where adding one more peptide to the selected set does not provide a desired minimum improvement in the vaccine performance metric. A vaccine design ^^^ is chosen that meets minimum requirements. In some embodiments, the vaccine design ^^^ is chosen with the value s chosen to be the minimum value of s such that the difference in vaccine performance between D ∪ ^^^ and D ∪ ^^^ା^ is less than v^. In some embodiments, the value s is chosen to be the minimum value such that the - 110 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 vaccine performance metric of D ∪ meets the final vaccine performance metric v. In some embodiments, ^^^ା^ is not necessarily a superset of ^^^. [0583] In some embodiments, at Step 4, if a vaccine peptide set was found in Step 3, it is added to the vaccine peptide set design D. If an acceptable vaccine design ^^^ was found in Step 4, the vaccine design set D is updated to consist of D ∪ ^^^. [0584] In some embodiments, at Step 5, it is determined whether the vaccine design D meets a desired vaccine performance metric objective. If the vaccine design set D meets the final vaccine performance design metric v, D is returned as the final design. [0585] In some embodiments, at Step 6, the conservation threshold is updated to be lower than the current conservation threshold (less constrained). If the vaccine design set D does not meet the final vaccine performance design metric v, ^^^ is reduced: ^^^ = ^^^ − ^^ଶ [0586] In some embodiments, at Step 7, the process is repeated starting at Step 1, retaining the current vaccine design D and current candidate set, until either a desired vaccine performance metric objective is reached at Step 5, or the updated conservation threshold at Step 6 is lower than a minimum desired conservation threshold. If ^^^< ^^^ then design set D is returned as the final vaccine design. If not, the method returns to Step 1 and repeats all subsequent steps. [0587] In some embodiments, this procedure is repeated independently for each pathogen gene variant or target variant of interest, and the resulting independent vaccine sets can be merged into a combined vaccine. In some embodiments, this procedure is repeated independently for each single protein target of interest (e.g., influenza, cancer neoantigen, etc.), and the resulting independent vaccine sets can be merged into a combined vaccine. Methods for combining multiple vaccines [0588] The above-described methods will produce an optimized target peptide set (e.g., third peptide set) for one or more individual targets. In some embodiments, a method is provided for designing separate vaccines for MHC class I and class II-based immunity for multiple targets (e.g., two or more targets such as KRAS G12D and KRAS G12V). [0589] In some embodiments, a method is disclosed for producing a combined peptide vaccine for multiple targets by using a table of presentations for a disease that is based on - 111 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 empirical data from sources such as the Cancer Genome Atlas (TCGA). In some embodiments, a method is disclosed for producing a combined peptide vaccine for multiple strains of a pathogen (e.g., influenza) that is based on empirical data of strain prevalence where prevalence is used to represent the probability of the presentation of a given strain. In some embodiments, for a given strain presentation, the probabilities of each pathogen protein target are identical and sum to one. In some embodiments, for a given strain presentation, the probabilities of each pathogen protein target vary based on the observed or predicted immunogenicity of each protein (e.g., based on the expression of the pathogen protein or its processing). [0590] FIG.6 shows various embodiment for factoring in disease presentation type (e.g., pancreatic cancer, colorectal cancer, and skin cancer) by probability, for each disease presentation, of target presented for various mutation targets (e.g., KRAS G12D, KRAS G12V, and KRAS G12R). A presentation is a unique set of targets that are presented by one form of a disease (e.g., distinct type of cancer or cancer indication as shown in FIG.6). For each presentation, FIG.6 shows an example of the probability of that presentation, and the probability that a given target is observed. For a given presentation, there can be one or more targets, each having a probability. In some embodiments, the method for multi-target vaccine design will allocate peptide resources for inducing disease immunity based on the presentation and respective target probabilities as shown in FIG.6, for example. In some embodiments, presentations correspond to the prevalence of targets in different human populations or different risk groups. The probability of a target in a population is computed by summing for each possible presentation the probability of that presentation times the probability of the target in that presentation. FIG.6 shows weights used for merging individual vaccines for each target (row) into combined vaccines for each disease indication (column). Values indicate the observed fraction of cases containing each target mutation. Data are from The Cancer Genome Atlas (TCGA). For each disease indication, TCGA data are filtered to cases where the Primary Site is the indication. [0591] In some embodiments, presentations are used to represent different strains of pathogens, where the probability of a presentation is based on the observed prevalence of a given pathogen strain. In some embodiments, for a given strain presentation, the probabilities of each pathogen protein target are identical and sum to one. In some embodiments, for a given strain presentation, the probabilities of each pathogen protein target vary based upon the observed or predicted immunogenicity of each pathogen protein (e.g., based on the expression of - 112 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 the pathogen protein or its processing). In some embodiments, presentation probabilities are used to create a combined vaccine for more than one pathogen strain, where vaccines for each individual strain are combined using the prevalence probabilities of each strain. In some embodiments, the immunogenic importance of each pathogen protein is considered by assigning different presentation probabilities to different pathogen proteins that are used as vaccine targets, and the resulting target specific vaccines are combined using these probabilities. [0592] In some embodiments, the same vaccine design will be generated for mutations to different proteins when the base peptides generated by the mutations to the different proteins are identical. For example, in some embodiments of base peptide selection the following mutations have identical vaccine designs because they share the same set of base peptides: HRAS Q61K, NRAS Q61K, and KRAS Q61K; HRAS Q61L, NRAS Q61L, and KRAS Q61L; HRAS Q61R, NRAS Q61R, and KRAS Q61R. Referring to FIG.6, in some embodiments when two mutations have identical individual vaccine designs their presentation specific probabilities are added when weighting the individual vaccine design for inclusion in a combined vaccine as described below (e.g., for Thyroid Cancer NRAS Q61R and HRAS Q61R). [0593] Referring to FIG.7, in some embodiments, the method first includes designing an individual peptide vaccine for each target to create a combined vaccine design for multiple targets. This initially results in sets of target-specific vaccine designs. In some embodiments, the marginal predicted vaccine performance of each target-specific vaccine at size k is defined by predicted vaccine performance at size k minus the predicted vaccine performance of the vaccine at size k minus one (see FIGs.3-4). The composition of a vaccine may change as the number of peptides used in the vaccine increases, and thus for computing contributions to a combined vaccine the marginal predicted vaccine performance of each target-specific vaccine is used instead of a specific set of peptides. [0594] In some embodiments, the weighted marginal predicted vaccine performance of a target-specific vaccine design for each target specific vaccine size is computed as shown in FIG. 8. For a given target specific vaccine size, its weighted predicted vaccine performance is computed by multiplying its predicted vaccine performance times the probability of the target in the population (e.g., by using values as shown in FIG.6). The marginal weighted predicted vaccine performance for a target specific vaccine is its weighted coverage at size k minus its coverage a size k minus one (e.g., see FIGs.3-4). The marginal weighted predicted vaccine performance of a target specific vaccine of size one is its weighted predicted vaccine - 113 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 performance. The marginal weighted predicted vaccine performances for all vaccines are combined into a single list, and the combined list is sorted from largest to least by the weighted marginal predicted vaccine performances of the target specific vaccines as shown in FIG.7. The combined vaccine of size n is then determined by the first n elements of this list. The peptides for the combined vaccine are determined by the individual peptide target vaccines whose sizes add to n and whose weighted predicted vaccine performances sums to the same sum as the first n elements of the sorted list. This maximizes the predicted vaccine performance of the combined vaccine of size n. [0595] In some embodiments, the combined multiple target vaccine can be designed on its overall predicted coverage for the disease described depending on the presentation table used (e.g., see FIG.6), by its predicted coverage for a specific indication, and/or by its predicted coverage for a specific target by adjusting the weighting used for predicted vaccine performance accordingly. Once a desired level of coverage is selected, the peptides of the combined vaccine are determined by the contributions of target-specific designs. For example, if the combined vaccine includes a target-specific vaccine of size k, then the vaccine peptides for this target at size k are used in the combined vaccine. [0596] Table 1 (below) contains the peptides present in independent (single target) MHC class I vaccine designs. Table 2 (below) contains the contains the peptides present in independent (single target) MHC class II vaccine designs. For alternate embodiments, the Sequence Listing provides heteroclitic peptides useful in MHC class I vaccines and MHC class II vaccines for the mutated proteins, specific protein mutations, and indications in Tables 1 and 2. Any subset of the individual/single target vaccines for MHC class I and class II can be combined to create a vaccine for two or more multiple targets. Combined Vaccine Design Procedure [0597] In some embodiments, the procedure described herein is used to combine individual compact vaccines optimized for different targets into a single optimized combined vaccine. [0598] In some embodiments, the computational inputs for the procedure are: ^^: Set of neoantigen or pathogenic targets of interest (e.g., KRAS G12D, KRAS G12V, KRAS G12R) - 114 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 ^^: Vaccine sets optimized individually for each target. Let ^^௧,^ denote the optimal vaccine set of exactly k peptides for target t ∈ ^^ (e.g., as computed by the procedures describe above). Note that ^^௧,^ା^ may not necessarily be a superset of ^^௧,^. W: ^^ → [0,1] : Target weighting function mapping each target t ∈ ^^ to a probability or weight of t in a particular presentation of interest (e.g., pancreatic cancer; see FIG.6, for example). POPULATIONCOVERAGE: ^^ → [0,1]: Function mapping a peptide set into population coverage (e.g., EvalVax). This function may also take as input additional parameters, including HLA haplotype frequencies and a minimum per-individual number of peptide- HLA hits N (here, we compute coverage as P(n ≥ 1) using EvalVax-Robust). [0599] At Step 1, for each target t (individually) compute optimized vaccines of sizes 1 to m (1 to m peptides; m is the largest vaccine size used for the computation) as the sets ^^௧,^ where k denotes the size of the vaccine. Then, compute the vaccine performance for each vaccine size. For each target t (individually) and vaccine size (peptide count) k, the unweighted population coverage ^^௧,^ is computed: ^^௧,^ = ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^൫ ^^௧,^൯ ∀ ^^ ∈ ^^, ^^ In some embodiments, for each target t, ct,k is generally monotonically increasing and concave down for increasing values of k (each additional peptide increases coverage but with decreasing returns). [0600] At Step 2, vaccine marginal performance is computed and weighted by each target’s prevalence weight. For each target t (individually), the marginal coverage mt,k is computed of the k-th peptide added to the vaccine set: ^^௧,^ if ^^ = 1 ^^ ௧,^ = ^ ^^௧,^ − ^^௧,^ି^, otherwise ∀ ^^ ∈ ^^, ^^ In some embodiments, for each target t, mt,k should be a monotonically decreasing function in k (by Step 1 above). [0601] The weighted marginal population coverage ^^^௧,^ is computed using weights of each target in W:
^^ - 115 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 The weighted marginal population coverage gives the effective marginal coverage of the k-th peptide in the vaccine weighted by the prevalence of the target in the presentation (by multiplication with the probability/weight of the target in the presentation). [0602] At Step 3, the weighted vaccine performances are merged for all targets to produce combined vaccine designs at each peptide count. The individual vaccines are combined into a combined vaccine via the MERGEMULTI procedure called on the weighted marginal population coverage lists ^^^௧ = [ ^^^௧,^, ^^ ∈ 1,2, … ]. FIG.8 shows an example Python implementation of the MERGEMULTI function. This procedure takes as input multiple sorted (descending) lists and merges them into a single sorted (descending) list. Let M indicate the output of MERGEMULTI where each element Mk contains both the marginal weighted coverage and source (target) of the k-th peptide in the combined vaccine. The combined vaccine contains peptides from different targets. In particular, the combined vaccine with k peptides contains
^^ { ^^^ from ^^} peptides from target t. ^^௧,^ ∈ [0, … , ^^] and ∑ ௧ ^^௧,^ = ^^ (Ct,k gives the distribution of the k peptides in the combined vaccine across the targets). [0603] At Step 4, a vaccine with a desired performance is selected. The final vaccine size k can vary based upon the specific population coverage goals of the vaccine. The marginal weighted coverage values of the combined vaccine Mk can be cumulatively summed over k to give the overall effective (target-weighted) population coverage of the combined vaccine containing k peptides as
^^^ (taking into account both the probabilities/weights of the targets in the presentation and the expected population coverage of peptides based on HLA display). [0604] At Step 5, the vaccine peptides corresponding to the target coverage is retrieved for the final vaccine size k. The optimal combined vaccine set ^ ^ ^^ for the final vaccine size k is defined as:
[0605] Thus, the combined vaccine with k peptides is the combination of the optimal individual (Ct,k)-peptide vaccines. The final vaccine size k can vary based upon the specific population coverage goals of the vaccine. - 116 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 MHC class I peptide sequences [0606] In some embodiments, a peptide composition (single target or combined multiple target) comprises about 1 to 40 MHC class I peptides with each peptide consisting of 8 or more amino acids. In some embodiments, an MHC class I peptide composition is intended for one or more of the BRAF, CTNNB1, KRAS, PIK3CA, or TP53 mutated protein targets. In some embodiments, an MHC class I peptide composition is intended for one or more of the BRAF G466V, CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, CTNNB1 T41I, KRAS A146T, KRAS A146V, KRAS Q61H, PIK3CA C420R, PIK3CA E453K, PIK3CA E545A, PIK3CA E726K, PIK3CA G118D, PIK3CA H1047L, PIK3CA N345K, PIK3CA Q546K, PIK3CA Q546R, PIK3CA R108H, TP53 C176F, TP53 C176Y, TP53 C238Y, TP53 C275Y, TP53 E285K, TP53 G245S, TP53 G245V, TP53 H179Y, TP53 H193R, TP53 I195T, TP53 K132E, TP53 K132N, TP53 P151S, TP53 R213L, TP53 R249M, TP53 R249S, TP53 R273L, TP53 R280K, TP53 S127Y, TP53 S241F, TP53 V157F, TP53 V272M, TP53 Y163C, TP53 Y205C, or TP53 Y234C protein mutation targets. In some embodiments, an MHC class I peptide composition is intended to prevent cancer. In some embodiments, an MHC class I peptide composition is intended to treat cancer. [0607] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the BRAF protein comprises one or more of the SEQ ID NOs: 1 to 16 and SEQ ID NO: 795. In some embodiments, any one of the peptides in the BRAF composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16 or SEQ ID NO: 795. [0608] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the BRAF protein comprises one or more of the SEQ ID NOs: 1 to 16, SEQ ID NO: 795, and SEQ ID NOs: 1280 to 2625. In some embodiments, any one of the peptides in the BRAF composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16, SEQ ID NO: 795, or SEQ ID NOs: 1280 to 2625. [0609] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the BRAF protein comprises two or more of the SEQ ID NOs: 1 to 16 and SEQ ID NO: 795. In some embodiments, any one of the peptides in the BRAF - 117 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16 or SEQ ID NO: 795. [0610] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the BRAF protein comprises two or more of the SEQ ID NOs: 1 to 16, SEQ ID NO: 795, and SEQ ID NOs: 1280 to 2625. In some embodiments, any one of the peptides in the BRAF composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16, SEQ ID NO: 795, or SEQ ID NOs: 1280 to 2625. [0611] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the CTNNB1 protein comprises one or more of the SEQ ID NOs: 17 to 184 and SEQ ID NOs: 796 to 801. In some embodiments, any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 184 or SEQ ID NOs: 796 to 801. [0612] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the CTNNB1 protein comprises one or more of the SEQ ID NOs: 17 to 184, SEQ ID NOs: 796 to 801, and SEQ ID NOs: 2626 to 8516. In some embodiments, any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 184, SEQ ID NOs: 796 to 801, or SEQ ID NOs: 2626 to 8516. [0613] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the CTNNB1 protein comprises two or more of the SEQ ID NOs: 17 to 184 and SEQ ID NOs: 796 to 801. In some embodiments, any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 184 or SEQ ID NOs: 796 to 801. [0614] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the CTNNB1 protein comprises two or more of the SEQ ID NOs: 17 to 184, SEQ ID NOs: 796 to 801, and SEQ ID NOs: 2626 to 8516. In some embodiments, any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, - 118 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 184, SEQ ID NOs: 796 to 801, or SEQ ID NOs: 2626 to 8516. [0615] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the KRAS protein comprises one or more of the SEQ ID NOs: 185 to 222 and SEQ ID NOs: 802 to 803. In some embodiments, any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 222 or SEQ ID NOs: 802 to 803. [0616] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the KRAS protein comprises one or more of the SEQ ID NOs: 185 to 222, SEQ ID NOs: 802 to 803, and SEQ ID NOs: 8517 to 10266. In some embodiments, any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 222, SEQ ID NOs: 802 to 803, or SEQ ID NOs: 8517 to 10266. [0617] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the KRAS protein comprises two or more of the SEQ ID NOs: 185 to 222 and SEQ ID NOs: 802 to 803. In some embodiments, any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 222 or SEQ ID NOs: 802 to 803. [0618] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the KRAS protein comprises two or more of the SEQ ID NOs: 185 to 222, SEQ ID NOs: 802 to 803, and SEQ ID NOs: 8517 to 10266. In some embodiments, any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 222, SEQ ID NOs: 802 to 803, or SEQ ID NOs: 8517 to 10266. [0619] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the PIK3CA protein comprises one or more of the SEQ ID NOs: 223 to 386 and SEQ ID NOs: 804 to 813. In some embodiments, any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, - 119 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 386 or SEQ ID NOs: 804 to 813. [0620] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the PIK3CA protein comprises one or more of the SEQ ID NOs: 223 to 386, SEQ ID NOs: 804 to 813, and SEQ ID NOs: 10267 to 15528. In some embodiments, any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 386, SEQ ID NOs: 804 to 813, or SEQ ID NOs: 10267 to 15528. [0621] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the PIK3CA protein comprises two or more of the SEQ ID NOs: 223 to 386 and SEQ ID NOs: 804 to 813. In some embodiments, any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 386 or SEQ ID NOs: 804 to 813. [0622] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the PIK3CA protein comprises two or more of the SEQ ID NOs: 223 to 386, SEQ ID NOs: 804 to 813, and SEQ ID NOs: 10267 to 15528. In some embodiments, any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 386, SEQ ID NOs: 804 to 813, or SEQ ID NOs: 10267 to 15528. [0623] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the TP53 protein comprises one or more of the SEQ ID NOs: 387 to 794 and SEQ ID NOs: 814 to 834. In some embodiments, any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 794 or SEQ ID NOs: 814 to 834. [0624] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the TP53 protein comprises one or more of the SEQ ID NOs: 387 to 794, SEQ ID NOs: 814 to 834, and SEQ ID NOs: 15529 to 36796. In some embodiments, any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, - 120 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 794, SEQ ID NOs: 814 to 834, or SEQ ID NOs: 15529 to 36796. [0625] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the TP53 protein comprises two or more of the SEQ ID NOs: 387 to 794 and SEQ ID NOs: 814 to 834. In some embodiments, any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 794 or SEQ ID NOs: 814 to 834. [0626] In some embodiments, the amino acid sequence for a MHC class I peptide composition for mutation in the TP53 protein comprises two or more of the SEQ ID NOs: 387 to 794, SEQ ID NOs: 814 to 834, and SEQ ID NOs: 15529 to 36796. In some embodiments, any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 794, SEQ ID NOs: 814 to 834, or SEQ ID NOs: 15529 to 36796. [0627] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the BRAF G466V protein mutation comprises one or more of the SEQ ID NOs: 1 to 16 and SEQ ID NO: 795. In some embodiments, any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16 or SEQ ID NO: 795. [0628] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the BRAF G466V protein mutation comprises one or more of the SEQ ID NOs: 1 to 16, SEQ ID NO: 795, and SEQ ID NOs: 1280 to 2625. In some embodiments, any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16, SEQ ID NO: 795, or SEQ ID NOs: 1280 to 2625. [0629] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the BRAF G466V protein mutation comprises two or more of the SEQ ID NOs: 1 to 16 and SEQ ID NO: 795. In some embodiments, any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16 or SEQ ID NO: 795. [0630] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the BRAF G466V protein mutation comprises two or more of the SEQ ID NOs: - 121 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 1 to 16, SEQ ID NO: 795, and SEQ ID NOs: 1280 to 2625. In some embodiments, any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16, SEQ ID NO: 795, or SEQ ID NOs: 1280 to 2625. [0631] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 D32G protein mutation comprises one or more of the SEQ ID NOs: 17 to 36. In some embodiments, any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 36. [0632] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 D32G protein mutation comprises one or more of the SEQ ID NOs: 17 to 36 and SEQ ID NOs: 2626 to 3063. In some embodiments, any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 36 or SEQ ID NOs: 2626 to 3063. [0633] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 D32G protein mutation comprises two or more of the SEQ ID NOs: 17 to 36. In some embodiments, any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 36. [0634] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 D32G protein mutation comprises two or more of the SEQ ID NOs: 17 to 36 and SEQ ID NOs: 2626 to 3063. In some embodiments, any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 36 or SEQ ID NOs: 2626 to 3063. [0635] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 G34E protein mutation comprises one or more of the SEQ ID NOs: 37 to 52. In some embodiments, any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 37 to 52. - 122 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0636] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 G34E protein mutation comprises one or more of the SEQ ID NOs: 37 to 52 and SEQ ID NOs: 3064 to 3582. In some embodiments, any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 37 to 52 or SEQ ID NOs: 3064 to 3582. [0637] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 G34E protein mutation comprises two or more of the SEQ ID NOs: 37 to 52. In some embodiments, any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 37 to 52. [0638] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 G34E protein mutation comprises two or more of the SEQ ID NOs: 37 to 52 and SEQ ID NOs: 3064 to 3582. In some embodiments, any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 37 to 52 or SEQ ID NOs: 3064 to 3582. [0639] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33C protein mutation comprises one or more of the SEQ ID NOs: 53 to 67. In some embodiments, any one of the peptides in the CTNNB1 S33C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 53 to 67. [0640] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33C protein mutation comprises one or more of the SEQ ID NOs: 53 to 67 and SEQ ID NOs: 3583 to 3914. In some embodiments, any one of the peptides in the CTNNB1 S33C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 53 to 67 or SEQ ID NOs: 3583 to 3914. [0641] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33C protein mutation comprises two or more of the SEQ ID NOs: 53 to 67. In some embodiments, any one of the peptides in the CTNNB1 S33C - 123 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 53 to 67. [0642] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33C protein mutation comprises two or more of the SEQ ID NOs: 53 to 67 and SEQ ID NOs: 3583 to 3914. In some embodiments, any one of the peptides in the CTNNB1 S33C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 53 to 67 or SEQ ID NOs: 3583 to 3914. [0643] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33F protein mutation comprises one or more of the SEQ ID NOs: 68 to 86. In some embodiments, any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 68 to 86. [0644] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33F protein mutation comprises one or more of the SEQ ID NOs: 68 to 86 and SEQ ID NOs: 3915 to 4542. In some embodiments, any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 68 to 86 or SEQ ID NOs: 3915 to 4542. [0645] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33F protein mutation comprises two or more of the SEQ ID NOs: 68 to 86. In some embodiments, any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 68 to 86. [0646] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S33F protein mutation comprises two or more of the SEQ ID NOs: 68 to 86 and SEQ ID NOs: 3915 to 4542. In some embodiments, any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 68 to 86 or SEQ ID NOs: 3915 to 4542. - 124 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0647] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37C protein mutation comprises one or more of the SEQ ID NOs: 87 to 102 and SEQ ID NO: 796. In some embodiments, any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 87 to 102 or SEQ ID NO: 796. [0648] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37C protein mutation comprises one or more of the SEQ ID NOs: 87 to 102, SEQ ID NO: 796, and SEQ ID NOs: 4543 to 5000. In some embodiments, any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 87 to 102, SEQ ID NO: 796, or SEQ ID NOs: 4543 to 5000. [0649] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37C protein mutation comprises two or more of the SEQ ID NOs: 87 to 102 and SEQ ID NO: 796. In some embodiments, any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 87 to 102 or SEQ ID NO: 796. [0650] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37C protein mutation comprises two or more of the SEQ ID NOs: 87 to 102, SEQ ID NO: 796, and SEQ ID NOs: 4543 to 5000. In some embodiments, any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 87 to 102, SEQ ID NO: 796, or SEQ ID NOs: 4543 to 5000. [0651] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37F protein mutation comprises one or more of the SEQ ID NOs: 103 to 119. In some embodiments, any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 103 to 119. [0652] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37F protein mutation comprises one or more of the SEQ ID - 125 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 NOs: 103 to 119 and SEQ ID NOs: 5001 to 5916. In some embodiments, any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 103 to 119 or SEQ ID NOs: 5001 to 5916. [0653] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37F protein mutation comprises two or more of the SEQ ID NOs: 103 to 119. In some embodiments, any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 103 to 119. [0654] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S37F protein mutation comprises two or more of the SEQ ID NOs: 103 to 119 and SEQ ID NOs: 5001 to 5916. In some embodiments, any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 103 to 119 or SEQ ID NOs: 5001 to 5916. [0655] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45F protein mutation comprises one or more of the SEQ ID NOs: 120 to 134 and SEQ ID NO: 797. In some embodiments, any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 120 to 134 or SEQ ID NO: 797. [0656] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45F protein mutation comprises one or more of the SEQ ID NOs: 120 to 134, SEQ ID NO: 797, and SEQ ID NOs: 5917 to 6394. In some embodiments, any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 120 to 134, SEQ ID NO: 797, or SEQ ID NOs: 5917 to 6394. [0657] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45F protein mutation comprises two or more of the SEQ ID NOs: 120 to 134 and SEQ ID NO: 797. In some embodiments, any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, - 126 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 120 to 134 or SEQ ID NO: 797. [0658] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45F protein mutation comprises two or more of the SEQ ID NOs: 120 to 134, SEQ ID NO: 797, and SEQ ID NOs: 5917 to 6394. In some embodiments, any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 120 to 134, SEQ ID NO: 797, or SEQ ID NOs: 5917 to 6394. [0659] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45P protein mutation comprises one or more of the SEQ ID NOs: 135 to 150 and SEQ ID NO: 798. In some embodiments, any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 135 to 150 or SEQ ID NO: 798. [0660] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45P protein mutation comprises one or more of the SEQ ID NOs: 135 to 150, SEQ ID NO: 798, and SEQ ID NOs: 6395 to 7051. In some embodiments, any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 135 to 150, SEQ ID NO: 798, or SEQ ID NOs: 6395 to 7051. [0661] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45P protein mutation comprises two or more of the SEQ ID NOs: 135 to 150 and SEQ ID NO: 798. In some embodiments, any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 135 to 150 or SEQ ID NO: 798. [0662] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 S45P protein mutation comprises two or more of the SEQ ID NOs: 135 to 150, SEQ ID NO: 798, and SEQ ID NOs: 6395 to 7051. In some embodiments, any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, - 127 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 135 to 150, SEQ ID NO: 798, or SEQ ID NOs: 6395 to 7051. [0663] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41A protein mutation comprises one or more of the SEQ ID NOs: 151 to 167 and SEQ ID NOs: 799 to 800. In some embodiments, any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 151 to 167 or SEQ ID NOs: 799 to 800. [0664] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41A protein mutation comprises one or more of the SEQ ID NOs: 151 to 167, SEQ ID NOs: 799 to 800, and SEQ ID NOs: 7052 to 7846. In some embodiments, any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 151 to 167, SEQ ID NOs: 799 to 800, or SEQ ID NOs: 7052 to 7846. [0665] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41A protein mutation comprises two or more of the SEQ ID NOs: 151 to 167 and SEQ ID NOs: 799 to 800. In some embodiments, any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 151 to 167 or SEQ ID NOs: 799 to 800. [0666] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41A protein mutation comprises two or more of the SEQ ID NOs: 151 to 167, SEQ ID NOs: 799 to 800, and SEQ ID NOs: 7052 to 7846. In some embodiments, any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 151 to 167, SEQ ID NOs: 799 to 800, or SEQ ID NOs: 7052 to 7846. [0667] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41I protein mutation comprises one or more of the SEQ ID NOs: 168 to 184 and SEQ ID NO: 801. In some embodiments, any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, - 128 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 168 to 184 or SEQ ID NO: 801. [0668] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41I protein mutation comprises one or more of the SEQ ID NOs: 168 to 184, SEQ ID NO: 801, and SEQ ID NOs: 7847 to 8516. In some embodiments, any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 168 to 184, SEQ ID NO: 801, or SEQ ID NOs: 7847 to 8516. [0669] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41I protein mutation comprises two or more of the SEQ ID NOs: 168 to 184 and SEQ ID NO: 801. In some embodiments, any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 168 to 184 or SEQ ID NO: 801. [0670] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the CTNNB1 T41I protein mutation comprises two or more of the SEQ ID NOs: 168 to 184, SEQ ID NO: 801, and SEQ ID NOs: 7847 to 8516. In some embodiments, any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 168 to 184, SEQ ID NO: 801, or SEQ ID NOs: 7847 to 8516. [0671] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS A146T protein mutation comprises one or more of the SEQ ID NOs: 185 to 193 and SEQ ID NO: 802. In some embodiments, any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 193 or SEQ ID NO: 802. [0672] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS A146T protein mutation comprises one or more of the SEQ ID NOs: 185 to 193, SEQ ID NO: 802, and SEQ ID NOs: 8517 to 8904. In some embodiments, any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 193, SEQ ID NO: 802, or SEQ ID NOs: 8517 to 8904. - 129 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0673] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS A146T protein mutation comprises two or more of the SEQ ID NOs: 185 to 193 and SEQ ID NO: 802. In some embodiments, any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 193 or SEQ ID NO: 802. [0674] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS A146T protein mutation comprises two or more of the SEQ ID NOs: 185 to 193, SEQ ID NO: 802, and SEQ ID NOs: 8517 to 8904. In some embodiments, any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 193, SEQ ID NO: 802, or SEQ ID NOs: 8517 to 8904. [0675] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS A146V protein mutation comprises one or more of the SEQ ID NOs: 194 to 202 and SEQ ID NO: 803. In some embodiments, any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 194 to 202 or SEQ ID NO: 803. [0676] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS A146V protein mutation comprises one or more of the SEQ ID NOs: 194 to 202, SEQ ID NO: 803, and SEQ ID NOs: 8905 to 9308. In some embodiments, any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 194 to 202, SEQ ID NO: 803, or SEQ ID NOs: 8905 to 9308. [0677] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS A146V protein mutation comprises two or more of the SEQ ID NOs: 194 to 202 and SEQ ID NO: 803. In some embodiments, any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 194 to 202 or SEQ ID NO: 803. [0678] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS A146V protein mutation comprises two or more of the SEQ ID NOs: 194 to 202, SEQ ID NO: 803, and SEQ ID NOs: 8905 to 9308. In some embodiments, any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, - 130 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 194 to 202, SEQ ID NO: 803, or SEQ ID NOs: 8905 to 9308. [0679] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS Q61H protein mutation comprises one or more of the SEQ ID NOs: 203 to 222. In some embodiments, any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 203 to 222. [0680] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS Q61H protein mutation comprises one or more of the SEQ ID NOs: 203 to 222 and SEQ ID NOs: 9309 to 10266. In some embodiments, any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 203 to 222 or SEQ ID NOs: 9309 to 10266. [0681] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS Q61H protein mutation comprises two or more of the SEQ ID NOs: 203 to 222. In some embodiments, any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 203 to 222. [0682] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the KRAS Q61H protein mutation comprises two or more of the SEQ ID NOs: 203 to 222 and SEQ ID NOs: 9309 to 10266. In some embodiments, any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 203 to 222 or SEQ ID NOs: 9309 to 10266. [0683] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA C420R protein mutation comprises one or more of the SEQ ID NOs: 223 to 239 and SEQ ID NOs: 804 to 805. In some embodiments, any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 239 or SEQ ID NOs: 804 to 805. - 131 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0684] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA C420R protein mutation comprises one or more of the SEQ ID NOs: 223 to 239, SEQ ID NOs: 804 to 805, and SEQ ID NOs: 10267 to 10781. In some embodiments, any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 239, SEQ ID NOs: 804 to 805, or SEQ ID NOs: 10267 to 10781. [0685] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA C420R protein mutation comprises two or more of the SEQ ID NOs: 223 to 239 and SEQ ID NOs: 804 to 805. In some embodiments, any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 239 or SEQ ID NOs: 804 to 805. [0686] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA C420R protein mutation comprises two or more of the SEQ ID NOs: 223 to 239, SEQ ID NOs: 804 to 805, and SEQ ID NOs: 10267 to 10781. In some embodiments, any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 239, SEQ ID NOs: 804 to 805, or SEQ ID NOs: 10267 to 10781. [0687] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E453K protein mutation comprises one or more of the SEQ ID NOs: 240 to 255 and SEQ ID NOs: 806 to 807. In some embodiments, any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 240 to 255 or SEQ ID NOs: 806 to 807. [0688] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E453K protein mutation comprises one or more of the SEQ ID NOs: 240 to 255, SEQ ID NOs: 806 to 807, and SEQ ID NOs: 10782 to 11260. In some embodiments, any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 132 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 identical to SEQ ID NOs: 240 to 255, SEQ ID NOs: 806 to 807, or SEQ ID NOs: 10782 to 11260. [0689] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E453K protein mutation comprises two or more of the SEQ ID NOs: 240 to 255 and SEQ ID NOs: 806 to 807. In some embodiments, any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 240 to 255 or SEQ ID NOs: 806 to 807. [0690] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E453K protein mutation comprises two or more of the SEQ ID NOs: 240 to 255, SEQ ID NOs: 806 to 807, and SEQ ID NOs: 10782 to 11260. In some embodiments, any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 240 to 255, SEQ ID NOs: 806 to 807, or SEQ ID NOs: 10782 to 11260. [0691] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E545A protein mutation comprises one or more of the SEQ ID NOs: 256 to 271 and SEQ ID NO: 808. In some embodiments, any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 256 to 271 or SEQ ID NO: 808. [0692] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E545A protein mutation comprises one or more of the SEQ ID NOs: 256 to 271, SEQ ID NO: 808, and SEQ ID NOs: 11261 to 11604. In some embodiments, any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 256 to 271, SEQ ID NO: 808, or SEQ ID NOs: 11261 to 11604. [0693] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E545A protein mutation comprises two or more of the SEQ ID NOs: 256 to 271 and SEQ ID NO: 808. In some embodiments, any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, - 133 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 256 to 271 or SEQ ID NO: 808. [0694] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E545A protein mutation comprises two or more of the SEQ ID NOs: 256 to 271, SEQ ID NO: 808, and SEQ ID NOs: 11261 to 11604. In some embodiments, any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 256 to 271, SEQ ID NO: 808, or SEQ ID NOs: 11261 to 11604. [0695] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E726K protein mutation comprises one or more of the SEQ ID NOs: 272 to 290 and SEQ ID NO: 809. In some embodiments, any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 272 to 290 or SEQ ID NO: 809. [0696] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E726K protein mutation comprises one or more of the SEQ ID NOs: 272 to 290, SEQ ID NO: 809, and SEQ ID NOs: 11605 to 12160. In some embodiments, any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 272 to 290, SEQ ID NO: 809, or SEQ ID NOs: 11605 to 12160. [0697] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E726K protein mutation comprises two or more of the SEQ ID NOs: 272 to 290 and SEQ ID NO: 809. In some embodiments, any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 272 to 290 or SEQ ID NO: 809. [0698] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA E726K protein mutation comprises two or more of the SEQ ID NOs: 272 to 290, SEQ ID NO: 809, and SEQ ID NOs: 11605 to 12160. In some embodiments, any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence - 134 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 272 to 290, SEQ ID NO: 809, or SEQ ID NOs: 11605 to 12160. [0699] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA G118D protein mutation comprises one or more of the SEQ ID NOs: 291 to 307. In some embodiments, any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 291 to 307. [0700] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA G118D protein mutation comprises one or more of the SEQ ID NOs: 291 to 307 and SEQ ID NOs: 12161 to 12944. In some embodiments, any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 291 to 307 or SEQ ID NOs: 12161 to 12944. [0701] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA G118D protein mutation comprises two or more of the SEQ ID NOs: 291 to 307. In some embodiments, any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 291 to 307. [0702] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA G118D protein mutation comprises two or more of the SEQ ID NOs: 291 to 307 and SEQ ID NOs: 12161 to 12944. In some embodiments, any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 291 to 307 or SEQ ID NOs: 12161 to 12944. [0703] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA H1047L protein mutation comprises one or more of the SEQ ID NOs: 308 to 325. In some embodiments, any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 308 to 325. [0704] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA H1047L protein mutation comprises one or more of the SEQ ID - 135 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 NOs: 308 to 325 and SEQ ID NOs: 12945 to 13568. In some embodiments, any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 308 to 325 or SEQ ID NOs: 12945 to 13568. [0705] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA H1047L protein mutation comprises two or more of the SEQ ID NOs: 308 to 325. In some embodiments, any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 308 to 325. [0706] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA H1047L protein mutation comprises two or more of the SEQ ID NOs: 308 to 325 and SEQ ID NOs: 12945 to 13568. In some embodiments, any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 308 to 325 or SEQ ID NOs: 12945 to 13568. [0707] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA N345K protein mutation comprises one or more of the SEQ ID NOs: 326 to 339 and SEQ ID NOs: 810 to 811. In some embodiments, any one of the peptides in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 326 to 339 or SEQ ID NOs: 810 to 811. [0708] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA N345K protein mutation comprises one or more of the SEQ ID NOs: 326 to 339, SEQ ID NOs: 810 to 811, and SEQ ID NOs: 13569 to 13997. In some embodiments, any one of the peptides in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 326 to 339, SEQ ID NOs: 810 to 811, or SEQ ID NOs: 13569 to 13997. [0709] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA N345K protein mutation comprises two or more of the SEQ ID NOs: 326 to 339 and SEQ ID NOs: 810 to 811. In some embodiments, any one of the peptides - 136 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 326 to 339 or SEQ ID NOs: 810 to 811. [0710] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA N345K protein mutation comprises two or more of the SEQ ID NOs: 326 to 339, SEQ ID NOs: 810 to 811, and SEQ ID NOs: 13569 to 13997. In some embodiments, any one of the peptides in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 326 to 339, SEQ ID NOs: 810 to 811, or SEQ ID NOs: 13569 to 13997. [0711] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546K protein mutation comprises one or more of the SEQ ID NOs: 340 to 358 and SEQ ID NO: 812. In some embodiments, any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 340 to 358 or SEQ ID NO: 812. [0712] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546K protein mutation comprises one or more of the SEQ ID NOs: 340 to 358, SEQ ID NO: 812, and SEQ ID NOs: 13998 to 14491. In some embodiments, any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 340 to 358, SEQ ID NO: 812, or SEQ ID NOs: 13998 to 14491. [0713] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546K protein mutation comprises two or more of the SEQ ID NOs: 340 to 358 and SEQ ID NO: 812. In some embodiments, any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 340 to 358 or SEQ ID NO: 812. [0714] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546K protein mutation comprises two or more of the SEQ ID NOs: 340 to 358, SEQ ID NO: 812, and SEQ ID NOs: 13998 to 14491. In some embodiments, - 137 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 340 to 358, SEQ ID NO: 812, or SEQ ID NOs: 13998 to 14491. [0715] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546R protein mutation comprises one or more of the SEQ ID NOs: 359 to 376 and SEQ ID NO: 813. In some embodiments, any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 359 to 376 or SEQ ID NO: 813. [0716] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546R protein mutation comprises one or more of the SEQ ID NOs: 359 to 376, SEQ ID NO: 813, and SEQ ID NOs: 14492 to 15002. In some embodiments, any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 359 to 376, SEQ ID NO: 813, or SEQ ID NOs: 14492 to 15002. [0717] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546R protein mutation comprises two or more of the SEQ ID NOs: 359 to 376 and SEQ ID NO: 813. In some embodiments, any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 359 to 376 or SEQ ID NO: 813. [0718] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA Q546R protein mutation comprises two or more of the SEQ ID NOs: 359 to 376, SEQ ID NO: 813, and SEQ ID NOs: 14492 to 15002. In some embodiments, any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 359 to 376, SEQ ID NO: 813, or SEQ ID NOs: 14492 to 15002. [0719] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA R108H protein mutation comprises one or more of the SEQ ID NOs: 377 to 386. In some embodiments, any one of the peptides in the PIK3CA R108H - 138 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 377 to 386. [0720] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA R108H protein mutation comprises one or more of the SEQ ID NOs: 377 to 386 and SEQ ID NOs: 15003 to 15528. In some embodiments, any one of the peptides in the PIK3CA R108H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 377 to 386 or SEQ ID NOs: 15003 to 15528. [0721] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA R108H protein mutation comprises two or more of the SEQ ID NOs: 377 to 386. In some embodiments, any one of the peptides in the PIK3CA R108H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 377 to 386. [0722] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the PIK3CA R108H protein mutation comprises two or more of the SEQ ID NOs: 377 to 386 and SEQ ID NOs: 15003 to 15528. In some embodiments, any one of the peptides in the PIK3CA R108H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 377 to 386 or SEQ ID NOs: 15003 to 15528. [0723] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C176F protein mutation comprises one or more of the SEQ ID NOs: 387 to 403 and SEQ ID NOs: 814 to 815. In some embodiments, any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 403 or SEQ ID NOs: 814 to 815. [0724] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C176F protein mutation comprises one or more of the SEQ ID NOs: 387 to 403, SEQ ID NOs: 814 to 815, and SEQ ID NOs: 15529 to 16093. In some embodiments, any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 139 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 identical to SEQ ID NOs: 387 to 403, SEQ ID NOs: 814 to 815, or SEQ ID NOs: 15529 to 16093. [0725] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C176F protein mutation comprises two or more of the SEQ ID NOs: 387 to 403 and SEQ ID NOs: 814 to 815. In some embodiments, any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 403 or SEQ ID NOs: 814 to 815. [0726] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C176F protein mutation comprises two or more of the SEQ ID NOs: 387 to 403, SEQ ID NOs: 814 to 815, and SEQ ID NOs: 15529 to 16093. In some embodiments, any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 403, SEQ ID NOs: 814 to 815, or SEQ ID NOs: 15529 to 16093. [0727] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C176Y protein mutation comprises one or more of the SEQ ID NOs: 404 to 420 and SEQ ID NO: 816. In some embodiments, any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 404 to 420 or SEQ ID NO: 816. [0728] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C176Y protein mutation comprises one or more of the SEQ ID NOs: 404 to 420, SEQ ID NO: 816, and SEQ ID NOs: 16094 to 16634. In some embodiments, any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 404 to 420, SEQ ID NO: 816, or SEQ ID NOs: 16094 to 16634. [0729] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C176Y protein mutation comprises two or more of the SEQ ID NOs: 404 to 420 and SEQ ID NO: 816. In some embodiments, any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 404 to 420 or SEQ ID NO: 816. - 140 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0730] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C176Y protein mutation comprises two or more of the SEQ ID NOs: 404 to 420, SEQ ID NO: 816, and SEQ ID NOs: 16094 to 16634. In some embodiments, any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 404 to 420, SEQ ID NO: 816, or SEQ ID NOs: 16094 to 16634. [0731] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C238Y protein mutation comprises one or more of the SEQ ID NOs: 421 to 440. In some embodiments, any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 421 to 440. [0732] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C238Y protein mutation comprises one or more of the SEQ ID NOs: 421 to 440 and SEQ ID NOs: 16635 to 17413. In some embodiments, any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 421 to 440 or SEQ ID NOs: 16635 to 17413. [0733] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C238Y protein mutation comprises two or more of the SEQ ID NOs: 421 to 440. In some embodiments, any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 421 to 440. [0734] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C238Y protein mutation comprises two or more of the SEQ ID NOs: 421 to 440 and SEQ ID NOs: 16635 to 17413. In some embodiments, any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 421 to 440 or SEQ ID NOs: 16635 to 17413. [0735] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C275Y protein mutation comprises one or more of the SEQ ID NOs: 441 to 457. In some embodiments, any one of the peptides in the TP53 C275Y composition - 141 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 441 to 457. [0736] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C275Y protein mutation comprises one or more of the SEQ ID NOs: 441 to 457 and SEQ ID NOs: 17414 to 18100. In some embodiments, any one of the peptides in the TP53 C275Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 441 to 457 or SEQ ID NOs: 17414 to 18100. [0737] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C275Y protein mutation comprises two or more of the SEQ ID NOs: 441 to 457. In some embodiments, any one of the peptides in the TP53 C275Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 441 to 457. [0738] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 C275Y protein mutation comprises two or more of the SEQ ID NOs: 441 to 457 and SEQ ID NOs: 17414 to 18100. In some embodiments, any one of the peptides in the TP53 C275Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 441 to 457 or SEQ ID NOs: 17414 to 18100. [0739] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 E285K protein mutation comprises one or more of the SEQ ID NOs: 458 to 473 and SEQ ID NOs: 817 to 818. In some embodiments, any one of the peptides in the TP53 E285K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 458 to 473 or SEQ ID NOs: 817 to 818. [0740] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 E285K protein mutation comprises one or more of the SEQ ID NOs: 458 to 473, SEQ ID NOs: 817 to 818, and SEQ ID NOs: 18101 to 18739. In some embodiments, any one of the peptides in the TP53 E285K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 142 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 identical to SEQ ID NOs: 458 to 473, SEQ ID NOs: 817 to 818, or SEQ ID NOs: 18101 to 18739. [0741] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 E285K protein mutation comprises two or more of the SEQ ID NOs: 458 to 473 and SEQ ID NOs: 817 to 818. In some embodiments, any one of the peptides in the TP53 E285K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 458 to 473 or SEQ ID NOs: 817 to 818. [0742] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 E285K protein mutation comprises two or more of the SEQ ID NOs: 458 to 473, SEQ ID NOs: 817 to 818, and SEQ ID NOs: 18101 to 18739. In some embodiments, any one of the peptides in the TP53 E285K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 458 to 473, SEQ ID NOs: 817 to 818, or SEQ ID NOs: 18101 to 18739. [0743] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 G245S protein mutation comprises one or more of the SEQ ID NOs: 474 to 492. In some embodiments, any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 474 to 492. [0744] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 G245S protein mutation comprises one or more of the SEQ ID NOs: 474 to 492 and SEQ ID NOs: 18740 to 19567. In some embodiments, any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 474 to 492 or SEQ ID NOs: 18740 to 19567. [0745] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 G245S protein mutation comprises two or more of the SEQ ID NOs: 474 to 492. In some embodiments, any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 474 to 492. - 143 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0746] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 G245S protein mutation comprises two or more of the SEQ ID NOs: 474 to 492 and SEQ ID NOs: 18740 to 19567. In some embodiments, any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 474 to 492 or SEQ ID NOs: 18740 to 19567. [0747] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 G245V protein mutation comprises one or more of the SEQ ID NOs: 493 to 511. In some embodiments, any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 493 to 511. [0748] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 G245V protein mutation comprises one or more of the SEQ ID NOs: 493 to 511 and SEQ ID NOs: 19568 to 20400. In some embodiments, any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 493 to 511 or SEQ ID NOs: 19568 to 20400. [0749] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 G245V protein mutation comprises two or more of the SEQ ID NOs: 493 to 511. In some embodiments, any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 493 to 511. [0750] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 G245V protein mutation comprises two or more of the SEQ ID NOs: 493 to 511 and SEQ ID NOs: 19568 to 20400. In some embodiments, any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 493 to 511 or SEQ ID NOs: 19568 to 20400. [0751] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 H179Y protein mutation comprises one or more of the SEQ ID NOs: 512 to 529 and SEQ ID NOs: 819 to 820. In some embodiments, any one of the peptides in the - 144 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 512 to 529 or SEQ ID NOs: 819 to 820. [0752] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 H179Y protein mutation comprises one or more of the SEQ ID NOs: 512 to 529, SEQ ID NOs: 819 to 820, and SEQ ID NOs: 20401 to 20880. In some embodiments, any one of the peptides in the TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 512 to 529, SEQ ID NOs: 819 to 820, or SEQ ID NOs: 20401 to 20880. [0753] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 H179Y protein mutation comprises two or more of the SEQ ID NOs: 512 to 529 and SEQ ID NOs: 819 to 820. In some embodiments, any one of the peptides in the TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 512 to 529 or SEQ ID NOs: 819 to 820. [0754] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 H179Y protein mutation comprises two or more of the SEQ ID NOs: 512 to 529, SEQ ID NOs: 819 to 820, and SEQ ID NOs: 20401 to 20880. In some embodiments, any one of the peptides in the TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 512 to 529, SEQ ID NOs: 819 to 820, or SEQ ID NOs: 20401 to 20880. [0755] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 H193R protein mutation comprises one or more of the SEQ ID NOs: 530 to 546. In some embodiments, any one of the peptides in the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 530 to 546. [0756] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 H193R protein mutation comprises one or more of the SEQ ID NOs: 530 to 546 and SEQ ID NOs: 20881 to 21921. In some embodiments, any one of the peptides in - 145 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 530 to 546 or SEQ ID NOs: 20881 to 21921. [0757] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 H193R protein mutation comprises two or more of the SEQ ID NOs: 530 to 546. In some embodiments, any one of the peptides in the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 530 to 546. [0758] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 H193R protein mutation comprises two or more of the SEQ ID NOs: 530 to 546 and SEQ ID NOs: 20881 to 21921. In some embodiments, any one of the peptides in the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 530 to 546 or SEQ ID NOs: 20881 to 21921. [0759] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 I195T protein mutation comprises one or more of the SEQ ID NOs: 547 to 563 and SEQ ID NO: 821. In some embodiments, any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 547 to 563 or SEQ ID NO: 821. [0760] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 I195T protein mutation comprises one or more of the SEQ ID NOs: 547 to 563, SEQ ID NO: 821, and SEQ ID NOs: 21922 to 22738. In some embodiments, any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 547 to 563, SEQ ID NO: 821, or SEQ ID NOs: 21922 to 22738. [0761] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 I195T protein mutation comprises two or more of the SEQ ID NOs: 547 to 563 and SEQ ID NO: 821. In some embodiments, any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 547 to 563 or SEQ ID NO: 821. - 146 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0762] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 I195T protein mutation comprises two or more of the SEQ ID NOs: 547 to 563, SEQ ID NO: 821, and SEQ ID NOs: 21922 to 22738. In some embodiments, any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 547 to 563, SEQ ID NO: 821, or SEQ ID NOs: 21922 to 22738. [0763] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 K132E protein mutation comprises one or more of the SEQ ID NOs: 564 to 582 and SEQ ID NO: 822. In some embodiments, any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 564 to 582 or SEQ ID NO: 822. [0764] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 K132E protein mutation comprises one or more of the SEQ ID NOs: 564 to 582, SEQ ID NO: 822, and SEQ ID NOs: 22739 to 24317. In some embodiments, any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 564 to 582, SEQ ID NO: 822, or SEQ ID NOs: 22739 to 24317. [0765] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 K132E protein mutation comprises two or more of the SEQ ID NOs: 564 to 582 and SEQ ID NO: 822. In some embodiments, any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 564 to 582 or SEQ ID NO: 822. [0766] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 K132E protein mutation comprises two or more of the SEQ ID NOs: 564 to 582, SEQ ID NO: 822, and SEQ ID NOs: 22739 to 24317. In some embodiments, any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 564 to 582, SEQ ID NO: 822, or SEQ ID NOs: 22739 to 24317. [0767] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 K132N protein mutation comprises one or more of the SEQ ID NOs: 583 to 599 and SEQ ID NOs: 823 to 824. In some embodiments, any one of the peptides in the - 147 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 583 to 599 or SEQ ID NOs: 823 to 824. [0768] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 K132N protein mutation comprises one or more of the SEQ ID NOs: 583 to 599, SEQ ID NOs: 823 to 824, and SEQ ID NOs: 24318 to 25729. In some embodiments, any one of the peptides in the TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 583 to 599, SEQ ID NOs: 823 to 824, or SEQ ID NOs: 24318 to 25729. [0769] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 K132N protein mutation comprises two or more of the SEQ ID NOs: 583 to 599 and SEQ ID NOs: 823 to 824. In some embodiments, any one of the peptides in the TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 583 to 599 or SEQ ID NOs: 823 to 824. [0770] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 K132N protein mutation comprises two or more of the SEQ ID NOs: 583 to 599, SEQ ID NOs: 823 to 824, and SEQ ID NOs: 24318 to 25729. In some embodiments, any one of the peptides in the TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 583 to 599, SEQ ID NOs: 823 to 824, or SEQ ID NOs: 24318 to 25729. [0771] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 P151S protein mutation comprises one or more of the SEQ ID NOs: 600 to 614 and SEQ ID NOs: 825 to 826. In some embodiments, any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 600 to 614 or SEQ ID NOs: 825 to 826. [0772] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 P151S protein mutation comprises one or more of the SEQ ID NOs: - 148 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 600 to 614, SEQ ID NOs: 825 to 826, and SEQ ID NOs: 25730 to 26739. In some embodiments, any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 600 to 614, SEQ ID NOs: 825 to 826, or SEQ ID NOs: 25730 to 26739. [0773] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 P151S protein mutation comprises two or more of the SEQ ID NOs: 600 to 614 and SEQ ID NOs: 825 to 826. In some embodiments, any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 600 to 614 or SEQ ID NOs: 825 to 826. [0774] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 P151S protein mutation comprises two or more of the SEQ ID NOs: 600 to 614, SEQ ID NOs: 825 to 826, and SEQ ID NOs: 25730 to 26739. In some embodiments, any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 600 to 614, SEQ ID NOs: 825 to 826, or SEQ ID NOs: 25730 to 26739. [0775] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R213L protein mutation comprises one or more of the SEQ ID NOs: 615 to 631 and SEQ ID NOs: 827 to 828. In some embodiments, any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 615 to 631 or SEQ ID NOs: 827 to 828. [0776] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R213L protein mutation comprises one or more of the SEQ ID NOs: 615 to 631, SEQ ID NOs: 827 to 828, and SEQ ID NOs: 26740 to 27926. In some embodiments, any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 615 to 631, SEQ ID NOs: 827 to 828, or SEQ ID NOs: 26740 to 27926. - 149 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0777] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R213L protein mutation comprises two or more of the SEQ ID NOs: 615 to 631 and SEQ ID NOs: 827 to 828. In some embodiments, any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 615 to 631 or SEQ ID NOs: 827 to 828. [0778] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R213L protein mutation comprises two or more of the SEQ ID NOs: 615 to 631, SEQ ID NOs: 827 to 828, and SEQ ID NOs: 26740 to 27926. In some embodiments, any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 615 to 631, SEQ ID NOs: 827 to 828, or SEQ ID NOs: 26740 to 27926. [0779] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R249M protein mutation comprises one or more of the SEQ ID NOs: 632 to 648 and SEQ ID NO: 829. In some embodiments, any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 632 to 648 or SEQ ID NO: 829. [0780] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R249M protein mutation comprises one or more of the SEQ ID NOs: 632 to 648, SEQ ID NO: 829, and SEQ ID NOs: 27927 to 29616. In some embodiments, any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 632 to 648, SEQ ID NO: 829, or SEQ ID NOs: 27927 to 29616. [0781] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R249M protein mutation comprises two or more of the SEQ ID NOs: 632 to 648 and SEQ ID NO: 829. In some embodiments, any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 632 to 648 or SEQ ID NO: 829. [0782] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R249M protein mutation comprises two or more of the SEQ ID NOs: - 150 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 632 to 648, SEQ ID NO: 829, and SEQ ID NOs: 27927 to 29616. In some embodiments, any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 632 to 648, SEQ ID NO: 829, or SEQ ID NOs: 27927 to 29616. [0783] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R249S protein mutation comprises one or more of the SEQ ID NOs: 649 to 665 and SEQ ID NO: 830. In some embodiments, any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 649 to 665 or SEQ ID NO: 830. [0784] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R249S protein mutation comprises one or more of the SEQ ID NOs: 649 to 665, SEQ ID NO: 830, and SEQ ID NOs: 29617 to 31034. In some embodiments, any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 649 to 665, SEQ ID NO: 830, or SEQ ID NOs: 29617 to 31034. [0785] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R249S protein mutation comprises two or more of the SEQ ID NOs: 649 to 665 and SEQ ID NO: 830. In some embodiments, any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 649 to 665 or SEQ ID NO: 830. [0786] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R249S protein mutation comprises two or more of the SEQ ID NOs: 649 to 665, SEQ ID NO: 830, and SEQ ID NOs: 29617 to 31034. In some embodiments, any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 649 to 665, SEQ ID NO: 830, or SEQ ID NOs: 29617 to 31034. [0787] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R273L protein mutation comprises one or more of the SEQ ID NOs: 666 to 680 and SEQ ID NO: 831. In some embodiments, any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 666 to 680 or SEQ ID NO: 831. - 151 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0788] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R273L protein mutation comprises one or more of the SEQ ID NOs: 666 to 680, SEQ ID NO: 831, and SEQ ID NOs: 31035 to 31564. In some embodiments, any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 666 to 680, SEQ ID NO: 831, or SEQ ID NOs: 31035 to 31564. [0789] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R273L protein mutation comprises two or more of the SEQ ID NOs: 666 to 680 and SEQ ID NO: 831. In some embodiments, any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 666 to 680 or SEQ ID NO: 831. [0790] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R273L protein mutation comprises two or more of the SEQ ID NOs: 666 to 680, SEQ ID NO: 831, and SEQ ID NOs: 31035 to 31564. In some embodiments, any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 666 to 680, SEQ ID NO: 831, or SEQ ID NOs: 31035 to 31564. [0791] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R280K protein mutation comprises one or more of the SEQ ID NO: 681. In some embodiments, any one of the peptides in the TP53 R280K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 681. [0792] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R280K protein mutation comprises one or more of the SEQ ID NO: 681 and SEQ ID NOs: 31565 to 31615. In some embodiments, any one of the peptides in the TP53 R280K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 681 or SEQ ID NOs: 31565 to 31615. [0793] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R280K protein mutation comprises two or more of the SEQ ID NO: 681. In some embodiments, any one of the peptides in the TP53 R280K composition comprise - 152 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 681. [0794] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 R280K protein mutation comprises two or more of the SEQ ID NO: 681 and SEQ ID NOs: 31565 to 31615. In some embodiments, any one of the peptides in the TP53 R280K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 681 or SEQ ID NOs: 31565 to 31615. [0795] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 S127Y protein mutation comprises one or more of the SEQ ID NOs: 682 to 700 and SEQ ID NO: 832. In some embodiments, any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 682 to 700 or SEQ ID NO: 832. [0796] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 S127Y protein mutation comprises one or more of the SEQ ID NOs: 682 to 700, SEQ ID NO: 832, and SEQ ID NOs: 31616 to 32944. In some embodiments, any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 682 to 700, SEQ ID NO: 832, or SEQ ID NOs: 31616 to 32944. [0797] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 S127Y protein mutation comprises two or more of the SEQ ID NOs: 682 to 700 and SEQ ID NO: 832. In some embodiments, any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 682 to 700 or SEQ ID NO: 832. [0798] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 S127Y protein mutation comprises two or more of the SEQ ID NOs: 682 to 700, SEQ ID NO: 832, and SEQ ID NOs: 31616 to 32944. In some embodiments, any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 682 to 700, SEQ ID NO: 832, or SEQ ID NOs: 31616 to 32944. - 153 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0799] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 S241F protein mutation comprises one or more of the SEQ ID NOs: 701 to 718. In some embodiments, any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 701 to 718. [0800] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 S241F protein mutation comprises one or more of the SEQ ID NOs: 701 to 718 and SEQ ID NOs: 32945 to 33558. In some embodiments, any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 701 to 718 or SEQ ID NOs: 32945 to 33558. [0801] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 S241F protein mutation comprises two or more of the SEQ ID NOs: 701 to 718. In some embodiments, any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 701 to 718. [0802] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 S241F protein mutation comprises two or more of the SEQ ID NOs: 701 to 718 and SEQ ID NOs: 32945 to 33558. In some embodiments, any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 701 to 718 or SEQ ID NOs: 32945 to 33558. [0803] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 V157F protein mutation comprises one or more of the SEQ ID NOs: 719 to 738. In some embodiments, any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 719 to 738. [0804] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 V157F protein mutation comprises one or more of the SEQ ID NOs: 719 to 738 and SEQ ID NOs: 33559 to 34612. In some embodiments, any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, - 154 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 719 to 738 or SEQ ID NOs: 33559 to 34612. [0805] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 V157F protein mutation comprises two or more of the SEQ ID NOs: 719 to 738. In some embodiments, any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 719 to 738. [0806] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 V157F protein mutation comprises two or more of the SEQ ID NOs: 719 to 738 and SEQ ID NOs: 33559 to 34612. In some embodiments, any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 719 to 738 or SEQ ID NOs: 33559 to 34612. [0807] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 V272M protein mutation comprises one or more of the SEQ ID NOs: 739 to 755. In some embodiments, any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 739 to 755. [0808] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 V272M protein mutation comprises one or more of the SEQ ID NOs: 739 to 755 and SEQ ID NOs: 34613 to 35107. In some embodiments, any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 739 to 755 or SEQ ID NOs: 34613 to 35107. [0809] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 V272M protein mutation comprises two or more of the SEQ ID NOs: 739 to 755. In some embodiments, any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 739 to 755. [0810] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 V272M protein mutation comprises two or more of the SEQ ID NOs: - 155 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 739 to 755 and SEQ ID NOs: 34613 to 35107. In some embodiments, any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 739 to 755 or SEQ ID NOs: 34613 to 35107. [0811] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y163C protein mutation comprises one or more of the SEQ ID NOs: 756 to 772 and SEQ ID NO: 833. In some embodiments, any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 756 to 772 or SEQ ID NO: 833. [0812] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y163C protein mutation comprises one or more of the SEQ ID NOs: 756 to 772, SEQ ID NO: 833, and SEQ ID NOs: 35108 to 36047. In some embodiments, any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 756 to 772, SEQ ID NO: 833, or SEQ ID NOs: 35108 to 36047. [0813] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y163C protein mutation comprises two or more of the SEQ ID NOs: 756 to 772 and SEQ ID NO: 833. In some embodiments, any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 756 to 772 or SEQ ID NO: 833. [0814] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y163C protein mutation comprises two or more of the SEQ ID NOs: 756 to 772, SEQ ID NO: 833, and SEQ ID NOs: 35108 to 36047. In some embodiments, any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 756 to 772, SEQ ID NO: 833, or SEQ ID NOs: 35108 to 36047. [0815] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y205C protein mutation comprises one or more of the SEQ ID NOs: 773 to 783. In some embodiments, any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 773 to 783. - 156 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0816] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y205C protein mutation comprises one or more of the SEQ ID NOs: 773 to 783 and SEQ ID NOs: 36048 to 36596. In some embodiments, any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 773 to 783 or SEQ ID NOs: 36048 to 36596. [0817] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y205C protein mutation comprises two or more of the SEQ ID NOs: 773 to 783. In some embodiments, any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 773 to 783. [0818] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y205C protein mutation comprises two or more of the SEQ ID NOs: 773 to 783 and SEQ ID NOs: 36048 to 36596. In some embodiments, any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 773 to 783 or SEQ ID NOs: 36048 to 36596. [0819] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y234C protein mutation comprises one or more of the SEQ ID NOs: 784 to 794 and SEQ ID NO: 834. In some embodiments, any one of the peptides in the TP53 Y234C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 784 to 794 or SEQ ID NO: 834. [0820] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y234C protein mutation comprises one or more of the SEQ ID NOs: 784 to 794, SEQ ID NO: 834, and SEQ ID NOs: 36597 to 36796. In some embodiments, any one of the peptides in the TP53 Y234C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 784 to 794, SEQ ID NO: 834, or SEQ ID NOs: 36597 to 36796. [0821] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y234C protein mutation comprises two or more of the SEQ ID NOs: 784 to 794 and SEQ ID NO: 834. In some embodiments, any one of the peptides in the TP53 - 157 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 Y234C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 784 to 794 or SEQ ID NO: 834. [0822] In some embodiments, the amino acid sequence for a MHC class I peptide composition for the TP53 Y234C protein mutation comprises two or more of the SEQ ID NOs: 784 to 794, SEQ ID NO: 834, and SEQ ID NOs: 36597 to 36796. In some embodiments, any one of the peptides in the TP53 Y234C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 784 to 794, SEQ ID NO: 834, or SEQ ID NOs: 36597 to 36796. [0823] Table 1 shows MHC class I peptide sequences described herein including the respective SEQ ID NO, amino acid sequence corresponding to the SEQ ID NO, protein target (with specific mutation), the seed amino acid sequence (i.e., the amino acid sequence of the wild-type protein fragment), the amino acid substitution (if any) for heteroclitic peptides at positions 2 and C (carboxyl terminus), and notes detailing embodiments in which the peptide may be included in a combined peptide composition as described herein. In some embodiments, any combination of peptides listed in Table 1 (SEQ ID NOs: 1 to 834) may be used to create a combined peptide composition having between about 2 and about 40 peptides. In some embodiments, any one of the peptides (peptides 1 to 834; SEQ ID NOs: 1 to 834) in the combined composition comprises an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to any of SEQ ID NOs: 1 to 834. [0824] Additional amino acid sequences of MHC class I composition peptides are provided in Sequence Listings (SEQ ID NOs: 1280 to 36796). In some embodiments, any combination of MHC class I peptides disclosed herein (SEQ ID NOs: 1 to 834 and SEQ ID NOs: 1280 to 36796) may be used to create a combined peptide composition having between about 2 and about 40 peptides. In some embodiments, any one of the peptides (SEQ ID NOs: 1 to 834 and SEQ ID NOs: 1280 to 36796) in the combined composition comprises or contains an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to any of SEQ ID NOs: 1 to 834 or SEQ ID NOs: 1280 to 36796. [0825] In some embodiments, the composition comprising the MHC class I peptides disclosed herein is an immunogenic composition. In some embodiments, the composition is a vaccine. - 158 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0826] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 1, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2901, A2902, A2911, A3002, A3004, A3009, A3010, B1501, B1502, B1503, B1521, B15220, B1525, B1531, C0214, C0302, C0702, C0705, C1202, C1601, C1602, and C16112. [0827] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 2, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1501, B1502, B1503, B1512, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, C0202, C0210, C0229, C0302, C0705, C1202, C1203, C1601, C1604, and C16112. [0828] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 3, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2901, A2902, A2911, A3002, A3004, A3009, A3010, A3601, B1501, B1502, B1503, B1508, B1511, B1512, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, B4601, C0202, C0210, C0214, C0229, C0302, C0702, C0705, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0829] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 4, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3104, A3402, A3601, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [0830] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 5, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3104, A3401, A3402, A3601, A6602, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. - 159 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0831] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 6, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1501, B1502, B1503, B1517, B1521, B15220, B1525, B1527, B1531, B1532, C0202, C0210, C0229, C0302, C1202, C1504, C1509, C1601, C1602, C16112, and C1646. [0832] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 7, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2902, A2911, A3002, A3004, A3009, A3010, B1501, B1502, B1503, B1517, B1521, B15220, B1525, B1527, B1531, B1532, C0202, C0210, C0229, C0302, C1202, C1504, C1509, C1601, C1602, and C16112. [0833] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 8, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0211, A0214, A02264, A0230, and B1302. [0834] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 9, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0211, A0214, A02264, A0230, and B1302. [0835] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 10, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [0836] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 11, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 160 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2901, A2902, A2911, A3002, A3004, A3009, A3010, A3601, B1501, B1502, B1503, B1508, B1511, B1512, B1517, B1518, B1521, B15220, B1524, B1525, B1527, B1531, B1532, B3501, B3505, B3508, B3532, B3541, B4601, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0702, C0705, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0837] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 12, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1503, B1518, B15220, B1525, B2702, B2704, B2705, B2706, B2707, C0701, C0702, C0704, C0705, C0706, and C0718. [0838] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 13, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B1518, B1521, B15220, B1525, C0214, C0702, and C0705. [0839] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 14, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1516, B1517, B1524, B5703, B5802, C0202, C0210, C0229, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0840] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 15, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, A0206, A0211, A0214, A02264, and B1302. [0841] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 16, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 161 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1517, and B1525. [0842] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 17, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, and C1202. [0843] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 18, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, and C1202. [0844] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 19, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220. [0845] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 20, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220. [0846] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 21, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0847] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 22, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 162 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0848] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 23, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0849] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 24, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0850] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 25, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0851] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 26, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0852] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 27, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402, B1503, B15220, and C1202. [0853] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 28, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 163 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3802. [0854] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 29, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402. [0855] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 30, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402. [0856] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 31, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402. [0857] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 32, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402. [0858] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 33, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0859] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 34, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 164 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0860] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 35, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0861] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 36, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0862] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 37, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0205, B1301, B1503, and B15220. [0863] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 38, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220. [0864] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 39, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1503, B15220, B3801, and B3802. [0865] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 40, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 165 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1503, and B15220. [0866] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 41, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1503, and B15220. [0867] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 42, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0868] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 43, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0869] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 44, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0870] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 45, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0871] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 46, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 166 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0872] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 47, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4006 and B4101. [0873] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 48, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3801 and B3802. [0874] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 49, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3801 and B3802. [0875] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 50, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0205, B1301, B1302, B1303, B1503, B15220, B3801, B3802, and B5201. [0876] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 51, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0207, A0211, A0230, C0403, C0501, and C0509. [0877] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 52, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 167 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0207, A0211, A0230, C0403, C0501, and C0509. [0878] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 53, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0879] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 54, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0880] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 55, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0881] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 56, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0882] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 57, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0883] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 58, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 168 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0884] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 59, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0885] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 60, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0886] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 61, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0887] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 62, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0888] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 63, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4101. [0889] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 64, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 169 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0207, A0211, and A0230. [0890] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 65, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0207, A0211, and A0230. [0891] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 66, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0207, A0211, and A0230. [0892] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 67, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0207, A0211, and A0230. [0893] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 68, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220. [0894] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 69, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220. [0895] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 70, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 170 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220. [0896] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 71, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220. [0897] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 72, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220. [0898] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 73, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0899] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 74, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0900] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 75, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0901] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 76, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 171 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0902] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 77, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0903] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 78, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4006, B4101, and B5001. [0904] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 79, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4006, B4101, and B5001. [0905] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 80, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0206, A0211, A0214, A0230, and B1302. [0906] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 81, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0205, A0206, A0211, A0214, A0230, and B1302. [0907] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 82, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 172 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402. [0908] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 83, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402. [0909] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 84, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0204, A0207, A0211, A0230, C0501, and C0509. [0910] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 85, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0204, A0207, A0211, A0230, C0501, and C0509. [0911] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 86, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0204, A0207, A0211, A0230, C0501, and C0509. [0912] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 87, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509. [0913] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 88, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 173 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509. [0914] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 89, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509. [0915] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 90, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509. [0916] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 91, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509. [0917] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 92, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509. [0918] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 93, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 174 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509. [0919] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 94, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509. [0920] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 95, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509. [0921] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 96, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509. [0922] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 97, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924. [0923] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 98, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924. - 175 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0924] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 99, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924. [0925] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 100, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924. [0926] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 101, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4101. [0927] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 102, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, C0403, C0501, and C0509. [0928] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 103, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, C0102, C0144, C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [0929] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 104, wherein a peptide with this - 176 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, C0102, C0144, C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [0930] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 105, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, C0102, C0144, C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [0931] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 106, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1503, B1510, B1518, B15220, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301. [0932] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 107, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B1518, and B15220. [0933] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 108, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B1518, and B15220. - 177 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0934] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 109, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2403 and A2410. [0935] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 110, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0936] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 111, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0937] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 112, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0938] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 113, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C0801, C0803, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0939] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 114, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 178 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of B1401, B1402, B1503, B1510, B1518, B15220, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301. [0940] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 115, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1503, B1510, B1518, B15220, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301. [0941] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 116, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4101. [0942] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 117, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [0943] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 118, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0207, A0211, C0501, and C0509. [0944] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 119, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0204, A0205, A0206, A0207, A0211, A0214, A0230, C0501, and C0509. [0945] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 120, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 179 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3104, A3402, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [0946] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 121, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, and C1602. [0947] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 122, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1602, and C1646. [0948] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 123, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2603, A2630, A3004, A3009, A3401, A3402, A6601, A6602, A6603, A6801, A7404, C0303, C1202, C1504, C1509, C1602, and C1646. [0949] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 124, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A2603, A2630, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1602, and C1646. - 180 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0950] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 125, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A2603, A2630, A3004, A3009, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, C1202, C1504, C1509, C1602, and C1646. [0951] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 126, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A2603, A2630, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1504, C1509, C1602, and C1646. [0952] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 127, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A2603, A2630, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1602, and C1646. [0953] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 128, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, and C1602. [0954] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 129, wherein a peptide with this - 181 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5501, B5502, and B5601. [0955] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 130, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5501, B5502, and B5601. [0956] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 131, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3401, A6601, A6602, A6603, A7404, C0303, C1202, C1504, C1509, C1602, and C1646. [0957] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 132, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2603, A2630, A3004, A3009, A3401, A6601, A6602, A6603, A7404, C0303, C1202, C1504, C1509, C1602, and C1646. [0958] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 133, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A2603, A2630, A3001, A3004, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1504, C1509, C1602, and C1646. [0959] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 134, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 182 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, and C1602. [0960] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 135, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0202, C0210, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C16112, and C1646. [0961] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 136, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0229, C0303, C1202, C1504, C1509, C1601, C1602, C16112, and C1646. [0962] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 137, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3002, A3004, A3009, A3010, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0229, C0303, C1202, C1602, and C1646. [0963] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 138, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 183 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0229, C0303, C1202, C1602, and C1646. [0964] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 139, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3104, A3401, A3402, A3601, A6601, A6602, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, C0303, and C1602. [0965] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 140, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0966] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 141, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0967] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 142, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3002, A3004, A3009, A3010, A3101, - 184 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0968] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 143, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0969] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 144, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0970] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 145, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, A3002, A3004, A3009, A3010, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A7404, A7410, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0971] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 146, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3002, A3004, A3009, A3101, A3104, - 185 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0972] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 147, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3401, A3402, A6601, A6602, A6603, A7404, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0973] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 148, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3401, A3402, A6601, A6602, A6603, A7404, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0974] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 149, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3002, A3004, A3009, A3010, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [0975] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 150, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0303, C1602, and C1646. - 186 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0976] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 151, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3101, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0202, C0210, C0229, C0303, C1202, C1602, and C1646. [0977] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 152, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3009, A3101, A3104, A3401, A3402, A3601, A6602, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, and C0303. [0978] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 153, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0202, C0210, C0229, C0303, C1202, C1504, C1509, C1602, and C1646. [0979] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 154, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3101, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0202, C0210, C0229, C0303, C1202, C1602, and C1646. - 187 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0980] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 155, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A3001, A3004, A3009, A3101, A3104, A3401, A3402, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, C0303, and C1602. [0981] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 156, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, and A02264. [0982] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 157, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, and A02264. [0983] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 158, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, and A02264. [0984] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 159, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301. [0985] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 160, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 188 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A1101, A1102, A3004, A3009, A3401, A3402, A3601, A6601, A6602, A6603, A7404, C0202, C0210, C0229, C0303, C1202, C1504, C1509, C1602, and C1646. [0986] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 161, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1504, C1509, C1602, and C1646. [0987] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 162, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, A3402, A3601, A7404, C0202, C0210, C0229, C1202, C1504, C1509, C1601, C1602, C16112, and C1646. [0988] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 163, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, and A02264. [0989] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 164, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1525, C0202, C0210, C0229, C0302, and C1202. [0990] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 165, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 189 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A0204, A0205, B1301, B1302, B1303, B1502, B1525, B2705, B4701, B5201, C0704, and C0705. [0991] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 166, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B5703, and B5802. [0992] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 167, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924. [0993] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 168, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3104, A3402, A3601, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, and C0303. [0994] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 169, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301. [0995] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 170, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924. - 190 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [0996] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 171, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, C0303, C1202, C1601, C1602, C16112, and C1646. [0997] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 172, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3401, A3402, A3601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0303, C1202, and C1602. [0998] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 173, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301. [0999] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 174, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1602, and C1646. [1000] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 175, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3303, A3401, A3402, - 191 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1504, C1509, C1601, C1602, C16112, and C1646. [1001] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 176, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1602, and C1646. [1002] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 177, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5201, C0102, C0144, C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C0704, C0801, C0803, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1003] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 178, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, A3402, A3601, A7404, C1202, C1504, C1509, C1602, and C1646. [1004] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 179, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202 and A0205. [1005] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 180, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 192 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1525, B2705, B4701, B5201, C0704, and C0705. [1006] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 181, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5802. [1007] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 182, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, A3601, A6601, A6602, A6603, A7404, C0303, C1202, C1504, C1509, C1601, C1602, C16112, and C1646. [1008] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 183, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924. [1009] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 184, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, and B7301. [1010] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 185, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. - 193 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1011] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 186, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3402, A3601, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1012] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 187, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601 and C0303. [1013] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 188, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601 and C0303. [1014] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 189, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, A7404, and C0303. [1015] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 190, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5502 and B5601. [1016] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 191, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5502 and B5601. - 194 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1017] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 192, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5703 and B5802. [1018] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 193, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5703 and B5802. [1019] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 194, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1020] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 195, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, C0303, and C1602. [1021] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 196, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, C0303, and C1602. [1022] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 197, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, A7404, C0303, and C1602. - 195 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1023] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 198, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5601. [1024] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 199, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402. [1025] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 200, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402. [1026] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 201, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5703, B5802, C1602, and C1646. [1027] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 202, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5703, B5802, and C1602. [1028] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 203, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, C0102, C0103, C0144, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0702, C0704, C0705, C0801, C0803, - 196 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1029] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 204, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0202, C0210, C0214, C0229, C0302, C0602, C0702, C0705, C1202, C1203, C1402, C1403, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [1030] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 205, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0102, C0144, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0702, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1031] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 206, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0102, C0144, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0702, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1032] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 207, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0602, C0702, C0705, C1202, C1203, C1502, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. - 197 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1033] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 208, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2601 and A3401. [1034] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 209, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6802 and A6827. [1035] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 210, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2601 and A3401. [1036] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 211, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A2901, A2902, A2911, A3002, A3009, A3010, A3601, B1502, B1521, B1525, B1531, B3508, B5704, C0202, C0210, C0214, C0229, C0302, C0403, C0501, C0509, C0705, C0801, C0802, C0803, C1202, C1504, C1509, C1601, C1602, C16112, and C1646. [1037] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 212, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A2901, A2902, A2911, A3002, A3004, A3009, A3010, A3601, A7404, A7410, B1502, B1521, B1525, B1531, B3508, B5704, C0202, C0210, C0214, C0229, C0302, C0403, C0501, C0509, C0801, C0802, C0803, C1202, C1504, C1509, C1601, C1602, C16112, and C1646. - 198 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1038] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 213, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0102, C0103, C0144, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0702, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1039] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 214, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0102, C0103, C0144, C0202, C0210, C0214, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0702, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1040] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 215, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, B4601, C0202, C0210, C0214, C0229, C0302, C0602, C0702, C0705, C1202, C1203, C1402, C1403, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [1041] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 216, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, C0214, C0602, C0702, C0704, C0705, C1402, and C1403. [1042] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 217, wherein a peptide with this - 199 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B15220, B1525, B1531, C0102, C0144, C0214, C0302, C0602, C0702, C0704, C0705, C1202, C1203, C1402, C1403, C1601, C1602, C1604, C16112, and C1646. [1043] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 218, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0207, A3601, B1502, B1525, B1531, C0202, C0210, C0214, C0229, C0401, C0403, C0407, C0501, C0509, C0705, C0801, C0802, C0803, C1402, C1403, C1504, C1509, C1601, C1602, C16112, and C1646. [1044] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 219, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0109, A0207, A3601, B1502, B1525, B1531, C0202, C0210, C0214, C0229, C0302, C0401, C0403, C0407, C0501, C0509, C0705, C0801, C0802, C0803, C1202, C1402, C1403, C1504, C1509, C1601, C1602, C16112, and C1646. [1045] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 220, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, A0207, A2901, A2902, A2911, A3002, A3004, A3009, A3010, A3601, A7404, A7410, A8001, B1501, B1502, B1512, B1521, B1525, B1527, B1531, B1532, B3508, B4701, B5704, C0202, C0210, C0214, C0229, C0302, C0401, C0403, C0407, C0501, C0509, C0705, C0801, C0802, C0803, C1202, C1402, C1403, C1504, C1509, C1601, C1602, C16112, and C1646. [1046] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 221, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 200 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A2901, A2902, A2911, B1502, B1521, B1525, B1531, B1801, B1802, B3701, B4402, B4404, B4427, B4701, and C1202. [1047] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 222, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2901, A2902, A2911, A3601, B1502, B1521, B1525, B1531, and C1202. [1048] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 223, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4402, B4403, B4404, B4407, and B4427. [1049] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 224, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0211, A02264, and A0230. [1050] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 225, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0211, A02264, and A0230. [1051] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 226, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B3503, B4201, B4202, B5501, B5502, B5601, B5604, B5610, B6701, B8101, and B8103. [1052] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 227, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 201 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0211, B0702, B0705, B3503, B3910, B4201, B4202, B5501, B5502, B5601, B5604, B5610, B6701, B8101, and B8103. [1053] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 228, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5703, and B5801. [1054] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 229, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5703, and B5801. [1055] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 230, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5703, and B5801. [1056] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 231, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0211, A02264, and A0230. [1057] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 232, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1801, B1802, B1803, B3701, B4402, B4403, B4404, B4407, and B4427. [1058] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 233, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 202 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1525, C0202, C0210, C0214, C0217, C0229, C0302, C0705, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [1059] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 234, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1516, B5701, B5702, B5703, B5704, B5801, and B5802. [1060] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 235, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1802, B3701, B4002, B40114, B4102, B4402, B4403, B4404, B4405, B4407, B4427, and B4901. [1061] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 236, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4002, B40114, B4102, B4402, B4403, B4404, B4405, B4407, B4427, and B4901. [1062] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 237, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B3701, B4002, and B4102. [1063] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 238, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5701, B5703, B5704, and B5802. [1064] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 239, wherein a peptide with this - 203 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0211, A02264, B0702, B0705, B4201, B5501, B5502, B5601, B5604, B5610, and B6701. [1065] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 240, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, and B1302. [1066] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 241, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A7404, B1302, and B1303. [1067] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 242, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A7404, B1302, B1303, and B5201. [1068] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 243, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, B1301, B1302, B1303, and B5201. [1069] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 244, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 204 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, and B1302. [1070] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 245, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, A0211, and A02264. [1071] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 246, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, A0211, and A02264. [1072] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 247, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, A0211, and A02264. [1073] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 248, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3501, B3508, and B3541. [1074] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 249, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1302, B3701, B4002, B4006, B40114, B4016, B4101, B4102, B4901, B5201, and C0704. [1075] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 250, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 205 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1302, B3701, B4002, B4006, B40114, B4016, B4101, B4102, B4901, B5201, and C0704. [1076] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 251, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1302, B3701, B4002, B4006, B4102, B4901, B5201, and C0704. [1077] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 252, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B3503, B4201, B5108, B5501, B5502, B5601, B5604, B5610, and B6701. [1078] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 253, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3910, B4201, B4202, B5108, B5109, B5301, B5501, B5502, B5601, B5604, B5610, and B6701. [1079] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 254, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3501, B3503, B3505, B3508, B3532, B3541, B5301, and B5610. [1080] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 255, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3501, B3503, B3505, B3508, B3532, B3541, B4201, B5301, B5501, B5502, B5601, B5604, and B5610. [1081] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 256, wherein a peptide with this - 206 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1082] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 257, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1083] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 258, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1084] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 259, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1085] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 260, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1086] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 261, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1087] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 262, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 207 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1088] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 263, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1089] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 264, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4402, B4403, B4404, B4405, B4407, and B4427. [1090] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 265, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205. [1091] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 266, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205. [1092] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 267, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0303, C1602, and C1646. [1093] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 268, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 208 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0303, C1602, and C1646. [1094] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 269, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, C1602, and C1646. [1095] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 270, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4101. [1096] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 271, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4402, B4403, B4404, B4405, B4407, and B4427. [1097] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 272, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2403, A2410, A3004, A3009, A3010, A3201, A7410, B1301, B1516, B1517, B1524, B1525, B5701, B5702, B5703, B5704, B5801, and B5802. [1098] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 273, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3201, A3601, A7404, A7405, A7410, B1301, B1501, B1502, B1503, B1516, B1517, B15220, B1524, B1525, B1531, B5701, B5703, B5704, B5802, C0202, C0210, C0214, C0229, C0302, C0705, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. - 209 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1099] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 274, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1100] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 275, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1101] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 276, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3201, A3601, A7410, B1301, B1516, B1517, B1524, B5701, B5702, B5703, B5704, B5801, B5802, C1504, C1509, C1601, C1602, C16112, and C1646. [1102] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 277, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1103] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 278, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3201, A7410, B1301, B1516, B1517, B1524, B1525, B5701, B5702, B5703, B5704, B5801, B5802, C1504, C1509, C1602, and C1646. [1104] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 279, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 210 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A2403, A2410, A2901, A2902, A2911, A3002, A3004, A3009, A3010, B5701, B5703, and C0705. [1105] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 280, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1106] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 281, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3002, A3004, A3009, A3010, A3201, A3601, A7410, B1301, B1501, B1502, B1503, B1516, B1517, B15220, B1524, B1525, B1531, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0214, C0229, C0302, C0701, C0705, C0706, C0718, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, and C1646. [1107] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 282, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3004, A3009, A3201, A7404, B1301, B1502, B1516, B1517, B1525, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0214, C0229, C0302, C0701, C0705, C0706, C0718, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, and C1646. [1108] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 283, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3201, A3601, A7404, A7405, A7410, B1501, B1502, B1503, B1516, B1517, B15220, B1524, B1525, B1531, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0214, C0229, C0302, C0701, C0705, C0706, C0718, C1202, C1203, C1502, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. - 211 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1109] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 284, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4002, B4016, B4101, and B4102. [1110] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 285, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4002, B4016, B4101, B4102, and C0704. [1111] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 286, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3201, A3601, A7404, A7405, A7410, B1301, B1501, B1502, B1503, B1516, B1517, B15220, B1524, B1525, B1531, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0229, C0302, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [1112] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 287, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2901, A2902, A2911, A3002, A3004, A3009, A3010, A3201, A3601, A7404, A7410, B1301, B1501, B1502, B1503, B1517, B15220, B1524, B1525, B1531, B5703, B5704, B5802, C0202, C0210, C0214, C0229, C0302, C0701, C0705, C0706, C0718, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [1113] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 288, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3002, A3004, A3009, A3010, B1503, B15220, B1525, C0214, C0701, C0705, C0706, and C0718. - 212 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1114] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 289, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3002, A3004, A3009, A3010, A3201, A7404, A7405, B1301, B1516, B1517, B1525, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0214, C0229, C0302, C0705, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, and C1646. [1115] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 290, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4402, B4403, B4404, B4407, and B4427. [1116] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 291, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A6802, A6827, and A6901. [1117] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 292, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A6802, A6827, and A6901. [1118] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 293, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0211, A0214, A02264, and A0230. [1119] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 294, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 213 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, and A0230. [1120] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 295, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1302, B1303, B1802, B3701, B4001, B4002, B4006, B40114, B4016, B4101, B4102, B4402, B4403, B4404, B4407, B4415, B4427, B4501, B4507, B4701, B4703, B4901, and B5001. [1121] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 296, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1502, B1503, B1518, B15220, B1525, B1531, B1801, B1802, B1803, B2706, B3701, B3802, B4001, B4002, B4006, B40114, B4012, B4016, B4101, B4102, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4701, B4703, B4803, B4901, B5001, B5201, C0701, C0702, C0704, C0705, C0706, C0718, and C1202. [1122] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 297, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1503, B15220, B1802, B1803, B3701, B3802, B4001, B4002, B4006, B40114, B4012, B4016, B4101, B4102, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4701, B4703, B4803, B4901, B5001, B5201, and C0704. [1123] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 298, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1502, B1503, B1518, B15220, B1525, B1531, B1801, B1802, B1803, B3701, B4001, B4002, B4006, B40114, B4101, B4102, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4701, B4703, B4901, B5001, C0701, C0702, C0705, C0706, C0718, and C1202. - 214 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1124] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 299, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1502, B1503, B1518, B15220, B1525, B1531, B2706, B3701, B3802, B4001, B4002, B4006, B40114, B4012, B4016, B4101, B4102, B4427, B4701, B4703, B4801, B4803, B4901, B5001, B5201, C0701, C0702, C0704, C0705, C0706, and C0718. [1125] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 300, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1502, B1503, B1518, B15220, B1525, B1531, B2706, B3701, B3802, B4001, B4002, B4006, B40114, B4012, B4016, B4101, B4102, B4427, B4701, B4703, B4801, B4803, B4901, B5001, B5201, C0701, C0702, C0704, C0705, C0706, C0718, and C1202. [1126] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 301, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1301, B5703, and B5802. [1127] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 302, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3009, A3201, B1301, B1501, B1502, B1503, B15220, B1525, C1202, C1504, and C1509. [1128] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 303, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B5703, and B5802. - 215 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1129] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 304, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1503, B1518, B15220, B1525, B1531, B4701, B4703, C0701, C0702, C0705, C0706, C0718, and C1202. [1130] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 305, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4001, B4002, B4006, B40114, B4016, B4101, B4102, B4415, B4427, B4501, B4507, B4901, and B5001. [1131] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 306, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1503, B15220, B1801, B1802, B1803, B3701, B4001, B4002, B4006, B40114, B4012, B4016, B4101, B4102, B4402, B4403, B4404, B4405, B4407, B4410, B4415, B4427, B4501, B4507, B4701, B4703, B4803, B4901, B5001, B5201, and C0704. [1132] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 307, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B1503, B15220, B1525, B2706, B3701, B3802, B4002, B4006, B40114, B4012, B4016, B4101, B4102, B4701, B4703, B4801, B4803, B4901, B5001, B5201, C0701, C0702, C0704, C0705, C0706, and C0718. [1133] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 308, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, and A7404. - 216 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1134] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 309, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, and A7404. [1135] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 310, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202. [1136] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 311, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202. [1137] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 312, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220. [1138] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 313, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3201, B1301, B1516, B1517, B1525, B5701, B5702, B5703, B5704, B5801, and B5802. [1139] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 314, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 217 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A3004, A3009, A3201, B1301, B1516, B1517, B1525, B5701, B5702, B5703, B5704, B5801, and B5802. [1140] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 315, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3201, B1301, B1516, B1517, B1524, B5701, B5702, B5703, B5704, B5801, and B5802. [1141] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 316, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220. [1142] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 317, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503 and B15220. [1143] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 318, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, and A7404. [1144] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 319, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3201, B1301, B1516, B1517, B1524, B5701, B5702, B5703, B5704, B5801, and B5802. [1145] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 320, wherein a peptide with - 218 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1301, B1503, B15220, B1524, B4402, B4403, B4404, B4407, B4427, B4701, B4703, B5701, B5702, B5703, B5704, B5801, and B5802. [1146] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 321, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3201, B1501, B1503, B1512, B15220, B1524, B1525, B1527, B1531, and B1532. [1147] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 322, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3201, B1301, B1302, B1303, B1501, B1503, B1512, B15220, B1524, B1525, B1527, B1531, B1532, B2702, B4427, B4701, and B4703. [1148] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 323, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, A3201, B1301, B1501, B1503, B1512, B15220, B1524, B1525, B1527, B1531, B1532, B2702, B4427, B4701, and B4703. [1149] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 324, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, and B2702. [1150] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 325, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 219 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of B1401, B1402, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, C0702, C0704, and C0705. [1151] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 326, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3401, A3402, A6602, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1152] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 327, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3401, A3402, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1153] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 328, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, and A6801. [1154] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 329, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6802 and A6827. [1155] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 330, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A7404, B1302, B1303, and B5201. - 220 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1156] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 331, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0211, A0214, A02264, and A0230. [1157] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 332, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0211, A0214, A02264, and A0230. [1158] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 333, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2403, and A2410. [1159] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 334, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801, C0102, C0144, C0202, C0210, C0217, C0229, C0317, C0602, C1202, C1203, C1505, C1601, C1602, C1604, C16112, and C1646. [1160] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 335, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1161] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 336, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 221 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5802. [1162] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 337, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, B1302, B1303, and B5201. [1163] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 338, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801, C0102, C0144, C0202, C0210, C0217, C0229, C0317, C0602, C1202, C1203, C1505, C1601, C1602, C1604, C16112, and C1646. [1164] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 339, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801, C0102, C0144, C0202, C0210, C0217, C0229, C0317, C0602, C1202, C1203, C1505, C1601, C1602, C1604, C16112, and C1646. [1165] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 340, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1166] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 341, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5702, B5703, B5704, B5801, and B5802. - 222 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1167] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 342, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1168] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 343, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3303, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1169] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 344, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1170] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 345, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1171] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 346, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1172] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 347, wherein a peptide with this - 223 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1173] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 348, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4102, B4402, B4403, B4404, B4405, B4407, B4427, and B4901. [1174] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 349, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5702, C0403, C0501, C0509, C0801, C0802, C0803, C0812, and C1505. [1175] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 350, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, B1801, B1802, B4402, B4403, B4404, B4407, B4427, and B4703. [1176] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 351, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1177] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 352, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601 and C1602. - 224 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1178] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 353, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4002, B4006, B40114, B4101, B4102, B4415, B4901, and B5001. [1179] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 354, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1801, B1802, B1803, B3701, B4002, B40114, B4102, B4402, B4403, B4404, B4405, B4407, B4427, and B4901. [1180] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 355, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1801, B1802, B1803, B3701, B4002, B40114, B4102, B4402, B4403, B4404, B4405, B4407, B4427, and B4901. [1181] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 356, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B4402, B4403, B4404, B4407, B4427, B5701, B5703, B5704, B5801, and B5802. [1182] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 357, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5701, B5703, B5704, B5801, and B5802. [1183] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 358, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 225 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B5701, B5703, B5704, B5801, and B5802. [1184] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 359, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1185] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 360, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1186] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 361, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, B1801, B1802, B1803, B3701, B4002, B4102, B4402, B4403, B4404, B4407, B4427, B4701, and B4703. [1187] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 362, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, B1801, B1802, B1803, B3701, B4002, B4102, B4402, B4403, B4404, B4407, B4427, B4701, and B4703. [1188] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 363, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. - 226 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1189] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 364, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1190] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 365, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1191] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 366, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1192] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 367, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4402, B4403, B4404, B4405, B4407, and B4427. [1193] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 368, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601 and C1602. [1194] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 369, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 227 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1195] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 370, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4101. [1196] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 371, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1801, B1802, B1803, B3701, B4002, B4102, B4402, B4403, B4404, B4405, B4407, B4427, and B4901. [1197] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 372, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1801, B1802, B1803, B3701, B4002, B4102, B4402, B4403, B4404, B4405, B4407, B4427, and B4901. [1198] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 373, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B3701, B4427, and B5703. [1199] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 374, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B3701, B4002, and B4102. - 228 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1200] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 375, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5701, B5703, B5704, B5801, and B5802. [1201] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 376, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B5701, B5703, B5704, B5801, and B5802. [1202] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 377, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A6801, C0303, and C1602. [1203] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 378, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A6801, C0303, and C1602. [1204] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 379, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A6801, C0303, and C1602. [1205] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 380, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4002, B4006, B40114, B4101, B4102, B4415, B4501, B4507, B4901, and B5001. - 229 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1206] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 381, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4001, B4002, B4006, B40114, B4016, B4101, B4102, B4402, B4403, B4404, B4405, B4407, B4415, B4427, B4501, B4507, B4901, and B5001. [1207] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 382, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4001, B4002, B4006, B40114, B4016, B4101, B4102, B4402, B4403, B4404, B4405, B4407, B4415, B4427, B4501, B4507, B4901, and B5001. [1208] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 383, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4101, B4102, B4402, B4403, B4404, B4405, B4407, B4415, B4427, and B4901. [1209] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 384, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3701, B4002, B4006, B40114, B4101, B4102, B4402, B4403, B4404, B4405, B4407, B4415, B4427, and B4901. [1210] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 385, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, A7404, C0202, C0210, C0229, C0302, C1202, C1504, C1509, C1601, C1602, C16112, and C1646. [1211] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 386, wherein a peptide with this - 230 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, C1602, and C1646. [1212] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 387, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, and A3305. [1213] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 388, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, and A6801. [1214] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 389, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, and A6801. [1215] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 390, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, and A6801. [1216] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 391, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, and A3305. [1217] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 392, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 231 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B2702, B2703, B2704, B2705, B2706, B2707, B3906, B3924, B7301, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1218] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 393, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B2702, B2703, B2704, B2705, B2706, B2707, B3924, B7301, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1219] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 394, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1220] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 395, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, A6601, A6602, A6603, and A6801. [1221] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 396, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, A6601, A6602, A6603, and A6801. [1222] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 397, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, A6601, A6602, A6603, and A6801. - 232 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1223] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 398, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B2702, B2703, B2704, B2705, B2706, B2707, B3924, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1224] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 399, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B2702, B2703, B2704, B2705, B2706, B2707, B3906, B3924, B7301, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1225] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 400, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2703, B2704, B2705, B2706, B2707, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1226] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 401, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101 and A3104. [1227] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 402, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101 and A3104. [1228] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 403, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 233 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101 and A3104. [1229] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 404, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, and A3305. [1230] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 405, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, A3305, A3401, and A6801. [1231] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 406, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B2702, B2703, B2704, B2705, B2706, B2707, B3924, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1232] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 407, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B2702, B2703, B2704, B2705, B2706, B2707, B3906, B3924, B7301, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1233] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 408, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B2702, B2703, B2704, B2705, B2706, B2707, B3924, B7301, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. - 234 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1234] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 409, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, and A3305. [1235] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 410, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3303, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1236] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 411, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1237] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 412, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, and A3305. [1238] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 413, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, A6602, and A6603. [1239] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 414, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, A6602, and A6603. - 235 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1240] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 415, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B2702, B2704, B2705, B2706, B2707, B3906, B3924, B7301, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1241] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 416, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B2702, B2703, B2704, B2705, B2706, B2707, B3906, B3924, B7301, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1242] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 417, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2703, B2704, B2705, B2706, B2707, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1243] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 418, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101. [1244] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 419, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101. [1245] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 420, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 236 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101. [1246] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 421, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0302, C0303, C0304, C1202, C1203, C1402, C1403, C1601, and C16112. [1247] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 422, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, C0302, C0303, C0304, C1202, C1203, C1402, C1403, C1601, and C16112. [1248] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 423, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0211, A02264, and A0230. [1249] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 424, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0211, A02264, A0230, B1501, B1503, B15220, and B1525. [1250] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 425, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0211, A02264, and A0230. [1251] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 426, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 237 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1501, B1502, B1503, B15220, B1525, B1527, and B1532. [1252] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 427, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1501, B1502, B1503, B15220, B1525, C0302, C1202, C1402, and C1403. [1253] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 428, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0302, C0303, C0304, C1203, C1601, and C16112. [1254] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 429, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2402, A2403, A2410, B1503, B15220, C0302, C1402, and C1403. [1255] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 430, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2402, A2403, A2410, B1503, B15220, C0302, C1402, and C1403. [1256] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 431, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, C0702, C1402, and C1403. [1257] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 432, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 238 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0211, and A02264. [1258] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 433, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1501, B1502, B1503, B15220, B1525, B1527, and B1532. [1259] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 434, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0211, and A02264. [1260] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 435, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0211, and A02264. [1261] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 436, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0211, and A02264. [1262] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 437, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0211, and A02264. [1263] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 438, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 239 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0211, and A02264. [1264] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 439, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0211, and A02264. [1265] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 440, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0211, and A02264. [1266] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 441, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, and A3305. [1267] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 442, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, and A3305. [1268] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 443, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, A0206, A6802, A6827, A6901, B5401, C1203, C1601, C1604, and C16112. [1269] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 444, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 240 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, A0206, A6802, A6827, A6901, C1203, and C1604. [1270] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 445, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6802, A6827, A6901, and B5401. [1271] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 446, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6801, C1203, C1601, C1604, and C16112. [1272] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 447, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3402, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1273] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 448, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A3001, A3101, A3104, A3303, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1274] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 449, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A6802, and A6827. [1275] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 450, wherein a peptide with this - 241 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A6802, and A6827. [1276] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 451, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, and A7405. [1277] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 452, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3303, A3401, A3402, A6602, A6603, A6801, and A7405. [1278] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 453, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1801, B1802, B1803, B4002, B4006, B4101, B4102, B4415, B4901, and B5001. [1279] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 454, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1801, B1802, and B1803. [1280] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 455, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, A0206, A6801, A6802, A6827, A6901, C1203, C1601, C1604, and C16112. [1281] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 456, wherein a peptide with this - 242 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3402, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1282] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 457, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3303, A3401, A3402, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1283] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 458, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3009, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, and B2705. [1284] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 459, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, and B2705. [1285] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 460, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, and B2705. - 243 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1286] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 461, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, and B2705. [1287] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 462, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, and B2705. [1288] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 463, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3004, and A3009. [1289] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 464, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, and B2705. [1290] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 465, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0305, A3001, A3009, A3101, A3104, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. - 244 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1291] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 466, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801 and B2705. [1292] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 467, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801, B1401, B1402, and B2705. [1293] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 468, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4006, B4101, and B4415. [1294] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 469, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2703, B2704, B2705, B2707, C0701, C0705, C0706, and C0718. [1295] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 470, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2703, B2704, B2705, B2707, C0701, C0705, C0706, and C0718. [1296] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 471, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3104, A3402, A3601, A74, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. - 245 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1297] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 472, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, and B2705. [1298] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 473, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1299] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 474, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, B0801, B4201, C1601, and C16112. [1300] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 475, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801, B4201, C1601, and C16112. [1301] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 476, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C1203, C1601, C1604, and C16112. [1302] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 477, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 246 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of C1203, C1601, C1604, and C16112. [1303] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 478, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3303, A3401, A3402, and A6801. [1304] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 479, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1305] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 480, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3101, A3104, A3301, A3303, A3305, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1306] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 481, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, A3104, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1307] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 482, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1501, B1502, B1503, B15220, B1525, and B1527. - 247 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1308] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 483, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0204, A0205, A0207, A0211, and A02264. [1309] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 484, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, A3104, A3401, A3402, A6602, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1310] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 485, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3101, A3104, A3402, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1311] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 486, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1312] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 487, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3104, A3401, A3402, A3601, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1313] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 488, wherein a peptide with this - 248 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, A3104, A3401, A3402, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1314] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 489, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3303, A3401, A3402, and A6801. [1315] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 490, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3402, A3601, A6603, and A7404. [1316] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 491, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3303, A3401, A3402, and A6801. [1317] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 492, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3303, A3401, A3402, and A6801. [1318] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 493, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0705, B0801, and B4201. [1319] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 494, wherein a peptide with this - 249 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0705, B0801, and B4201. [1320] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 495, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C1203, C1601, C1604, and C16112. [1321] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 496, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3104, A3401, A3402, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1322] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 497, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1323] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 498, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3101, A3104, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1324] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 499, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 250 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1325] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 500, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1326] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 501, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, A0211, and A02264. [1327] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 502, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1501, B1502, B1503, B15220, B1525, and B1527. [1328] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 503, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0303 and C1602. [1329] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 504, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0303 and C1602. [1330] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 505, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 251 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A0302, A1101, A1102, A3101, A3104, A3402, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1331] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 506, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1332] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 507, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1333] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 508, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3101, A3104, A3301, A3303, A3305, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, and C0303. [1334] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 509, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A7404, A7405, A7413, and C1602. [1335] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 510, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 252 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1336] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 511, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801, C0704, C1601, C1602, C16112, and C1646. [1337] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 512, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, and A3305. [1338] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 513, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, and A6801. [1339] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 514, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6801. [1340] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 515, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, and A3305. [1341] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 516, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 253 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1342] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 517, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101 and A3104. [1343] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 518, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1344] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 519, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1345] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 520, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2704, B2705, B2706, B2707, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1346] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 521, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2704, B2705, B2706, B2707, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1347] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 522, wherein a peptide with this - 254 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2704, B2705, B2706, B2707, B7301, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1348] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 523, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2704, B2705, B2706, B2707, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1349] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 524, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2704, B2705, B2706, B2707, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1350] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 525, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101 and A3104. [1351] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 526, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101 and A3104. [1352] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 527, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101 and A3104. - 255 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1353] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 528, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101 and A3104. [1354] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 529, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101 and A3104. [1355] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 530, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0207, A0211, A02264, A0230, B1301, B1302, B1303, B5201, C1502, C1505, C1602, C1646, C17, C1701, C1702, C1703, C1704, and C1705. [1356] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 531, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, and B1302. [1357] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 532, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0207, A0211, A02264, A0230, B1301, B1302, B1303, B5201, C1502, C1505, C1602, C1646, C1701, C1702, C1703, C1704, and C1705. [1358] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 533, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 256 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A3101, A3104, A3303, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, and A7413. [1359] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 534, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0211, A02264, A0230, B1301, B1302, and B1303. [1360] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 535, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A3101, A3104, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, and A7413. [1361] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 536, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0211, A02264, A0230, A3201, B1301, B1302, and B1303. [1362] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 537, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3303, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1363] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 538, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 257 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A0301, A0302, A0305, A3101, A3104, A3303, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, and A7413. [1364] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 539, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3303, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1365] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 540, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B0801, B4201, B4202, B5101, B5102, B5105, B5108, B5109, B5501, B5502, B5601, B5604, B5610, C0102, and C0144. [1366] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 541, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5101, B5102, B5107, B5108, and B5109. [1367] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 542, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, A3305, A3401, and A6801. [1368] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 543, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1302, B1303, B5201, C1502, C1505, C1701, C1702, C1703, C1704, C1705, and C1706. [1369] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 544, wherein a peptide with this - 258 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1301, B1302, B5201, C1502, C1505, C1602, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1370] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 545, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5101, B5102, B5107, B5108, B5109, B5201, C0102, C0103, C0144, C0202, C0210, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0403, C0501, C0509, C0602, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1371] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 546, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1301, and B1525. [1372] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 547, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, and C0303. [1373] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 548, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0207, A0211, A0214, A02264, A0230, and B1302. [1374] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 549, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 259 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1375] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 550, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3101, A3104, A3303, A3401, A3402, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1376] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 551, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, and B1302. [1377] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 552, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3104, A3401, A3402, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, and C0303. [1378] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 553, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A6602, A6603, and A6801. [1379] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 554, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 260 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A3401, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1380] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 555, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1381] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 556, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4201, B5108, B5201, B5610, C0102, C0103, C0144, C0602, C0704, C0801, C0803, C1505, C1602, and C1646. [1382] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 557, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B3503, B4201, B4202, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5501, B5502, B5601, B5604, B5610, B6701, C0102, C0103, C0144, C0602, C0704, C0801, C0803, C1505, C1602, and C1646. [1383] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 558, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, A3305, A3401, A3402, A6601, A6602, and A6801. [1384] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 559, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, C0102, and C0144. - 261 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1385] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 560, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, A6602, A6603, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, C0102, C0144, C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [1386] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 561, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, A6603, A7404, A7405, C0102, C0144, C0202, C0210, C0229, C0302, C0303, C0304, C0305, C0317, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [1387] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 562, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1403, B1510, B1537, B2706, B3801, B3802, B3901, B3905, B3906, B3909, B3924, B7301, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1388] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 563, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1403, B1510, B1537, B2702, B2703, B2704, B2705, B2706, B2707, B3801, B3802, B3901, B3905, B3906, B3909, B3924, B7301, C0214, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1389] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 564, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, - 262 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 A3004, A3009, A3201, A7404, B1301, B1302, B1303, B1501, B1502, B1525, B5201, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0403, C0404, C0501, C0509, C0602, C0702, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1390] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 565, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3104, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1391] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 566, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A3004, A3009, A3201, A7404, B1301, B1302, B1303, B1525, B5201, C0202, C0210, C0229, C0501, C0509, C0704, C0801, C0803, C1502, C1504, C1505, C1509, C1602, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1392] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 567, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, B1301, B1302, B1303, B1501, B1525, B5201, C0202, C0210, C0229, C0602, C0704, C0801, C0803, C1202, C1502, C1505, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1393] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 568, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, A6602, A6603, A7404, B1502, B1516, B1517, B1525, B4601, B5802, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0801, - 263 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 C0803, C1202, C1203, C1402, C1403, C1502, C1504, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, and C1705. [1394] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 569, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2403, A2410, C0102, C0144, C0214, C0602, C0704, C1402, C1403, C1601, and C16112. [1395] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 570, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, and A3104. [1396] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 571, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, and A3104. [1397] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 572, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A3009, B1502, B1521, B1525, B1531, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0803, C0812, C1202, C1203, C1402, C1403, C1504, C1509, C1601, C1602, C1604, C16112, C1646, C18, C1801, C1802, and C1803. [1398] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 573, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0204, A0205, A3009, B1301, B1501, B1502, B1525, C0102, C0103, C0144, C0202, - 264 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0403, C0404, C0501, C0509, C0602, C0702, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1399] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 574, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1521, B1525, B1531, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, and C1803. [1400] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 575, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3009, B1502, B1521, B1525, B1531, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, and C1803. [1401] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 576, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A3009, B0801, B1502, B1521, B1525, B1531, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, - 265 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, and C1803. [1402] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 577, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A3009, B0801, B1502, B1521, B1525, B1531, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, and C1803. [1403] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 578, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1521, C0214, C0404, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C1202, C1203, C1402, C1403, C1504, C1509, C1602, C1604, C1646, and C1803. [1404] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 579, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0214, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1405] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 580, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3009, B1502, B1521, B1525, B1531, C0202, C0210, C0214, C0229, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C1202, C1203, C1402, C1403, C1504, C1509, C1602, C1604, and C1646. - 266 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1406] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 581, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1521, B1525, B1531, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, and C1803. [1407] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 582, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A3009, B0801, B1502, B1521, B1525, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0401, C0403, C0404, C0407, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, C1707, C18, C1801, C1802, and C1803. [1408] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 583, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A7404, B1301, B1302, B1303, B5201, C1502, C1505, C1701, C1702, C1703, C1704, and C1705. [1409] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 584, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3104, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. - 267 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1410] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 585, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A3004, A3009, A3201, A7404, B1301, B1302, B1303, B1525, B5201, C1502, and C1505. [1411] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 586, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A3402, A6601, A6602, A6603, A7404, B1516, B1517, B1525, B5703, B5802, C0202, C0210, C0217, C0229, C0302, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [1412] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 587, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, and A3104. [1413] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 588, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A3009, B1525, C0102, C0144, C0214, C0302, C0401, C0404, C0407, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C1203, C1402, C1403, C1601, C1602, C1604, C16112, C1646, C18, C1801, and C1802. [1414] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 589, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3009, B1502, B1503, B1511, B1517, B1521, B15220, B1525, B1531, B3501, B3508, B4601, B5704, B5802, C0102, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0701, C0702, C0705, C0706, C0718, C0801, C0803, C0812, - 268 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1415] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 590, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2407, B1517, B1525, B5702, B5703, B5802, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0403, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1416] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 591, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, B1302, C0202, C0210, C0229, C1502, C1504, C1505, C1509, C1601, C1602, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1417] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 592, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, A6603, A6802, A6827, C0202, C0210, C0229, C1203, C1502, C1505, C1602, C1604, and C1646. [1418] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 593, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1525, C0102, C0103, C0144, C0214, C0302, C0305, C0317, C0401, C0404, C0407, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0803, C1203, C1402, C1403, C1601, C1602, C1604, C16112, C1646, C18, C1801, C1802, and C1803. - 269 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1419] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 594, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, B1525, C0102, C0103, C0144, C0214, C0302, C0305, C0317, C0401, C0404, C0407, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0803, C1203, C1402, C1403, C1601, C1602, C1604, C16112, C1646, C18, C1801, C1802, and C1803. [1420] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 595, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0214, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1421] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 596, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A3009, C0102, C0103, C0144, C0214, C0305, C0317, C0401, C0404, C0407, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0803, C1402, C1403, C1601, C1602, C16112, C1646, C18, C1801, C1802, and C1803. [1422] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 597, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2407, B1502, B1517, B1521, B1525, B1531, B3501, B3508, B4601, B5702, B5703, B5802, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0403, C0501, C0509, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0803, C0804, C0812, C1202, C1203, C1402, C1403, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. - 270 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1423] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 598, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, C0214, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C1402, and C1403. [1424] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 599, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2403, A2410, B1516, B1517, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0229, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [1425] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 600, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7404, C0303, C1602, and C1646. [1426] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 601, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A6602, A6603, A7404, B1516, B1517, B5201, B5702, B5703, B5802, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0403, C0501, C0509, C0602, C0704, C0705, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1427] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 602, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A6602, A6603, A7404, B1516, B1517, B5702, B5703, B5802, C0102, C0103, - 271 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0403, C0501, C0509, C0602, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1428] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 603, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A6602, A6603, A7404, B1516, B1517, B5702, B5703, B5802, C0102, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0705, C0801, C0803, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1429] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 604, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B4201, B4202, C0102, and C0144. [1430] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 605, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, C0303, C1202, and C1602. [1431] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 606, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, C0303, C1202, and C1602. - 272 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1432] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 607, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B4201, B4202, C0102, and C0144. [1433] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 608, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0204, A0205, A0207, A3401, A6602, A6603, A6802, A6827, A7404, B1302, B1303, B1516, B1517, B5201, B5702, B5703, B5802, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0403, C0501, C0509, C0602, C0704, C0705, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1434] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 609, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A7404, B1302, B1303, B5201, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0403, C0501, C0509, C0602, C0704, C0705, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1435] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 610, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B0801, B3503, B3508, B3910, B4201, B4202, B5501, B5502, B5601, B5604, B5610, B6701, B8101, B8103, B8201, B8202, C0102, and C0144. [1436] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 611, wherein a peptide with this - 273 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B4201, B4202, B5501, B5502, B5601, B5604, B5610, and B6701. [1437] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 612, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1516, B1517, B5702, B5703, B5802, C0202, C0210, C0217, C0229, C0302, C0303, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, and C1646. [1438] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 613, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A3401, A6602, A6603, A6802, A6827, A6901, A7404, B1302, B1303, B5201, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0403, C0501, C0509, C0602, C0704, C0705, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1439] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 614, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, C1602, and C1646. [1440] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 615, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5101, B5102, B5107, B5108, B5109, B5201, C0202, C0210, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. - 274 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1441] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 616, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402 and A6801. [1442] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 617, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0203, A02264, A3001, A3201, A6802, A6827, B1517, and C1502. [1443] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 618, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1444] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 619, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201 and B1517. [1445] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 620, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2901, A2902, A2911, A3002, A3009, B1501, B1502, B1503, B1512, B15220, B1525, B1527, and B1531. [1446] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 621, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1501, B1525, C1402, and C1403. - 275 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1447] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 622, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0109, A0201, A0202, A0211, A0230, A3601, A7404, C0501, and C0509. [1448] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 623, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1403, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, B7301, C0702, C0704, and C0705. [1449] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 624, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1518, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1450] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 625, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6802, A6827, A6901, B1302, B1303, B5101, B5102, B5107, B5108, B5109, B5201, C0202, C0210, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1451] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 626, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6802, A6827, B1302, B1303, B5101, B5102, B5107, B5108, B5109, B5201, C0202, C0210, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. - 276 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1452] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 627, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0202, C0210, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0801, C0803, C0804, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1453] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 628, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0203, A0204, A0205, A0206, A0211, A0214, A02264, A6802, A6827, A6901, B1302, B1303, B5107, B5201, C0704, C0801, C0803, C1203, C1502, C1505, C1601, C1602, C1604, C16112, C1701, C1702, C1703, C1704, and C1705. [1454] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 629, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0602 and C0704. [1455] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 630, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6802, A6827, B1302, B1303, B5101, B5102, B5107, B5108, B5109, B5201, C0202, C0210, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1456] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 631, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0109, A0123, A3601, A7404, C0501, and C0509. - 277 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1457] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 632, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0204, A0211, A02264, and B1302. [1458] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 633, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801, B2705, C1601, and C16112. [1459] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 634, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B0801, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3906, B3910, B4008, B4201, B4202, B5101, B5102, B5105, B5108, B5109, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B6701, B7801, B8101, B8103, B8201, B8202, C0801, and C0803. [1460] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 635, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B0801, B1401, B1402, B1502, B1508, B1511, B1518, B1521, B1525, B1531, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3910, B3924, B4008, B4201, B4202, B5101, B5102, B5105, B5107, B5108, B5109, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B6701, B7801, B8101, B8103, B8201, B8202, C0705, C0801, C0803, C1601, C1602, C1604, C16112, and C1646. [1461] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 636, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6901, B0702, B0705, B0801, B1401, B1402, B1403, B1502, B1508, B1510, B1511, - 278 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 B1531, B2705, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3901, B3906, B3910, B3924, B4008, B4201, B4202, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B6701, B7801, B8101, B8103, B8201, B8202, C0801, and C0803. [1462] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 637, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B1502, B1508, B1511, B1518, B1521, B1525, B1531, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3910, B4201, B4202, B5109, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B6701, C1601, C1602, C1604, C16112, and C1646. [1463] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 638, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, B0801, B1401, B1402, B1503, B15220, B2705, B2706, B2707, B5107, B5201, C0704, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C16112, and C1646. [1464] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 639, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001 and B2705. [1465] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 640, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1403, B1510, B1518, B1537, B2702, B2703, B2704, B2705, B2706, B2707, B3801, B3802, B3901, B3905, B3906, B3909, B3924, B7301, C0214, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1466] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 641, wherein a peptide with this - 279 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0204, A0211, A02264, and B1302. [1467] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 642, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1508, B1511, B1518, B1521, B1525, B1531, B2705, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B4701, B5101, B5108, B5109, B5201, B5301, B5604, B5610, C0102, C0144, C0303, C0304, C0305, C0317, C0704, C0705, C0801, C0803, C0804, C0812, C1505, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1468] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 643, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6901, B0702, B0801, B1401, B1402, B1403, B1502, B1508, B1510, B1511, B1521, B1525, B1531, B2705, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3910, B3924, B4201, B4202, B4701, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B6701, B7801, B8101, B8103, C0102, C0144, C0303, C0304, C0305, C0317, C0404, C0704, C0705, C0801, C0803, C0804, C0812, C1505, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1469] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 644, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, B0801, B1401, B1402, B1503, B15220, B2705, B2706, B2707, B5107, B5201, B5802, C0704, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C16112, and C1646. [1470] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 645, wherein a peptide with this - 280 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3910, B4201, B4202, B5101, B5102, B5105, B5108, B5109, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B6701, and B7801. [1471] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 646, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1403, B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, B3924, B7301, C0602, C0702, and C0704. [1472] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 647, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1403, B1510, B1518, B1537, B2702, B2703, B2704, B2705, B2706, B2707, B3801, B3802, B3901, B3905, B3906, B3909, B3924, B7301, C0214, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1473] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 648, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1403, B1510, B1518, B1537, B2702, B2703, B2704, B2705, B2706, B2707, B3801, B3802, B3901, B3905, B3906, B3909, B3924, B7301, C0214, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1474] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 649, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0204, A0205, A0211, A02264, and B1302. - 281 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1475] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 650, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0204, A0205, A0211, A02264, and B1302. [1476] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 651, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801. [1477] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 652, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801. [1478] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 653, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001 and B2705. [1479] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 654, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3201, B0801, B1302, B1303, B1517, B1525, B2705, B5107, B5201, B5703, B5802, C0202, C0210, C0214, C0229, C0302, C0303, C0305, C0317, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0803, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1480] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 655, wherein a peptide with this - 282 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1403, B1510, B1518, B1537, B2702, B2703, B2704, B2705, B2706, B2707, B3801, B3802, B3901, B3905, B3906, B3909, B3924, B7301, C0214, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1481] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 656, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1403, B1510, B1518, B1537, B2702, B2703, B2704, B2705, B2706, B2707, B3801, B3802, B3901, B3905, B3906, B3909, B3924, B7301, C0214, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1482] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 657, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B0801, B1401, B1402, B1403, B1502, B1508, B1511, B1521, B1531, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3906, B3910, B3924, B4008, B4201, B4202, B5101, B5102, B5105, B5107, B5108, B5109, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B6701, B7801, B8101, B8103, B8201, B8202, C0303, C0304, C0305, C0317, C0704, C0801, C0803, C1601, C1602, C16112, and C1646. [1483] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 658, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B1502, B1508, B1511, B1521, B1531, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B4201, B5301, B5501, B5502, B5601, B5604, B5610, B6701, C1601, C1602, C16112, and C1646. [1484] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 659, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 283 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of A3001, A3201, B0801, B1302, B1303, B1401, B1402, B1403, B1517, B1525, B2705, B2706, B2707, B5107, B5201, B5703, B5802, C0202, C0210, C0214, C0229, C0302, C0303, C0305, C0317, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0803, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1485] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 660, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3201, B0801, B1302, B1303, B1401, B1402, B1403, B1517, B1525, B2705, B2706, B2707, B5107, B5201, B5703, B5802, C0202, C0210, C0214, C0229, C0302, C0303, C0305, C0317, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0803, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1486] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 661, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3201, B0801, B1302, B1303, B1401, B1402, B1403, B1517, B1525, B2705, B2706, B2707, B5107, B5201, B5703, B5802, C0202, C0210, C0214, C0229, C0302, C0303, C0305, C0317, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C0801, C0803, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1487] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 662, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1508, B1511, B1521, B1531, B2705, B3501, B3503, B3505, B3508, B3532, B3541, B3543, B5101, B5107, B5108, B5109, B5201, B5301, B5604, B5610, C0102, C0144, C0303, C0304, C0305, C0317, C0704, C0705, C0801, C0803, C0804, C0812, C1505, C1601, C1602, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. - 284 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1488] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 663, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0801, B1401, B1402, B1403, B1502, B1510, B1511, B1521, B1531, B1537, B2705, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3910, B3924, B4201, B4202, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B6701, B7801, C0102, C0144, C0303, C0304, C0305, C0317, C0704, C0705, C0801, C0803, C0804, C0812, C1505, C1601, C1602, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1489] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 664, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1502, B1531, B3501, B3503, B3505, B3906, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B7801, C0102, C0144, C0303, C0304, C0305, C0317, C0704, C0705, C0801, C0803, C0804, C0812, C1505, C1601, C1602, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1490] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 665, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B0801, B1401, B1402, B1403, B1531, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3906, B3910, B3924, B4008, B4201, B4202, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B6701, B7801, B8101, B8103, B8201, B8202, C0801, and C0803. [1491] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 666, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, and A6801. - 285 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1492] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 667, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1493] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 668, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, and A6801. [1494] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 669, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0211, A02264, and A0230. [1495] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 670, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1496] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 671, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1497] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 672, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, A0206, A0214, A6802, A6827, A6901, and C1203. - 286 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1498] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 673, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, A0206, A0214, A6802, A6827, A6901, and C1203. [1499] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 674, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4501 and B4507. [1500] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 675, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3303, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1501] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 676, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2703, B2704, B2705, B2706, B2707, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1502] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 677, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2703, B2704, B2705, B2706, B2707, C0602, C0701, C0702, C0705, C0706, and C0718. [1503] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 678, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 287 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0205, A0206, A0214, A6802, A6827, A6901, B5401, B5502, and C1203. [1504] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 679, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C1203. [1505] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 680, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5401 and B5502. [1506] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R280K protein mutation comprises SEQ ID NO: 681, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A3101, A3104, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1507] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 682, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3401, A3402, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, and A7413. [1508] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 683, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3401, A3402, A6602, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, and A7413. - 288 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1509] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 684, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517 and B5801. [1510] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 685, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, A0206, A0211, A0214, A02264, A6802, A6827, and A6901. [1511] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 686, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1512] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 687, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3402, and A6801. [1513] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 688, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A2901, A2902, A2911, A3004, A3009, B1502, B1521, B1525, C0102, C0144, C0214, C0302, C0317, C0401, C0404, C0407, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C1203, C1402, C1403, C1601, C1602, C1604, C16112, and C1646. [1514] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 689, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 289 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A3004, A3009, C0102, C0144, C0214, C0401, C0404, C0407, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C1402, C1403, C1601, C1602, C16112, and C1646. [1515] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 690, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3009, A3201, B1516, B1517, B5701, B5703, B5704, B5801, B5802, C0202, C0210, C0217, C0229, C0302, C0303, C0304, C0317, C1202, C1203, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [1516] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 691, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3910, B4201, B5108, B5401, B5501, B5502, B5601, B5604, B5610, and B6701. [1517] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 692, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3401, A3402, A6602, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, and A7413. [1518] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 693, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0203, A0205, A0206, A0211, A0214, A02264, A6802, A6827, and A6901. [1519] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 694, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 290 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3004, A3009, B1502, B1521, B1525, C0102, C0144, C0214, C0302, C0303, C0305, C0317, C0404, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C1203, C1402, C1403, C1601, C1602, C1604, C16112, and C1646. [1520] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 695, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2901, A2902, A2911, A3004, A3009, B1502, B1521, B1525, C0214, C0302, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C1203, C1402, C1403, C1601, C1602, C1604, C16112, and C1646. [1521] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 696, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A3004, A3009, C0102, C0144, C0214, C0302, C0303, C0305, C0317, C0401, C0404, C0407, C0602, C0701, C0702, C0704, C0705, C0706, C0718, C1203, C1402, C1403, C1601, C1602, C1604, C16112, C1646, C1801, and C1802. [1522] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 697, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0204, A0205, B1516, B1517, B5201, B5702, B5703, B5802, C0102, C0144, C0202, C0210, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1523] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 698, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0204, A0205, A0206, A0211, A0214, and B5201. - 291 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1524] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 699, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1516, B1517, B5701, B5702, B5703, B5704, B5801, B5802, C1601, C1602, C16112, and C1646. [1525] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 700, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B3910, B4201, B5108, B5501, B5502, B5601, B5604, B5610, and B6701. [1526] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 701, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1527] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 702, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1528] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 703, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1529] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 704, wherein a peptide with this - 292 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0204, A0205, and A0211. [1530] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 705, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0202, A0204, A0205, and A0211. [1531] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 706, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2901, A2902, A2911, B1503, B15220, C1402, and C1403. [1532] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 707, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2410, A2901, A2902, A2911, B1503, B15220, C1402, and C1403. [1533] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 708, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2901, A2902, A2911, B1503, B15220, C1402, and C1403. [1534] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 709, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2901, A2902, A2911, B1503, B15220, C1402, and C1403. - 293 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1535] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 710, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2901, A2902, A2911, B1503, B15220, C1402, and C1403. [1536] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 711, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, A3305, A3401, A6601, A6602, and A6801. [1537] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 712, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, A3305, A3401, A6601, A6602, and A6801. [1538] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 713, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A2901, A2902, A2911, C0702, C1402, and C1403. [1539] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 714, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3104, A3303, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1540] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 715, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 294 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3303, A3401, A3402, A6602, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1541] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 716, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A2901, A2902, A2911, C0702, C1402, and C1403. [1542] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 717, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, C0702, C0705, C1402, and C1403. [1543] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 718, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, C1402, and C1403. [1544] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 719, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801. [1545] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 720, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1501, B1503, B15220, B1525, and B2705. [1546] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 721, wherein a peptide with this - 295 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3002, A3004, A3009, A3010, B1501, B1503, B15220, B1525, and B2705. [1547] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 722, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3002, A3004, A3009, A3010, B1501, B1503, B1517, B15220, B1525, and B2705. [1548] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 723, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001 and B0801. [1549] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 724, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B1518, B1521, B15220, B1525, and C0702. [1550] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 725, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0305, A3001, A3101, A3104, and A3303. [1551] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 726, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0305, A3001, A3101, A3104, and A3303. [1552] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 727, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 296 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001, A3101, A3104, A3303, B2702, B2704, and B2705. [1553] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 728, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0305, A3001, A3101, A3104, and A3303. [1554] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 729, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, and A6801. [1555] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 730, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001 and B0801. [1556] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 731, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1557] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 732, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3101, A3104, A3401, A3402, A3601, A6602, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1558] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 733, wherein a peptide with this - 297 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3401, A6602, A6603, A7404, and C1602. [1559] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 734, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A1101, A1102, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A7404, and C1602. [1560] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 735, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, A7413, and C1602. [1561] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 736, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1401, B1402, B1403, B3906, and B3924. [1562] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 737, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B1521, B15220, and B1525. [1563] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 738, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B3503, B4201, B4202, B5501, B5502, B5601, B5604, B5610, and B6701. - 298 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1564] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 739, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4002, B4006, B40114, B4101, B4102, B4415, B4501, B4507, and B5001. [1565] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 740, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B4002, B4006, B40114, B4101, B4102, B4415, B4501, B4507, and B5001. [1566] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 741, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, and A7405. [1567] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 742, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, and A7405. [1568] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 743, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, and A3305. [1569] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 744, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5401 and B5502. - 299 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1570] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 745, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6802 and A6827. [1571] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 746, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6802 and A6827. [1572] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 747, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1573] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 748, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3001. [1574] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 749, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2703, B2704, B2705, B2706, B2707, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1575] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 750, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 300 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of B2702, B2703, B2704, B2705, B2706, B2707, C0602, C0701, C0702, C0704, C0705, C0706, and C0718. [1576] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 751, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B2702, B2703, B2704, B2705, B2706, B2707, C0602, C0701, C0702, C0705, C0706, and C0718. [1577] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 752, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, and A7405. [1578] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 753, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5401 and B5502. [1579] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 754, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6802 and A6827. [1580] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 755, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1581] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 756, wherein a peptide with this - 301 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0203, A0205, and A02264. [1582] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 757, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0203, A0205, and A02264. [1583] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 758, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, and B1525. [1584] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 759, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B15220, B1525, and C1202. [1585] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 760, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1503, B1517, B15220, B1525, C0302, C1202, C1601, C1602, C16112, and C1646. [1586] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 761, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1587] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 762, wherein a peptide with this - 302 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1588] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 763, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0305, A1101, A1102, A3001, and A3402. [1589] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 764, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0305, A1101, A1102, A3001, and A3402. [1590] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 765, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1525, C0102, C0144, C0202, C0210, C0229, C0302, C0303, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1591] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 766, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1502, B1525, C0202, C0210, C0229, C0302, C1202, C1504, C1509, C1601, C1602, C16112, and C1646. [1592] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 767, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 303 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1502, B1525, C0202, C0210, C0229, C1202, C1504, C1509, C1601, and C16112. [1593] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 768, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0302, C1202, C1203, C1601, C1604, and C16112. [1594] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 769, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402, C0302, C1202, C1203, C1601, C1604, and C16112. [1595] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 770, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402. [1596] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 771, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3402. [1597] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 772, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1598] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 773, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 304 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A3101, A3104, A3301, A3303, A3305, A3401, A3402, A3601, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1599] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 774, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601 and C0303. [1600] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 775, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0401, C0403, C0404, C0407, C0501, C0509, C0704, C0705, C0801, C0802, C0803, C0812, C1601, C1602, C16112, C1646, C1801, and C1802. [1601] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 776, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0401, C0403, C0404, C0407, C0501, C0509, C0704, C0801, C0802, C0803, C0812, C1601, C1602, C16112, C1646, C1801, and C1802. [1602] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 777, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C0401, C0403, C0404, C0407, C0501, C0509, C0704, C0801, C0802, C0803, C0812, C1601, C1602, C16112, C1646, C1801, and C1802. [1603] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 778, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 305 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of C0401, C0403, C0404, C0407, C0501, C0509, C0704, C0705, C0801, C0802, C0803, C0812, C1601, C1602, C16112, C1646, C1801, and C1802. [1604] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 779, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801, B1401, B1402, B1403, B4202, and C0704. [1605] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 780, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801, B1401, B1402, B1403, B4202, and C0704. [1606] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 781, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0801, B1401, B1402, B1403, and C0704. [1607] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 782, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, B5701, B5702, B5703, and B5704. [1608] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 783, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3601, B5701, B5702, B5703, B5704, and B5802. [1609] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 784, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 306 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of C1402 and C1403. [1610] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 785, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C1402 and C1403. [1611] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 786, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C1402 and C1403. [1612] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 787, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C1402 and C1403. [1613] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 788, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of C1402 and C1403. [1614] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 789, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5703, B5802, C1602, and C1646. [1615] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 790, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 307 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5703 and B5802. [1616] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 791, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B5703 and B5802. [1617] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 792, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, and A3601. [1618] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 793, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, and A3601. [1619] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 794, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2902, and A2911. [1620] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 795, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1621] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 796, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 308 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1510, B1518, B1537, B3801, B3802, B3901, B3905, B3906, B3909, and B3924. [1622] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 797, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A2603, A2630, A3001, A3004, A3009, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1504, C1509, C1602, and C1646. [1623] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 798, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3002, A3004, A3009, A3010, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7410, A7411, A7413, C0202, C0210, C0214, C0229, C0302, C0303, C1202, C1504, C1509, C1601, C1602, C1604, C16112, and C1646. [1624] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 799, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, C0202, C0210, C0229, C0303, C1202, C1504, C1509, C1602, and C1646. [1625] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 800, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0204, A0205, B1301, B1302, B1303, B1502, B1525, B2705, B3503, B4201, B4701, - 309 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 B5108, B5201, B5604, B5610, B5703, B5802, C0102, C0103, C0144, C0202, C0210, C0214, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0501, C0509, C0602, C0704, C0705, C0801, C0802, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1626] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 801, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3303, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0303, C1202, C1504, C1509, C1601, C1602, C16112, and C1646. [1627] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 802, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1628] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 803, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1629] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 804, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0211, A02264, A0230, B0702, B0705, B3503, B3910, B4201, B4202, B5108, B5501, B5502, B5601, B5604, B5610, B6701, B8101, and B8103. - 310 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1630] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 805, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1301, B1802, B3701, B4002, B40114, B4102, B4402, B4403, B4404, B4405, B4407, B4427, B4901, B5701, B5703, B5704, and B5802. [1631] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 806, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B3501, B3502, B3503, B3508, B3512, B3541, B3910, B4201, B4202, B5105, B5108, B5109, B5501, B5502, B5601, B5604, B5610, B6701, B8101, and B8103. [1632] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 807, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B0801, B1403, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3910, B4008, B4201, B4202, B5101, B5102, B5105, B5108, B5109, B5301, B5501, B5502, B5601, B5604, B5610, B6701, B8101, B8103, B8201, B8202, C0801, and C0803. [1633] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 808, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3201, B1516, B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1634] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 809, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0102, A2403, A2410, A2901, A2902, A2911, A3001, A3002, A3004, A3009, A3010, A3201, A3601, A7404, A7405, A7410, B1301, B1501, B1502, B1503, B1516, B1517, B15220, B1524, B1525, B1531, B5701, B5702, B5703, B5704, B5801, B5802, C0202, C0210, C0214, - 311 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 C0229, C0302, C0701, C0705, C0706, C0718, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, and C1646. [1635] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 810, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, and A7413. [1636] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 811, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, A7404, B1302, B1303, and B5201. [1637] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 812, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1638] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 813, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B1517, B5701, B5702, B5703, B5704, B5801, and B5802. [1639] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 814, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, and A6801. - 312 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1640] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 815, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1641] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 816, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3301, A3303, A3305, A3401, and A6801. [1642] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 817, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3004, A3009, A3101, A3104, A3402, A3601, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, A7413, and B2705. [1643] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 E285K protein mutation comprises SEQ ID NO: 818, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1644] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 819, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, and A6801. [1645] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 820, wherein a peptide with this - 313 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1646] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 821, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0201, A0202, A0203, A0204, A0205, A0206, A0207, A0211, A0214, A02264, A0230, and B1302. [1647] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 822, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A2901, A2902, A2911, A3009, B5702, C0214, C0401, C0404, C0407, C0702, C0704, C0705, C1402, and C1403. [1648] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 823, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3104, A7401, A7402, A7403, A7404, A7405, A7408, A7409, A7411, and A7413. [1649] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 824, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2301, A2402, A2403, A2407, A2410, A2464, A2901, A2902, A2911, A3004, A3009, B5702, C0214, C0401, C0404, C0407, C0702, C0704, C0705, C1402, C1403, C1602, and C1646. [1650] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 825, wherein a peptide with this - 314 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B0801, B3501, B3503, B3505, B3508, B3910, B4201, B4202, B5501, B5502, B5601, B5604, B5610, B6701, B8101, B8103, B8201, B8202, C0102, and C0144. [1651] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 826, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0302, A1101, A1102, A3101, A3104, A3301, A3303, A3305, A3401, A3402, A3601, A6601, A6602, A6603, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, A7413, C0303, C1202, and C1602. [1652] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 827, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0203, A0204, A0205, A0206, A0211, A0214, A02264, A6802, A6827, A6901, B1302, B1303, B5101, B5102, B5107, B5108, B5109, B5201, C0202, C0210, C0217, C0229, C0302, C0303, C0304, C0305, C0317, C0602, C0704, C0801, C0803, C0804, C0812, C1202, C1203, C1502, C1504, C1505, C1509, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, C1706, and C1707. [1653] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 828, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A2901, A2902, A2911, A3002, A3009, B1501, B1502, B1503, B1512, B15220, B1525, B1527, B1531, C1402, and C1403. [1654] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 829, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A6901, B0702, B0705, B0801, B1401, B1402, B1403, B1502, B1508, B1510, B1511, B1518, B1521, B1525, B1531, B1537, B2705, B3501, B3502, B3503, B3505, B3508, B3512, - 315 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 B3532, B3541, B3543, B3901, B3905, B3906, B3909, B3910, B3924, B4008, B4201, B4202, B4701, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B6701, B7801, B8101, B8103, B8201, B8202, C0102, C0144, C0303, C0304, C0305, C0317, C0404, C0704, C0705, C0801, C0803, C0804, C0812, C1505, C1601, C1602, C1604, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1655] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 830, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of B0702, B0705, B0801, B1401, B1402, B1403, B1502, B1508, B1510, B1511, B1521, B1531, B1537, B2705, B3501, B3502, B3503, B3505, B3508, B3512, B3532, B3541, B3543, B3901, B3906, B3909, B3910, B3924, B4008, B4201, B4202, B5101, B5102, B5105, B5107, B5108, B5109, B5201, B5301, B5401, B5501, B5502, B5601, B5604, B5610, B6701, B7801, B8101, B8103, B8201, B8202, C0102, C0144, C0303, C0304, C0305, C0317, C0704, C0705, C0801, C0803, C0804, C0812, C1505, C1601, C1602, C16112, C1646, C17, C1701, C1702, C1703, C1704, C1705, and C1706. [1656] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 831, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A3101, A3104, A3301, A3303, A3305, A3401, A3402, A6601, A6602, A6603, A6801, A7401, A7402, A7403, A7404, A7405, A7408, A7409, and A7411. [1657] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 832, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3401, A3402, A6602, A6801, A74, A7401, A7402, A7403, A7404, A7405, A7406, A7407, A7408, A7409, A7411, and A7413. [1658] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 833, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 316 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0301, A0302, A0305, A1101, A1102, A3001, A3101, A3104, A3402, A74, A7401, A7402, A7403, A7404, A7405, A7407, A7408, A7409, A7411, and A7413. [1659] In some embodiments, the amino acid sequence for an MHC class I peptide vaccine for a TP53 Y234C protein mutation comprises SEQ ID NO: 834, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of A0101, A0102, A0103, A0109, A0123, and A3601. [1660] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 835, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0701, DRB1_0901, DRB1_1001, DPA10103-DPB10601, DPA10103- DPB15001, DPA10105-DPB15001, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. [1661] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 836, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0701, DRB1_0901, DRB1_1001, DPA10103-DPB10301, DPA10103- DPB10601, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103-DPB15001, DPA10104-DPB10301, DPA10105- DPB10301, DPA10105-DPB15001, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. [1662] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 837, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0701, DRB1_0901, DRB1_1001, DPA10103-DPB10301, DPA10103- DPB10601, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103-DPB15001, DPA10104-DPB10301, DPA10105- - 317 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPB10301, DPA10105-DPB15001, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. [1663] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 838, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0701, DRB1_0901, DRB1_1001, DPA10103-DPB15001, DPA10105- DPB15001, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. [1664] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 839, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DPA10103-DPB10301, DPA10103-DPB10601, DPA10103- DPB112401, DPA10103-DPB11401, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103-DPB15001, DPA10104-DPB10301, DPA10105-DPB10301, DPA10105- DPB15001, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. [1665] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 840, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0701, DPA10103-DPB10301, DPA10103-DPB10601, DPA10103- DPB112401, DPA10103-DPB11401, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103-DPB15001, DPA10104-DPB10301, DPA10105-DPB10301, DPA10105- DPB15001, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. [1666] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 841, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10301, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103- - 318 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPB15001, DPA10104-DPB10301, DPA10105-DPB10301, DPA10105-DPB15001, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11401, DQA10102- DQB10601, DQA10103-DQB10601, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, and DQA10506-DQB10303. [1667] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 842, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10301-DQB10301, DQA10302- DQB10301, DQA10303-DQB10301, and DQA10506-DQB10303. [1668] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 843, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10401-DPB10301, DPA10401-DPB11401, DQA10102-DQB10601, DQA10103- DQB10601, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, and DQA10506-DQB10303. [1669] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a BRAF G466V protein mutation comprises SEQ ID NO: 844, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB15001, DPA10105-DPB15001, DPA10401-DPB10301, DPA10401- DPB11401, DQA10102-DQB10601, DQA10103-DQB10601, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, and DQA10506-DQB10303. [1670] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 845, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102- DQB10602, DQA10103-DQB10601, DQA10201-DQB10301, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10501-DQB10301, DQA10501- DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, - 319 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQA10505-DQB10319, DQA10505-DQB10402, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1671] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 846, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102- DQB10602, DQA10103-DQB10601, DQA10201-DQB10301, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10501-DQB10301, DQA10501- DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1672] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 847, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501, DQA10102-DQB10601, DQA10102-DQB10602, DQA10103- DQB10601, DQA10201-DQB10301, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503- DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601- DQB10301. [1673] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 848, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102- DQB10602, DQA10103-DQB10601, DQA10201-DQB10301, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10501-DQB10301, DQA10501- DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. - 320 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1674] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 849, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DQA10102-DQB10501, DQA10102-DQB10601, DQA10103- DQB10601, DQA10201-DQB10301, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503- DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601- DQB10301. [1675] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 850, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301- DPB10201, DPA10301-DPB10202, DPA10301-DPB11801, DPA10301-DPB14001, and DPA10401-DPB10101. [1676] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 851, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301-DPB10201, and DPA10301-DPB11801. [1677] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 852, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB11801, DPA10301- DPB14001, and DPA10401-DPB10101. [1678] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 853, wherein a peptide with this - 321 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DQA10102-DQB10601, DQA10102-DQB10602, DQA10103- DQB10601, DQA10103-DQB10602, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10501-DQB10301, DQA10501- DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508- DQB10301, and DQA10509-DQB10301. [1679] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 D32G protein mutation comprises SEQ ID NO: 854, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DQA10102-DQB10601, DQA10102-DQB10602, DQA10103- DQB10601, DQA10103-DQB10602, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10501-DQB10301, DQA10501- DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508- DQB10301, and DQA10509-DQB10301. [1680] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 855, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10502, DQA10102- DQB10503, DQA10103-DQB10501, DQA10104-DQB10501, and DQA10105-DQB10501. [1681] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 856, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10104-DQB10501, and DQA10105- DQB10501. [1682] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 857, wherein a peptide with this - 322 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10502, DQA10102- DQB10503, DQA10103-DQB10501, DQA10104-DQB10501, and DQA10105-DQB10501. [1683] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 858, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10503, DQA10104- DQB10501, and DQA10105-DQB10501. [1684] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 859, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10503, DQA10104- DQB10501, and DQA10105-DQB10501. [1685] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 860, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10503, DQA10104- DQB10501, and DQA10105-DQB10501. [1686] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 861, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10503, DQA10104- DQB10501, and DQA10105-DQB10501. [1687] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 862, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 323 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10503, DQA10104- DQB10501, and DQA10105-DQB10501. [1688] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 863, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10503, DQA10104- DQB10501, and DQA10105-DQB10501. [1689] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 G34E protein mutation comprises SEQ ID NO: 864, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10503, DQA10104- DQB10501, and DQA10105-DQB10501. [1690] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S33C protein mutation comprises SEQ ID NO: 865, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1691] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 866, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10502, DQA10102- DQB10503, DQA10103-DQB10501, DQA10103-DQB10503, DQA10104-DQB10501, and DQA10105-DQB10501. [1692] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 867, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 324 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10502, DQA10102- DQB10503, DQA10103-DQB10501, DQA10103-DQB10503, DQA10104-DQB10501, and DQA10105-DQB10501. [1693] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 868, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10502, DQA10102- DQB10503, DQA10103-DQB10501, DQA10103-DQB10503, DQA10104-DQB10501, and DQA10105-DQB10501. [1694] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 869, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501, DQA10102-DQB10503, and DQA10103-DQB10501. [1695] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 870, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501 and DQA10103-DQB10501. [1696] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 871, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10502, DQA10102- DQB10503, DQA10103-DQB10501, DQA10103-DQB10503, DQA10104-DQB10501, and DQA10105-DQB10501. [1697] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 872, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 325 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10502, DQA10102- DQB10503, DQA10103-DQB10501, DQA10103-DQB10503, DQA10104-DQB10501, and DQA10105-DQB10501. [1698] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 873, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10501, DQA10102-DQB10501, DQA10102-DQB10502, DQA10102- DQB10503, DQA10103-DQB10501, DQA10103-DQB10503, DQA10104-DQB10501, and DQA10105-DQB10501. [1699] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 874, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501 and DQA10103-DQB10501. [1700] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S33F protein mutation comprises SEQ ID NO: 875, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501 and DQA10103-DQB10501. [1701] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 876, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302- DQB10301, DQA10303-DQB10301, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505- DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1702] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 877, wherein a peptide with this - 326 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302- DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505- DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1703] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 878, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302- DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505- DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1704] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 879, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302- DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505- DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1705] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 880, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10303, DQA10401-DQB10301, DQA10401- DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, - 327 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506- DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1706] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 881, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302- DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505- DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1707] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 882, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302- DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505- DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1708] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 883, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303- DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505- DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1709] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 884, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 328 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302- DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505- DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1710] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37C protein mutation comprises SEQ ID NO: 885, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302- DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505- DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1711] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 886, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0404, and DQA10505-DQB10402. [1712] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 887, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0404 and DQA10505-DQB10402. [1713] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 888, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601 and DQA10103-DQB10602. - 329 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1714] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 889, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10304, DQA10302-DQB10304, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401- DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, and DQA10601-DQB10301. [1715] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 890, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302-DQB10304, DQA10303- DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505- DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601- DQB10301. [1716] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 891, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0408, DRB1_0901, DRB1_1001, DQA10102-DQB10501, DQA10102-DQB10601, DQA10103-DQB10501, DQA10103-DQB10609, DQA10201- DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506- DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1717] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 892, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 330 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0408, DRB1_1001, DQA10102-DQB10501, and DQA10103-DQB10501. [1718] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 893, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0408, DRB1_0901, DRB1_1001, DQA10102-DQB10501, DQA10102-DQB10601, DQA10103-DQB10501, DQA10103-DQB10609, DQA10201- DQB10301, DQA10201-DQB10303, DQA10505-DQB10402, DQA10506-DQB10303, and DQA10601-DQB10301. [1719] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 894, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0901, DQA10102-DQB10501, DQA10103-DQB10501, DQA10103- DQB10609, DQA10505-DQB10402, and DQA10506-DQB10303. [1720] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S37F protein mutation comprises SEQ ID NO: 895, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DQA10102-DQB10501, DQA10102-DQB10601, DQA10103- DQB10501, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10303, and DQA10506-DQB10303. [1721] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 896, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10201-DQB10302, DQA10201- DQB10303, DQA10505-DQB10302, and DQA10506-DQB10303. - 331 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1722] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 897, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201- DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508- DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1723] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 898, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10303, DQA10401-DQB10301, DQA10401- DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506- DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1724] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 899, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201- DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508- DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1725] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 900, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 332 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DQA10102-DQB10601, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201- DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508- DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1726] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 901, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201- DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508- DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1727] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 902, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201- DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508- DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1728] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 903, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201- DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, - 333 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508- DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1729] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 904, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201- DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508- DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1730] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45F protein mutation comprises SEQ ID NO: 905, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201- DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508- DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1731] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 906, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301 and DQA10601-DQB10301. [1732] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 907, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 334 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10103-DQB10601, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301- DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503- DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601- DQB10301. [1733] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 908, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302- DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505- DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1734] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 909, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10201-DQB10301, DQA10201- DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501- DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1735] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 910, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10201-DQB10301, DQA10201- DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, - 335 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501- DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1736] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 911, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10201-DQB10301, DQA10201- DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501- DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1737] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 912, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10201-DQB10301, DQA10201- DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10506-DQB10303, and DQA10601- DQB10301. [1738] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 913, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10103-DQB10601, DQA10201-DQB10301, DQA10201- DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501- DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. - 336 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1739] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 914, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10103-DQB10601, DQA10201-DQB10303, and DQA10506-DQB10303. [1740] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 S45P protein mutation comprises SEQ ID NO: 915, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601 and DQA10103-DQB10601. [1741] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 916, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102-DQB10602, DQA10103-DQB10602, DQA10103-DQB10609, DQA10201- DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303- DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505- DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1742] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 917, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10611, DQA10103-DQB10602, DQA10103- DQB10609, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302-DQB10304, DQA10303- DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505- - 337 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601- DQB10301. [1743] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 918, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10611, DQA10103-DQB10601, DQA10103- DQB10602, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302- DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503- DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1744] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 919, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10611, DQA10103-DQB10601, DQA10103- DQB10602, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302- DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503- DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1745] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 920, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 338 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10611, DQA10103-DQB10601, DQA10103- DQB10602, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302- DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503- DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1746] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 921, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10611, DQA10103-DQB10601, DQA10103- DQB10602, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302- DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503- DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1747] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 922, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10611, DQA10103-DQB10601, DQA10103- DQB10602, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302- DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, - 339 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503- DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1748] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 923, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102- DQB10602, DQA10102-DQB10611, DQA10103-DQB10601, DQA10103-DQB10602, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301- DQB10301, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401- DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505- DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1749] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 924, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DQA10101-DQB10601, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10611, DQA10103-DQB10601, DQA10103- DQB10602, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302- DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503- DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1750] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41A protein mutation comprises SEQ ID NO: 925, wherein a peptide with this - 340 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10301- DQB10301, DQA10301-DQB10303, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302-DQB10303, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303- DQB10303, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505- DQB10301, DQA10505-DQB10302, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601- DQB10301. [1751] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 926, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_1001, DQA10101-DQB10601, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103- DQB10601, DQA10103-DQB10602, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301- DQB10304, DQA10302-DQB10301, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10302, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505- DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1752] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 927, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_1001, DQA10101-DQB10601, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103- DQB10601, DQA10103-DQB10602, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301- - 341 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQB10304, DQA10302-DQB10301, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10302, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505- DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1753] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 928, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_1001, DQA10101-DQB10601, DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103- DQB10601, DQA10103-DQB10602, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301- DQB10304, DQA10302-DQB10301, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10302, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505- DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1754] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 929, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0404, DRB1_0901, DRB1_1001, DQA10505-DQB10402, and DQA10506-DQB10303. [1755] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 930, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_0901, DRB1_1001, DQA10201-DQB10303, DQA10505-DQB10402, and DQA10506-DQB10303. - 342 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1756] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 931, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_0901, DRB1_1001, DQA10102-DQB10601, DQA10103-DQB10601, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201- DQB10303, DQA10301-DQB10301, DQA10301-DQB10304, DQA10302-DQB10301, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401- DQB10301, DQA10401-DQB10319, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10302, DQA10505- DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1757] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 932, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_1001, and DQA10505-DQB10402. [1758] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 933, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DQA10102-DQB10501, DQA10102-DQB10609, DQA10103- DQB10609, DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10304, DQA10302-DQB10304, DQA10303-DQB10304, DQA10501-DQB10301, DQA10501- DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506-DQB10303, DQA10508- DQB10301, and DQA10509-DQB10301. [1759] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 934, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DQA10102-DQB10501, DQA10102-DQB10609, DQA10103-DQB10609, - 343 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQA10201-DQB10301, DQA10201-DQB10303, DQA10301-DQB10301, DQA10301- DQB10304, DQA10302-DQB10301, DQA10302-DQB10304, DQA10303-DQB10301, DQA10303-DQB10304, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10505-DQB10402, DQA10506- DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1760] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a CTNNB1 T41I protein mutation comprises SEQ ID NO: 935, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DQA10102-DQB10501, DQA10102-DQB10609, DQA10103- DQB10609, DQA10201-DQB10303, DQA10505-DQB10402, and DQA10506-DQB10303. [1761] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 936, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1402, and DRB1_1406. [1762] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 937, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1103, DRB1_1104, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1402, and DRB1_1406. [1763] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 938, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1402, and DRB1_1406. - 344 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1764] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 939, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0301, DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1402, and DRB1_1406. [1765] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 940, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1402, and DRB1_1406. [1766] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 941, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0301. [1767] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 942, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1402, and DRB1_1406. [1768] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 943, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, and DPA10401-DPB10202. - 345 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1769] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 944, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB13401, DPA10301-DPB11801, and DPA10301-DPB14001. [1770] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146T protein mutation comprises SEQ ID NO: 945, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1114 and DRB1_1302. [1771] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 946, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0301. [1772] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 947, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1402, and DRB1_1406. [1773] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 948, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1402, and DRB1_1406. [1774] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 949, wherein a peptide with this - 346 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1301, DRB1_1304, DRB1_1402, and DRB1_1406. [1775] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 950, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1402, and DRB1_1406. [1776] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 951, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1114 and DRB1_1302. [1777] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 952, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101 and DRB1_0102. [1778] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 953, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101. [1779] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 954, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0102. - 347 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1780] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS A146V protein mutation comprises SEQ ID NO: 955, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, and DRB1_1406. [1781] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 956, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1782] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 957, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1783] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 958, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1784] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 959, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1785] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 960, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. - 348 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1786] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 961, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1787] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 962, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1788] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 963, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1789] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 964, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1790] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a KRAS Q61H protein mutation comprises SEQ ID NO: 965, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1791] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 966, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DRB1_1304, DPA10103-DPB11501, DPA10104-DPB11501, - 349 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB11801, DPA10401- DPB10101, DPA10401-DPB10201, and DPA10401-DPB10202. [1792] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 967, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DRB1_1304, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB11801, DPA10401- DPB10101, DPA10401-DPB10201, and DPA10401-DPB10202. [1793] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 968, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001, DRB1_1304, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301- DPB10201, DPA10301-DPB10202, DPA10301-DPB11801, DPA10401-DPB10101, DPA10401-DPB10201, and DPA10401-DPB10202. [1794] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 969, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DRB1_1304, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB11801, DPA10401- DPB10101, DPA10401-DPB10201, and DPA10401-DPB10202. [1795] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 970, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DRB1_1304, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB11801, and DPA10401- DPB10101. - 350 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1796] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 971, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DRB1_1304, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB11801, DPA10401- DPB10101, DPA10401-DPB10201, and DPA10401-DPB10202. [1797] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 972, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DRB1_1304, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10201, and DPA10301-DPB11801. [1798] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 973, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, and DRB1_1304. [1799] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 974, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10202-DPB110601 and DPA10202-DPB11901. [1800] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA C420R protein mutation comprises SEQ ID NO: 975, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10401, DPA10301- DPB12301, DPA10301-DPB13901, and DPA10301-DPB14001. [1801] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 976, wherein a peptide with this - 351 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1802] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 977, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1103, DRB1_1104, and DRB1_1304. [1803] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 978, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, and DQA10102-DQB10501. [1804] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 979, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, and DQA10102-DQB10501. [1805] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 980, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, and DRB1_1001. [1806] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 981, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 352 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, and DQA10102-DQB10501. [1807] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 982, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, and DQA10102-DQB10501. [1808] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 983, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, and DQA10102-DQB10501. [1809] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 984, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, and DQA10102-DQB10501. [1810] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E453K protein mutation comprises SEQ ID NO: 985, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_1001, and DQA10102-DQB10501. [1811] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 986, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10301-DPB11801, DPA10301-DPB14001, and DQA10102-DQB10501. - 353 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1812] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 987, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1501, DPA10301-DPB11801, and DQA10102-DQB10501. [1813] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 988, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1501, DPA10301-DPB11801, DPA10301-DPB14001, and DQA10102-DQB10501. [1814] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 989, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, and DPA10301-DPB14001. [1815] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 990, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB11801, and DPA10301- DPB14001. [1816] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 991, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, and DPA10301-DPB14001. [1817] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 992, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 354 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB11801, and DPA10301- DPB14001. [1818] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 993, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1304, DPA10301-DPB11801, DPA10301-DPB14001, and DQA10102-DQB10501. [1819] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 994, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [1820] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E545A protein mutation comprises SEQ ID NO: 995, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10301-DPB10101 and DPA10401-DPB10101. [1821] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 996, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0806, DRB1_1102, DRB1_1104, DRB1_1301, and DRB1_1406. [1822] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 997, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0806, DRB1_1102, DRB1_1104, DRB1_1301, and DRB1_1406. [1823] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 998, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 355 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0806, DRB1_1102, DRB1_1104, DRB1_1301, and DRB1_1406. [1824] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 999, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0404, DRB1_0804, DRB1_0806, DRB1_1304, DRB1_1406, DPA10202-DPB10501, and DPA10202-DPB13801. [1825] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 1000, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB13101, DPA10202-DPB10101, DPA10202-DPB10501, DPA10202- DPB13101, DPA10202-DPB13801, DPA10301-DPB10401, DPA10301-DPB12301, DPA10301-DPB13901, DPA10401-DPB10101, and DPA10401-DPB10501. [1826] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 1001, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10106-DPB10101, DPA10201-DPB10101, DPA10202-DPB10101, DPA10202- DPB13101, DPA10301-DPB10402, DPA10301-DPB110501, DPA10301-DPB14901, and DPA10301-DPB18001. [1827] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 1002, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10106-DPB10101, DPA10201-DPB10101, DPA10202-DPB10101, DPA10202- DPB10501, DPA10202-DPB13101, DPA10202-DPB13801, DPA10301-DPB10402, DPA10301-DPB110501, DPA10301-DPB11801, DPA10301-DPB14901, and DPA10301- DPB18001. - 356 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1828] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 1003, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0806, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, and DRB1_1304. [1829] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 1004, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0806, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, and DRB1_1304. [1830] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA E726K protein mutation comprises SEQ ID NO: 1005, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001. [1831] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 1006, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0405, DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1501, DRB1_1502, DRB1_1602, DPA10103-DPB11501, DPA10104-DPB11501, DPA10202-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301- DPB11801, DQA10102-DQB10501, DQA10102-DQB10503, DQA10102-DQB10604, DQA10102-DQB10609, DQA10103-DQB10501, DQA10103-DQB10609, and DQA10201- DQB10301. [1832] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 1007, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1304, DPA10103-DPB10101, DPA10103-DPB11501, DPA10103-DPB15001, DPA10104-DPB10101, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105- DPB15001, DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB10201, - 357 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPA10301-DPB10202, DPA10301-DPB10401, DPA10301-DPB110601, DPA10301- DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB16501, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401- DPB10202, and DQA10102-DQB10609. [1833] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 1008, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0408, DRB1_0410, DRB1_0701, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1401, DRB1_1404, DRB1_1406, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10103- DPB15001, DPA10104-DPB11501, DPA10105-DPB15001, DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301- DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB16501, DPA10401- DPB10201, DPA10401-DPB10202, DQA10102-DQB10501, DQA10102-DQB10503, DQA10102-DQB10604, DQA10102-DQB10609, DQA10103-DQB10501, DQA10103- DQB10609, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10501-DQB10203, and DQA10506-DQB10303. [1834] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 1009, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0408, DRB1_0410, DRB1_0701, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1401, DRB1_1404, DRB1_1406, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10103- DPB15001, DPA10104-DPB11501, DPA10105-DPB15001, DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301- DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB16501, DPA10401- - 358 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPB10201, DPA10401-DPB10202, DQA10102-DQB10501, DQA10102-DQB10503, DQA10102-DQB10601, DQA10102-DQB10604, DQA10102-DQB10609, DQA10102- DQB10611, DQA10103-DQB10501, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10401- DQB10301, DQA10401-DQB10319, DQA10501-DQB10203, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10301, DQA10505- DQB10302, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601-DQB10301. [1835] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 1010, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0408, DRB1_0410, DRB1_0701, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1401, DRB1_1404, DRB1_1406, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10104- DPB11501, DPA10202-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB14001, DPA10401- DPB10201, DPA10401-DPB10202, DQA10102-DQB10501, DQA10102-DQB10503, DQA10102-DQB10604, DQA10102-DQB10609, DQA10103-DQB10501, DQA10103- DQB10609, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10501-DQB10203, DQA10505-DQB10302, and DQA10506-DQB10303. [1836] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 1011, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0408, DRB1_0410, DRB1_0701, DRB1_0901, DRB1_1001, DPA10301-DPB10101, DPA10401-DPB10101, DPA10401-DPB11401, DQA10102-DQB10501, DQA10102-DQB10503, DQA10102- DQB10601, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103-DQB10501, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201- DQB10302, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302-DQB10301, - 359 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501- DQB10201, DQA10501-DQB10203, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10201, DQA10505-DQB10202, DQA10505- DQB10301, DQA10505-DQB10302, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509-DQB10301, and DQA10601- DQB10301. [1837] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 1012, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0408, DRB1_0410, DRB1_0701, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1401, DRB1_1404, DRB1_1406, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1602, DPA10103-DPB10101, DPA10103-DPB11501, DPA10103- DPB15001, DPA10104-DPB10101, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105-DPB15001, DPA10202-DPB10101, DPA10301-DPB10101, DPA10301- DPB10201, DPA10301-DPB10202, DPA10301-DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301- DPB14001, DPA10301-DPB16501, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB11401, DQA10102-DQB10501, DQA10102- DQB10503, DQA10102-DQB10601, DQA10102-DQB10604, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103-DQB10501, DQA10103-DQB10601, DQA10103- DQB10609, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10201, DQA10501- DQB10203, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503-DQB10301, DQA10505-DQB10201, DQA10505-DQB10202, DQA10505-DQB10301, DQA10505- DQB10302, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, and DQA10509-DQB10301. [1838] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 1013, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 360 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0410, DRB1_0701, DRB1_0813, DRB1_0901, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1401, DRB1_1404, DRB1_1406, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1602, DPA10103-DPB10101, DPA10103-DPB11501, DPA10103-DPB15001, DPA10104- DPB10101, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105-DPB15001, DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301- DPB16501, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DQA10102-DQB10501, DQA10102-DQB10503, DQA10102-DQB10601, DQA10102- DQB10604, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103-DQB10501, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201- DQB10303, DQA10501-DQB10201, DQA10501-DQB10203, DQA10505-DQB10201, DQA10505-DQB10202, DQA10505-DQB10302, and DQA10506-DQB10303. [1839] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 1014, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_0410, DRB1_0701, DRB1_0901, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1401, DRB1_1404, DRB1_1406, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10104-DPB11501, DPA10202-DPB10101, DPA10301- DPB10201, DPA10301-DPB10202, DPA10301-DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301- DPB14001, DPA10301-DPB16501, DPA10401-DPB10201, DPA10401-DPB10202, DQA10102-DQB10501, DQA10102-DQB10503, DQA10102-DQB10604, DQA10102- DQB10609, DQA10103-DQB10501, and DQA10103-DQB10609. [1840] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA G118D protein mutation comprises SEQ ID NO: 1015, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0901, DRB1_1001, DPA10301-DPB10101, DPA10401- - 361 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPB10101, DPA10401-DPB11401, DQA10102-DQB10501, DQA10102-DQB10503, DQA10102-DQB10601, DQA10102-DQB10609, DQA10102-DQB10611, DQA10103- DQB10501, DQA10103-DQB10601, DQA10103-DQB10609, DQA10201-DQB10301, DQA10201-DQB10302, DQA10201-DQB10303, DQA10301-DQB10301, DQA10302- DQB10301, DQA10303-DQB10301, DQA10401-DQB10301, DQA10401-DQB10319, DQA10501-DQB10203, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503- DQB10301, DQA10505-DQB10301, DQA10505-DQB10302, DQA10505-DQB10309, DQA10505-DQB10319, DQA10506-DQB10303, DQA10508-DQB10301, DQA10509- DQB10301, and DQA10601-DQB10301. [1841] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 1016, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1304, DRB1_1406, DRB1_1602, and DQA10102-DQB10501. [1842] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 1017, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1304, DRB1_1406, DRB1_1602, and DQA10102-DQB10501. [1843] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 1018, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1304, DRB1_1406, DRB1_1602, and DQA10102-DQB10501. [1844] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 1019, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 362 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1304, DRB1_1406, DRB1_1602, and DQA10102-DQB10501. [1845] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 1020, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0404, DRB1_0410, DRB1_1001, DRB1_1304, and DRB1_1406. [1846] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 1021, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1406, and DQA10102-DQB10501. [1847] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 1022, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0102, DRB1_0404, DRB1_0410, DRB1_1406, and DQA10102-DQB10501. [1848] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 1023, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1406, and DQA10102-DQB10501. [1849] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 1024, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1406, and DQA10102-DQB10501. - 363 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1850] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA H1047L protein mutation comprises SEQ ID NO: 1025, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101. [1851] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 1026, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103- DPB10501, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103-DPB11801, DPA10103-DPB11901, DPA10103-DPB13101, DPA10103-DPB13401, DPA10103- DPB14001, DPA10103-DPB14101, DPA10103-DPB14801, DPA10103-DPB15001, DPA10103-DPB15901, DPA10104-DPB10101, DPA10104-DPB11501, DPA10105- DPB10101, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106-DPB10101, DPA10201-DPB10101, DPA10201-DPB110601, DPA10201-DPB11501, DPA10201- DPB11601, DPA10201-DPB11801, DPA10201-DPB11901, DPA10201-DPB13401, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202- DPB10401, DPA10202-DPB10402, DPA10202-DPB10501, DPA10202-DPB10901, DPA10202-DPB110001, DPA10202-DPB110501, DPA10202-DPB110601, DPA10202- DPB11101, DPA10202-DPB11301, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202-DPB13101, DPA10202-DPB13801, DPA10202-DPB15501, DPA10202- DPB16501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10401, DPA10301-DPB10402, DPA10301-DPB110501, DPA10301- DPB110601, DPA10301-DPB11101, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301- DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10402, DPA10401- - 364 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPB10501, DPA10401-DPB110501, DPA10401-DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, and DPA10401-DPB14901. [1852] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 1027, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1101, DRB1_1114, DRB1_1302, DRB1_1303, DRB1_1305, DRB1_1312, DRB1_1402, DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10401, DPA10103-DPB10402, DPA10103-DPB10501, DPA10103- DPB110501, DPA10103-DPB112601, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103-DPB11801, DPA10103-DPB11901, DPA10103-DPB12301, DPA10103- DPB13101, DPA10103-DPB13401, DPA10103-DPB13901, DPA10103-DPB14001, DPA10103-DPB14101, DPA10103-DPB14801, DPA10103-DPB14901, DPA10103- DPB15001, DPA10103-DPB15101, DPA10103-DPB15901, DPA10103-DPB18001, DPA10104-DPB10101, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105- DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106-DPB10101, DPA10201-DPB10101, DPA10201-DPB10201, DPA10201-DPB10202, DPA10201- DPB10401, DPA10201-DPB110601, DPA10201-DPB11501, DPA10201-DPB11601, DPA10201-DPB11801, DPA10201-DPB11901, DPA10201-DPB13401, DPA10202- DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202-DPB10401, DPA10202-DPB10402, DPA10202-DPB10501, DPA10202-DPB10901, DPA10202- DPB110001, DPA10202-DPB110501, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202- DPB13101, DPA10202-DPB13801, DPA10202-DPB15501, DPA10202-DPB16501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301- DPB10401, DPA10301-DPB10402, DPA10301-DPB110501, DPA10301-DPB110601, DPA10301-DPB11101, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301- DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301-DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401- DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, DPA10401-DPB11301, DPA10401- DPB113301, DPA10401-DPB11401, DPA10401-DPB14901, and DQA10102-DQB10501. - 365 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1853] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 1028, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10401, DPA10103-DPB10501, DPA10103-DPB112601, DPA10103- DPB11501, DPA10103-DPB11601, DPA10103-DPB11801, DPA10103-DPB11901, DPA10103-DPB12301, DPA10103-DPB13101, DPA10103-DPB13401, DPA10103- DPB13901, DPA10103-DPB14001, DPA10103-DPB14101, DPA10103-DPB14801, DPA10103-DPB15001, DPA10103-DPB15901, DPA10104-DPB10101, DPA10104- DPB11501, DPA10105-DPB10101, DPA10105-DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106-DPB10101, DPA10201-DPB10101, DPA10201- DPB110601, DPA10201-DPB11501, DPA10201-DPB11601, DPA10201-DPB11801, DPA10201-DPB11901, DPA10201-DPB13401, DPA10202-DPB10101, DPA10202- DPB10201, DPA10202-DPB10202, DPA10202-DPB10401, DPA10202-DPB10501, DPA10202-DPB110001, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202- DPB11801, DPA10202-DPB11901, DPA10202-DPB13101, DPA10202-DPB13801, DPA10202-DPB15501, DPA10202-DPB16501, DPA10301-DPB10101, DPA10301- DPB10401, DPA10301-DPB10402, DPA10301-DPB110501, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301- DPB14901, DPA10301-DPB15501, DPA10301-DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401- DPB10202, DPA10401-DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, and DPA10401-DPB14901. [1854] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 1029, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0806, - 366 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1101, DRB1_1102, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103- DPB10401, DPA10103-DPB10402, DPA10103-DPB10501, DPA10103-DPB110501, DPA10103-DPB112601, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103- DPB11801, DPA10103-DPB11901, DPA10103-DPB12301, DPA10103-DPB13101, DPA10103-DPB13401, DPA10103-DPB13901, DPA10103-DPB14001, DPA10103- DPB14101, DPA10103-DPB14801, DPA10103-DPB14901, DPA10103-DPB15001, DPA10103-DPB15101, DPA10103-DPB15901, DPA10103-DPB18001, DPA10104- DPB10101, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105-DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106-DPB10101, DPA10201- DPB10101, DPA10201-DPB10201, DPA10201-DPB10202, DPA10201-DPB10401, DPA10201-DPB110601, DPA10201-DPB11501, DPA10201-DPB11601, DPA10201- DPB11801, DPA10201-DPB11901, DPA10201-DPB13401, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202-DPB10401, DPA10202- DPB10402, DPA10202-DPB10501, DPA10202-DPB10901, DPA10202-DPB110001, DPA10202-DPB110501, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202- DPB11301, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202-DPB13101, DPA10202-DPB13801, DPA10202-DPB15501, DPA10202-DPB16501, DPA10301- DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10401, DPA10301-DPB10402, DPA10301-DPB110501, DPA10301-DPB110601, DPA10301- DPB11101, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301- DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10402, DPA10401- DPB10501, DPA10401-DPB110501, DPA10401-DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, DPA10401-DPB14901, and DQA10102-DQB10501. [1855] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 1030, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0405, DRB1_0408, DRB1_0701, DRB1_0802, DRB1_0809, DRB1_0813, - 367 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DRB1_0901, DRB1_1001, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10201-DPB110601, DPA10201-DPB11901, DPA10202-DPB10101, DPA10202- DPB10201, DPA10202-DPB10401, DPA10202-DPB10501, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202- DPB13101, DPA10202-DPB13801, DPA10202-DPB15501, DPA10202-DPB16501, DPA10301-DPB15501, DQA10102-DQB10501, DQA10102-DQB10503, DQA10103- DQB10501, and DQA10103-DQB10609. [1856] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 1031, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0404, DRB1_0801, DRB1_0803, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1404, DRB1_1406, and DRB1_1454. [1857] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 1032, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DPA10103- DPB11501, DPA10103-DPB11801, DPA10103-DPB13401, DPA10103-DPB14001, DPA10104-DPB11501, DPA10105-DPB11801, DPA10201-DPB11501, DPA10201- DPB13401, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202-DPB10501, DPA10202-DPB110601, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202- DPB13101, DPA10202-DPB13801, DPA10202-DPB16501, DPA10301-DPB14001, DPA10401-DPB10201, and DPA10401-DPB10202. [1858] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 1033, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 368 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DQA10102-DQB10601, DQA10102-DQB10602, DQA10103-DQB10601, DQA10103- DQB10602, and DQA10103-DQB10609. [1859] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 1034, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0701, DRB1_0901, and DRB1_1001. [1860] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA N345K protein mutation comprises SEQ ID NO: 1035, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0301. [1861] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 1036, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10202, DPA10103-DPB11601, DPA10202-DPB110601, DPA10202- DPB11901, DPA10301-DPB110601, and DPA10401-DPB10202. [1862] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 1037, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10202, DPA10103-DPB11601, DPA10202-DPB110601, DPA10202- DPB11901, DPA10301-DPB110601, and DPA10401-DPB10202. [1863] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 1038, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10202, DPA10103-DPB11601, DPA10202-DPB110601, DPA10202- DPB11901, DPA10301-DPB110601, and DPA10401-DPB10202. - 369 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1864] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 1039, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10202, DPA10103-DPB11601, DPA10202-DPB110601, DPA10202- DPB11901, DPA10301-DPB110601, and DPA10401-DPB10202. [1865] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 1040, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10202-DPB110601, DPA10202-DPB11901, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB110601, DPA10401-DPB10201, and DPA10401-DPB10202. [1866] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 1041, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10202-DPB110601, DPA10202-DPB11901, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB110601, DPA10401-DPB10201, and DPA10401-DPB10202. [1867] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 1042, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10202, DPA10103-DPB11601, and DPA10301-DPB110601. [1868] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 1043, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10202, DPA10103-DPB11601, and DPA10301-DPB110601. [1869] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 1044, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 370 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10202, DPA10103-DPB11601, and DPA10301-DPB110601. [1870] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546K protein mutation comprises SEQ ID NO: 1045, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10202, DPA10103-DPB11601, and DPA10301-DPB110601. [1871] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 1046, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11601, DPA10103-DPB11901, DPA10201-DPB110601, DPA10201- DPB11901, and DPA10301-DPB110601. [1872] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 1047, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11601, DPA10103-DPB11901, DPA10201-DPB110601, DPA10201- DPB11901, and DPA10301-DPB110601. [1873] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 1048, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11601, DPA10103-DPB11901, DPA10201-DPB110601, DPA10201- DPB11901, and DPA10301-DPB110601. [1874] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 1049, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10202, DPA10103-DPB11601, DPA10103-DPB11901, DPA10202- DPB110601, DPA10202-DPB11901, DPA10301-DPB110601, and DPA10401-DPB10202. - 371 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1875] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 1050, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10202, DPA10103-DPB11601, DPA10103-DPB11901, DPA10202- DPB110601, DPA10202-DPB11901, DPA10301-DPB110601, and DPA10401-DPB10202. [1876] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 1051, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10202, DPA10103-DPB11601, DPA10103-DPB11901, DPA10202- DPB110601, DPA10202-DPB11901, DPA10301-DPB110601, and DPA10401-DPB10202. [1877] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 1052, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB110601, DPA10301- DPB11801, and DPA10301-DPB14001. [1878] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 1053, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB110601, and DPA10301- DPB14001. [1879] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 1054, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB110601, DPA10301- DPB11801, and DPA10301-DPB14001. - 372 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1880] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA Q546R protein mutation comprises SEQ ID NO: 1055, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB110601, DPA10301- DPB11801, and DPA10301-DPB14001. [1881] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 1056, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0405, DRB1_1501, DRB1_1503, DRB1_1602, DQA10102-DQB10501, and DQA10103-DQB10501. [1882] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 1057, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0405 and DRB1_1602. [1883] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 1058, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001 and DQA10102-DQB10501. [1884] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 1059, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1114 and DRB1_1302. [1885] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 1060, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 373 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DRB1_0404, DRB1_0405, DRB1_0410, DRB1_0806, DRB1_1502, and DQA10102- DQB10501. [1886] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 1061, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1103, DRB1_1304, DRB1_1501, DRB1_1502, DRB1_1503, DQA10102-DQB10501, DQA10102-DQB10503, and DQA10103-DQB10501. [1887] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 1062, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1103, DRB1_1104, DRB1_1304, DRB1_1501, DRB1_1503, DQA10102-DQB10501, and DQA10103-DQB10501. [1888] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 1063, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0806, DRB1_1103, DRB1_1104, and DRB1_1304. [1889] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 1064, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0806, DRB1_1103, DRB1_1104, DRB1_1304, DRB1_1501, and DRB1_1503. [1890] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a PIK3CA R108H protein mutation comprises SEQ ID NO: 1065, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501, DQA10102-DQB10503, and DQA10103-DQB10501. [1891] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 1066, wherein a peptide with this - 374 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1101, DRB1_1104, and DRB1_1305. [1892] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 1067, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804 and DRB1_0806. [1893] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 1068, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804 and DRB1_0806. [1894] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 1069, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501 and DPA10104-DPB11501. [1895] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 1070, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1101, DRB1_1104, and DRB1_1305. [1896] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 1071, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1305, and DRB1_1406. [1897] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 1072, wherein a peptide with this - 375 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1305, and DRB1_1406. [1898] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 1073, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1305, and DRB1_1406. [1899] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 1074, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804, DRB1_1101, DRB1_1103, DRB1_1104, DRB1_1305, and DRB1_1406. [1900] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176F protein mutation comprises SEQ ID NO: 1075, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0806, DRB1_1102, DRB1_1301, and DRB1_1304. [1901] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 1076, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1101, DRB1_1104, and DRB1_1305. [1902] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 1077, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1101, DRB1_1104, and DRB1_1305. - 376 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1903] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 1078, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1101, DRB1_1104, and DRB1_1305. [1904] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 1079, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, and DRB1_1406. [1905] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 1080, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, and DRB1_1406. [1906] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 1081, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, and DRB1_1406. [1907] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 1082, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804, DRB1_1101, DRB1_1103, DRB1_1104, and DRB1_1305. [1908] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 1083, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 377 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804, DRB1_1101, DRB1_1103, DRB1_1104, and DRB1_1305. [1909] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 1084, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0806. [1910] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C176Y protein mutation comprises SEQ ID NO: 1085, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501 and DPA10104-DPB11501. [1911] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 1086, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10201, and DPA10301- DPB10202. [1912] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 1087, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_1001, DRB1_1501, DRB1_1602, and DQA10103-DQB10501. [1913] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 1088, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_1001, DRB1_1501, DRB1_1602, and DQA10103-DQB10501. - 378 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1914] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 1089, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1301, and DRB1_1304. [1915] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 1090, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1114, DRB1_1302, DRB1_1402, DRB1_1601, DRB1_1602, DQA10103-DQB10609, and DQA10505-DQB10402. [1916] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 1091, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0405, DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1114, DRB1_1302, DRB1_1402, DRB1_1601, DRB1_1602, DQA10103- DQB10609, and DQA10505-DQB10402. [1917] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 1092, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1114, DRB1_1302, DRB1_1402, DRB1_1601, DRB1_1602, DQA10103-DQB10609, and DQA10505-DQB10402. [1918] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 1093, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, - 379 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1402, DRB1_1601, DRB1_1602, DQA10103- DQB10609, and DQA10505-DQB10402. [1919] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 1094, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10201-DQB10301, DQA10501-DQB10301, DQA10501-DQB10319, DQA10503- DQB10301, DQA10505-DQB10301, DQA10505-DQB10309, DQA10505-DQB10319, DQA10508-DQB10301, and DQA10509-DQB10301. [1920] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C238Y protein mutation comprises SEQ ID NO: 1095, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1101 and DRB1_1305. [1921] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 1096, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, and DRB1_1301. [1922] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 1097, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, and DRB1_1301. [1923] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 1098, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10103-DQB10601. [1924] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 1099, wherein a peptide with this - 380 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10101, DPA10103-DPB10601, DPA10103-DPB11101, DPA10103- DPB11601, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103-DPB13101, DPA10103-DPB15001, DPA10104-DPB10101, DPA10105-DPB10101, DPA10105- DPB15001, DPA10301-DPB10101, DPA10301-DPB10301, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401- DPB113301, and DPA10401-DPB11401. [1925] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 1100, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10101, DPA10103-DPB10301, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103-DPB13101, DPA10103- DPB15001, DPA10104-DPB10101, DPA10104-DPB10301, DPA10105-DPB10101, DPA10105-DPB10301, DPA10105-DPB15001, DPA10301-DPB10101, DPA10301- DPB10301, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. [1926] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 1101, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10101, DPA10103-DPB10301, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103-DPB13101, DPA10103- DPB15001, DPA10104-DPB10101, DPA10104-DPB10301, DPA10105-DPB10101, DPA10105-DPB10301, DPA10105-DPB15001, DPA10301-DPB10101, DPA10301- DPB10301, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. [1927] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 1102, wherein a peptide with this - 381 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10101, DPA10103-DPB10301, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103-DPB13101, DPA10103- DPB15001, DPA10104-DPB10101, DPA10104-DPB10301, DPA10105-DPB10101, DPA10105-DPB10301, DPA10105-DPB15001, DPA10301-DPB10101, DPA10301- DPB10301, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. [1928] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 1103, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10101, DPA10103-DPB10301, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103-DPB13101, DPA10103- DPB15001, DPA10104-DPB10101, DPA10104-DPB10301, DPA10105-DPB10101, DPA10105-DPB10301, DPA10105-DPB15001, DPA10301-DPB10101, DPA10301- DPB10301, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. [1929] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 1104, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10101, DPA10103-DPB10301, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103-DPB13101, DPA10103- DPB15001, DPA10104-DPB10101, DPA10104-DPB10301, DPA10105-DPB10101, DPA10105-DPB10301, DPA10105-DPB15001, DPA10301-DPB10101, DPA10301- DPB10301, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. - 382 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1930] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 C275Y protein mutation comprises SEQ ID NO: 1105, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001 and DQA10103-DQB10501. [1931] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 1106, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, and DRB1_1406. [1932] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 1107, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, and DRB1_1406. [1933] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 1108, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001. [1934] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 1109, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, and DRB1_1304. [1935] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 1110, wherein a peptide with this - 383 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0804, DRB1_0806, DRB1_1102, DRB1_1103, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, and DRB1_1406. [1936] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 1111, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, and DRB1_1406. [1937] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 1112, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, and DRB1_1406. [1938] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 1113, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, and DRB1_1406. [1939] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 1114, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, and DRB1_1406. - 384 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1940] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245S protein mutation comprises SEQ ID NO: 1115, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101. [1941] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 1116, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601 and DQA10103-DQB10601. [1942] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 1117, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601 and DQA10103-DQB10601. [1943] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 1118, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, and DRB1_1406. [1944] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 1119, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0801, DRB1_0806, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, and DRB1_1406. [1945] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 1120, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 385 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0801, DRB1_0804, DRB1_1001, DRB1_1101, DRB1_1305, and DRB1_1406. [1946] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 1121, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_1101, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1404, DRB1_1405, DRB1_1406, and DRB1_1454. [1947] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 1122, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1405, DRB1_1406, and DRB1_1454. [1948] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 1123, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1405, and DRB1_1406. [1949] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 1124, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1114, DRB1_1302, and DRB1_1501. [1950] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 G245V protein mutation comprises SEQ ID NO: 1125, wherein a peptide with this - 386 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1404, DRB1_1406, DRB1_1454, and DRB1_1501. [1951] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 1126, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1103, DRB1_1104, and DRB1_1406. [1952] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 1127, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, and DRB1_1406. [1953] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 1128, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, and DRB1_1406. [1954] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 1129, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1301, DRB1_1304, and DRB1_1406. [1955] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 1130, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, and DRB1_1406. - 387 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1956] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 1131, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, and DRB1_1406. [1957] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 1132, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, and DRB1_1406. [1958] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 1133, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, and DRB1_1406. [1959] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 1134, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, and DRB1_1406. [1960] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H179Y protein mutation comprises SEQ ID NO: 1135, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, and DRB1_1406. [1961] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 1136, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_1101, and DRB1_1305. - 388 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1962] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 1137, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_1101, DRB1_1104, and DRB1_1305. [1963] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 1138, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001, DPA10103-DPB10101, DPA10103-DPB15001, DPA10104-DPB10101, DPA10105-DPB10101, DPA10105-DPB15001, DPA10301-DPB10101, DPA10301- DPB110601, DPA10301-DPB16501, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11401, DQA10102-DQB10501, DQA10103- DQB10501, and DQA10103-DQB10609. [1964] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 1139, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001, DPA10103-DPB10101, DPA10103-DPB15001, DPA10104-DPB10101, DPA10105-DPB10101, DPA10105-DPB15001, DPA10301-DPB10101, DPA10301- DPB110601, DPA10301-DPB16501, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11401, DQA10102-DQB10501, DQA10103- DQB10501, and DQA10103-DQB10609. [1965] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 1140, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001, DPA10103-DPB10101, DPA10103-DPB15001, DPA10104-DPB10101, DPA10105-DPB10101, DPA10105-DPB15001, DPA10301-DPB10101, DPA10301- DPB110601, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11401, DQA10102-DQB10501, DQA10103-DQB10501, and DQA10103-DQB10609. - 389 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1966] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 1141, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001, DPA10103-DPB10101, DPA10103-DPB15001, DPA10104-DPB10101, DPA10105-DPB10101, DPA10105-DPB15001, DPA10301-DPB10101, DPA10301- DPB110601, DPA10301-DPB16501, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11401, DQA10102-DQB10501, DQA10103- DQB10501, and DQA10103-DQB10609. [1967] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 1142, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10501, DPA10103-DPB13101, DPA10103-DPB15001, DPA10105- DPB15001, DPA10401-DPB10301, DPA10401-DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, and DQA10103-DQB10609. [1968] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 1143, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10501, DPA10103-DPB15001, DPA10105-DPB15001, DPA10401- DPB10301, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401-DPB11401. [1969] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 1144, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0806 and DRB1_1104. [1970] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 H193R protein mutation comprises SEQ ID NO: 1145, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1104. - 390 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1971] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 1146, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1406, DPA10202-DPB10101, DPA10301-DPB11801, and DPA10301- DPB14001. [1972] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 1147, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10202-DPB10101, DPA10301-DPB11801, and DPA10301-DPB14001. [1973] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 1148, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0301, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, and DRB1_1406. [1974] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 1149, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0301, DRB1_1114, DRB1_1302, and DRB1_1406. [1975] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 1150, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, and DRB1_1406. [1976] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 1151, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 391 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0301, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, and DRB1_1406. [1977] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 1152, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0301, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1304, and DRB1_1406. [1978] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 1153, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_1104, and DRB1_1501. [1979] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 1154, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_1102, DRB1_1104, DRB1_1301, DRB1_1406, and DRB1_1501. [1980] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 I195T protein mutation comprises SEQ ID NO: 1155, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_1102, DRB1_1104, DRB1_1301, DRB1_1406, and DRB1_1501. [1981] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 1156, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10301-DPB10401, DPA10301-DPB12301, and DPA10301-DPB13901. - 392 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1982] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 1157, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001, DQA10102-DQB10501, DQA10102-DQB10503, DQA10103-DQB10501, and DQA10103-DQB10609. [1983] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 1158, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DQA10102-DQB10501, DQA10102-DQB10503, DQA10103- DQB10501, and DQA10103-DQB10609. [1984] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 1159, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501 and DPA10104-DPB11501. [1985] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 1160, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0701, DRB1_1001, DPA10103-DPB10101, DPA10104-DPB10101, DPA10105-DPB10101, DPA10202-DPB10101, DPA10301-DPB10101, DPA10301- DPB11801, DPA10301-DPB14001, DPA10401-DPB10101, and DPA10401-DPB10201. [1986] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 1161, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0405, DRB1_0701, DRB1_0901, DRB1_1001, DPA10103-DPB10101, DPA10104-DPB10101, DPA10105-DPB10101, DPA10202-DPB10101, DPA10301- DPB10101, DPA10301-DPB11801, DPA10301-DPB14001, DPA10401-DPB10101, DPA10401-DPB10201, and DQA10102-DQB10501. - 393 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [1987] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 1162, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0405, DRB1_0701, DRB1_0901, DRB1_1001, DPA10103-DPB10101, DPA10104-DPB10101, DPA10105-DPB10101, DPA10202-DPB10101, DPA10301- DPB11801, and DPA10401-DPB10101. [1988] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 1163, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0405, DRB1_1001, DPA10103-DPB10101, DPA10104-DPB10101, DPA10105-DPB10101, DPA10202-DPB10101, DPA10301-DPB10101, DPA10301- DPB11801, DPA10301-DPB14001, DPA10401-DPB10101, and DPA10401-DPB10201. [1989] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 1164, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0405, DRB1_0701, DRB1_0901, DRB1_1001, DPA10103-DPB10101, DPA10104-DPB10101, DPA10105-DPB10101, DPA10202-DPB10101, DPA10301- DPB10101, DPA10301-DPB11801, DPA10301-DPB14001, DPA10401-DPB10101, DPA10401-DPB10201, and DQA10102-DQB10501. [1990] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132E protein mutation comprises SEQ ID NO: 1165, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0701, DRB1_0901, DRB1_1001, DPA10103-DPB10101, DPA10104- DPB10101, DPA10105-DPB10101, DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB11801, DPA10301-DPB14001, DPA10401-DPB10101, DPA10401- DPB10201, and DQA10102-DQB10501. [1991] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 1166, wherein a peptide with this - 394 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0405, DRB1_0701, DRB1_0901, and DRB1_1602. [1992] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 1167, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0405, DRB1_0701, DRB1_0901, and DRB1_1602. [1993] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 1168, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0405. [1994] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 1169, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0404, DRB1_0408, DRB1_0410, DRB1_1001, DPA10202-DPB10101, DPA10301-DPB11801, DQA10102-DQB10501, DQA10102- DQB10503, DQA10103-DQB10501, and DQA10103-DQB10609. [1995] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 1170, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DPA10103-DPB11501, DPA10104-DPB11501, DPA10202- DPB10101, DPA10301-DPB10101, DPA10301-DPB10402, DPA10301-DPB110501, DPA10301-DPB11801, DPA10301-DPB14901, DPA10301-DPB16501, DPA10301- DPB18001, DQA10102-DQB10501, and DQA10103-DQB10501. [1996] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 1171, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 395 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_1001, DPA10103-DPB11501, DPA10104-DPB11501, DPA10202- DPB10101, DPA10301-DPB10101, DPA10301-DPB10402, DPA10301-DPB110501, DPA10301-DPB11801, DPA10301-DPB14901, DPA10301-DPB16501, DPA10301- DPB18001, DQA10102-DQB10501, and DQA10103-DQB10501. [1997] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 1172, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1114, DRB1_1302, DRB1_1304, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10401, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301- DPB13901, DPA10301-DPB14001, DQA10102-DQB10501, DQA10102-DQB10503, and DQA10103-DQB10501. [1998] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 1173, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1114, DRB1_1302, DRB1_1304, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10401, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301- DPB13901, DPA10301-DPB14001, DQA10102-DQB10501, DQA10102-DQB10503, and DQA10103-DQB10501. [1999] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 1174, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0410, DRB1_1001, DRB1_1114, DRB1_1302, DRB1_1304, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB11801, DPA10301- DPB14001, DQA10102-DQB10501, and DQA10103-DQB10501. [2000] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 K132N protein mutation comprises SEQ ID NO: 1175, wherein a peptide with this - 396 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1114, DRB1_1302, DRB1_1304, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10401, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301- DPB13901, DPA10301-DPB14001, DQA10102-DQB10501, DQA10102-DQB10503, and DQA10103-DQB10501. [2001] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 1176, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1104 and DRB1_1406. [2002] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 1177, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1104 and DRB1_1406. [2003] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 1178, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1104 and DRB1_1406. [2004] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 1179, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0401. [2005] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 1180, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 397 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0401. [2006] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 1181, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0401. [2007] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 1182, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0301. [2008] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 1183, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0301. [2009] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 1184, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0301. [2010] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 P151S protein mutation comprises SEQ ID NO: 1185, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0301. [2011] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 1186, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 398 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DRB1_0101, DRB1_0103, DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1114, DRB1_1201, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, DRB1_1402, DRB1_1403, DRB1_1407, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103- DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10401, DPA10103-DPB112601, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103- DPB11801, DPA10103-DPB11901, DPA10103-DPB12301, DPA10103-DPB13101, DPA10103-DPB13401, DPA10103-DPB13901, DPA10103-DPB14001, DPA10103- DPB14101, DPA10103-DPB14801, DPA10103-DPB15001, DPA10103-DPB15501, DPA10103-DPB15901, DPA10104-DPB10101, DPA10104-DPB11501, DPA10105- DPB10101, DPA10105-DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106-DPB10101, DPA10201-DPB10101, DPA10201-DPB10202, DPA10201- DPB110601, DPA10201-DPB11501, DPA10201-DPB11901, DPA10201-DPB13401, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202- DPB10401, DPA10202-DPB10501, DPA10202-DPB10901, DPA10202-DPB110001, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202- DPB11401, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202-DPB12901, DPA10202-DPB13101, DPA10202-DPB13801, DPA10202-DPB15501, DPA10202- DPB16501, DPA10202-DPB18501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10401, DPA10301-DPB10402, DPA10301- DPB10901, DPA10301-DPB110501, DPA10301-DPB110601, DPA10301-DPB11101, DPA10301-DPB11301, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301- DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301-DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401- DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10301, DPA10401-DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, DPA10401- DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, DPA10401-DPB14901, DQA10501-DQB10501, and DQA10505-DQB10501. [2012] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 1187, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0103, DRB1_0401, DRB1_0408, DRB1_0701, - 399 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1201, DRB1_1202, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103- DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10401, DPA10103-DPB112601, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103- DPB11801, DPA10103-DPB11901, DPA10103-DPB12301, DPA10103-DPB13101, DPA10103-DPB13401, DPA10103-DPB13901, DPA10103-DPB14001, DPA10103- DPB14101, DPA10103-DPB14801, DPA10103-DPB15001, DPA10103-DPB15501, DPA10103-DPB15901, DPA10104-DPB10101, DPA10104-DPB11501, DPA10105- DPB10101, DPA10105-DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106-DPB10101, DPA10201-DPB10101, DPA10201-DPB10202, DPA10201- DPB110601, DPA10201-DPB11501, DPA10201-DPB11901, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202-DPB10401, DPA10202- DPB10501, DPA10202-DPB10901, DPA10202-DPB110001, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202-DPB11401, DPA10202- DPB11801, DPA10202-DPB11901, DPA10202-DPB12901, DPA10202-DPB13101, DPA10202-DPB13801, DPA10202-DPB15501, DPA10202-DPB16501, DPA10202- DPB18501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10401, DPA10301-DPB10402, DPA10301-DPB10901, DPA10301- DPB110501, DPA10301-DPB110601, DPA10301-DPB11101, DPA10301-DPB11301, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301- DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301-DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401-DPB10101, DPA10401- DPB10201, DPA10401-DPB10202, DPA10401-DPB10301, DPA10401-DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, DPA10401-DPB11301, DPA10401- DPB113301, DPA10401-DPB11401, DPA10401-DPB14901, DQA10501-DQB10501, DQA10505-DQB10402, and DQA10505-DQB10501. [2013] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 1188, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 400 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DRB1_0101, DRB1_0102, DRB1_0103, DRB1_0401, DRB1_0408, DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1201, DRB1_1202, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10401, DPA10103- DPB112601, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103-DPB11801, DPA10103-DPB11901, DPA10103-DPB12301, DPA10103-DPB13101, DPA10103- DPB13401, DPA10103-DPB13901, DPA10103-DPB14001, DPA10103-DPB14101, DPA10103-DPB14801, DPA10103-DPB15001, DPA10103-DPB15501, DPA10103- DPB15901, DPA10104-DPB10101, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105-DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106- DPB10101, DPA10201-DPB10101, DPA10201-DPB10202, DPA10201-DPB110601, DPA10201-DPB11501, DPA10201-DPB11901, DPA10201-DPB13401, DPA10202- DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202-DPB10401, DPA10202-DPB10501, DPA10202-DPB10901, DPA10202-DPB110001, DPA10202- DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202-DPB11401, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202-DPB12901, DPA10202- DPB13101, DPA10202-DPB13801, DPA10202-DPB15501, DPA10202-DPB16501, DPA10202-DPB18501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB10401, DPA10301-DPB10402, DPA10301-DPB10901, DPA10301-DPB110501, DPA10301-DPB110601, DPA10301-DPB11101, DPA10301- DPB11301, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301- DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10301, DPA10401- DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, DPA10401-DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, DPA10401-DPB14901, DQA10501- DQB10501, DQA10505-DQB10402, and DQA10505-DQB10501. [2014] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 1189, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 401 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0103, DRB1_0401, DRB1_0408, DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1201, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10401, DPA10103- DPB112601, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103-DPB11901, DPA10103-DPB12301, DPA10103-DPB13101, DPA10103-DPB13401, DPA10103- DPB13901, DPA10103-DPB14801, DPA10103-DPB15001, DPA10103-DPB15501, DPA10103-DPB15901, DPA10104-DPB10101, DPA10104-DPB11501, DPA10105- DPB10101, DPA10105-DPB10401, DPA10105-DPB15001, DPA10201-DPB11501, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202- DPB10401, DPA10202-DPB10901, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202-DPB11401, DPA10202-DPB11901, DPA10202- DPB12901, DPA10202-DPB13101, DPA10202-DPB15501, DPA10202-DPB16501, DPA10202-DPB18501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB10401, DPA10301-DPB10402, DPA10301-DPB10901, DPA10301-DPB110501, DPA10301-DPB110601, DPA10301-DPB11101, DPA10301- DPB11301, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301- DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10301, DPA10401- DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, DPA10401-DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, DPA10401-DPB14901, DQA10102- DQB10601, DQA10103-DQB10601, DQA10501-DQB10501, DQA10505-DQB10402, and DQA10505-DQB10501. [2015] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 1190, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0701, DRB1_0801, DRB1_0802, DRB1_0803, - 402 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103-DPB10401, DPA10103-DPB112601, DPA10103- DPB11501, DPA10103-DPB11601, DPA10103-DPB11801, DPA10103-DPB11901, DPA10103-DPB12301, DPA10103-DPB13101, DPA10103-DPB13401, DPA10103- DPB13901, DPA10103-DPB14001, DPA10103-DPB14101, DPA10103-DPB14801, DPA10103-DPB15001, DPA10103-DPB15501, DPA10103-DPB15901, DPA10104- DPB10101, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105-DPB10401, DPA10105-DPB11801, DPA10105-DPB15001, DPA10106-DPB10101, DPA10201- DPB10101, DPA10201-DPB10202, DPA10201-DPB110601, DPA10201-DPB11501, DPA10201-DPB11901, DPA10201-DPB13401, DPA10202-DPB10101, DPA10202- DPB10201, DPA10202-DPB10202, DPA10202-DPB10401, DPA10202-DPB10501, DPA10202-DPB10901, DPA10202-DPB110001, DPA10202-DPB110601, DPA10202- DPB11101, DPA10202-DPB11301, DPA10202-DPB11401, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202-DPB12901, DPA10202-DPB13101, DPA10202- DPB13801, DPA10202-DPB15501, DPA10202-DPB16501, DPA10202-DPB18501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301- DPB10401, DPA10301-DPB10402, DPA10301-DPB10901, DPA10301-DPB110501, DPA10301-DPB110601, DPA10301-DPB11101, DPA10301-DPB11301, DPA10301- DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301-DPB15501, DPA10301-DPB16501, DPA10301- DPB17501, DPA10301-DPB18001, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401-DPB10301, DPA10401-DPB10402, DPA10401- DPB10501, DPA10401-DPB110501, DPA10401-DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, and DPA10401-DPB14901. [2016] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 1191, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0701, DRB1_0801, DRB1_0803, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, - 403 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1404, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB10101, DPA10103-DPB10201, DPA10103-DPB10202, DPA10103- DPB10401, DPA10103-DPB112601, DPA10103-DPB11501, DPA10103-DPB11601, DPA10103-DPB11801, DPA10103-DPB11901, DPA10103-DPB12301, DPA10103- DPB13101, DPA10103-DPB13401, DPA10103-DPB13901, DPA10103-DPB14001, DPA10103-DPB14101, DPA10103-DPB14801, DPA10103-DPB15001, DPA10103- DPB15501, DPA10103-DPB15901, DPA10104-DPB10101, DPA10104-DPB11501, DPA10105-DPB10101, DPA10105-DPB10401, DPA10105-DPB11801, DPA10105- DPB15001, DPA10106-DPB10101, DPA10201-DPB10101, DPA10201-DPB10202, DPA10201-DPB110601, DPA10201-DPB11501, DPA10201-DPB11901, DPA10201- DPB13401, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202-DPB10401, DPA10202-DPB10501, DPA10202-DPB10901, DPA10202- DPB110001, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202-DPB11401, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202- DPB12901, DPA10202-DPB13101, DPA10202-DPB13801, DPA10202-DPB15501, DPA10202-DPB16501, DPA10202-DPB18501, DPA10301-DPB10101, DPA10301- DPB10201, DPA10301-DPB10202, DPA10301-DPB10401, DPA10301-DPB10402, DPA10301-DPB10901, DPA10301-DPB110501, DPA10301-DPB110601, DPA10301- DPB11101, DPA10301-DPB11301, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB14901, DPA10301- DPB15501, DPA10301-DPB16501, DPA10301-DPB17501, DPA10301-DPB18001, DPA10401-DPB10101, DPA10401-DPB10201, DPA10401-DPB10202, DPA10401- DPB10301, DPA10401-DPB10402, DPA10401-DPB10501, DPA10401-DPB110501, DPA10401-DPB11301, DPA10401-DPB113301, DPA10401-DPB11401, and DPA10401- DPB14901. [2017] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 1192, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0103, DRB1_0301, DRB1_0401, DRB1_0408, DRB1_0701, DRB1_0803, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1102, DRB1_1114, DRB1_1201, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1312, DRB1_1401, - 404 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1602, DPA10103-DPB10101, DPA10103-DPB11501, DPA10104-DPB10101, DPA10104-DPB11501, DPA10105-DPB10101, DPA10202- DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10401, DPA10301- DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB15501, DPA10301-DPB16501, DPA10401- DPB10101, DPA10401-DPB10201, and DPA10401-DPB10202. [2018] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 1193, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0301, DRB1_0401, DRB1_0408, DRB1_0813, DRB1_1001, DRB1_1102, DRB1_1114, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1402, DRB1_1403, DRB1_1406, DRB1_1501, DRB1_1502, and DRB1_1602. [2019] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 1194, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0103, DRB1_0401, DRB1_0408, DRB1_0701, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1201, DRB1_1202, DRB1_1301, DRB1_1302, DRB1_1304, DRB1_1305, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1407, DRB1_1454, DRB1_1501, DRB1_1502, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB10101, DPA10103-DPB11501, DPA10103-DPB13401, DPA10103-DPB15001, DPA10104-DPB10101, DPA10104- DPB11501, DPA10105-DPB10101, DPA10105-DPB15001, DPA10201-DPB11501, DPA10202-DPB10101, DPA10202-DPB10201, DPA10202-DPB10202, DPA10202- DPB10901, DPA10202-DPB110601, DPA10202-DPB11101, DPA10202-DPB11301, DPA10202-DPB11401, DPA10202-DPB11801, DPA10202-DPB11901, DPA10202- DPB15501, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301- - 405 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB15501, DPA10301-DPB16501, DPA10301-DPB17501, DPA10401-DPB10101, DPA10401- DPB10201, DPA10401-DPB10202, DPA10401-DPB10301, DPA10401-DPB11301, DPA10401-DPB113301, DQA10102-DQB10601, DQA10103-DQB10601, and DQA10505- DQB10402. [2020] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R213L protein mutation comprises SEQ ID NO: 1195, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0801, DRB1_0802, DRB1_0803, DRB1_0804, DRB1_0809, DRB1_0813, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1201, DRB1_1202, DRB1_1301, DRB1_1302, DRB1_1303, DRB1_1304, DRB1_1305, DRB1_1312, DRB1_1401, DRB1_1402, DRB1_1403, DRB1_1404, DRB1_1405, DRB1_1406, DRB1_1454, DRB1_1501, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10103-DPB13401, DPA10104-DPB11501, DPA10201-DPB11501, DPA10202- DPB10101, DPA10202-DPB11801, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB110601, DPA10301-DPB11801, and DPA10301-DPB14001. [2021] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 1196, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101 and DRB1_1001. [2022] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 1197, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301- DPB16501, and DPA10401-DPB10101. [2023] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 1198, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 406 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001. [2024] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 1199, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101 and DRB1_1001. [2025] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 1200, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1305, and DRB1_1406. [2026] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 1201, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1114, DRB1_1301, DRB1_1302, and DRB1_1304. [2027] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 1202, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1114 and DRB1_1302. [2028] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 1203, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0801, DRB1_0804, DRB1_0806, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, and DRB1_1406. - 407 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2029] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 1204, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1104, and DRB1_1301. [2030] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249M protein mutation comprises SEQ ID NO: 1205, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1103, DRB1_1301, and DRB1_1304. [2031] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 1206, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601. [2032] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 1207, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601. [2033] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 1208, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601. [2034] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 1209, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001. - 408 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2035] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 1210, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1001. [2036] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 1211, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DPA10103-DPB15001, DPA10105-DPB15001, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401- DPB11401. [2037] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 1212, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DPA10401-DPB10501, and DPA10401-DPB11401. [2038] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 1213, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DPA10401-DPB10301, and DPA10401-DPB11401. [2039] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 1214, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1301, DRB1_1304, and DRB1_1406. [2040] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R249S protein mutation comprises SEQ ID NO: 1215, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 409 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1301, and DRB1_1406. [2041] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 1216, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301- DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB16501, DPA10401- DPB10101, and DPA10401-DPB10201. [2042] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 1217, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301- DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB16501, DPA10401- DPB10101, and DPA10401-DPB10201. [2043] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 1218, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301- DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB16501, DPA10401- DPB10101, DPA10401-DPB10201, and DQA10102-DQB10501. [2044] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 1219, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301- DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, - 410 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB16501, DPA10401- DPB10101, and DPA10401-DPB10201. [2045] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 1220, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301- DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB16501, DPA10401- DPB10101, and DPA10401-DPB10201. [2046] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 1221, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301- DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB16501, DPA10401- DPB10101, and DPA10401-DPB10201. [2047] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 1222, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301- DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB16501, DPA10401- DPB10101, and DPA10401-DPB10201. [2048] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 1223, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10101, DPA10301- DPB10401, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB12301, - 411 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPA10301-DPB13901, DPA10301-DPB14001, DPA10301-DPB16501, DPA10401- DPB10101, and DQA10102-DQB10501. [2049] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 1224, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10101, DPA10103-DPB11501, DPA10104-DPB10101, DPA10104- DPB11501, DPA10105-DPB10101, and DPA10301-DPB15501. [2050] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 R273L protein mutation comprises SEQ ID NO: 1225, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101. [2051] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 1226, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0701, DRB1_0901, DRB1_1502, DRB1_1601, DRB1_1602, and DPA10301- DPB11801. [2052] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 1227, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0405, DRB1_0410, DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10202, and DPA10301-DPB14001. [2053] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 1228, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting - 412 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 of DRB1_0101, DRB1_0401, DRB1_0405, DRB1_0410, DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10104- DPB11501, DPA10301-DPB10201, DPA10301-DPB11801, DPA10401-DPB10201, and DPA10401-DPB10202. [2054] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 1229, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0405, DRB1_0410, DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10104- DPB11501, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB11801, DPA10301-DPB14001, DPA10401-DPB10201, and DPA10401-DPB10202. [2055] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 1230, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0405, DRB1_0410, DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB11801, DPA10301- DPB14001, DPA10401-DPB10201, and DPA10401-DPB10202. [2056] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 1231, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1102, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10104- DPB11501, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB11801, DPA10301-DPB14001, DPA10401-DPB10201, and DPA10401-DPB10202. - 413 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2057] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 1232, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0410, DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1503, DRB1_1601, DRB1_1602, and DPA10301-DPB11801. [2058] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 1233, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0410, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1503, DRB1_1601, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB11801, and DPA10301-DPB14001. [2059] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 1234, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0410, DRB1_1101, DRB1_1102, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1503, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB11801, and DPA10301-DPB14001. [2060] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S127Y protein mutation comprises SEQ ID NO: 1235, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0405, DRB1_0410, DRB1_0701, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1104, DRB1_1304, DRB1_1305, DRB1_1601, DRB1_1602, DPA10103-DPB11501, DPA10104-DPB11501, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB11801, and DPA10301-DPB14001. [2061] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 1236, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and - 414 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1601, and DRB1_1602. [2062] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 1237, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1601, and DRB1_1602. [2063] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 1238, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1601, DRB1_1602, and DQA10102-DQB10501. [2064] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 1239, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1601, DRB1_1602, DQA10102-DQB10501, and DQA10103-DQB10501. [2065] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 1240, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1601, DRB1_1602, DQA10102-DQB10501, and DQA10103-DQB10501. [2066] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 1241, wherein a peptide with this - 415 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1601, DRB1_1602, DQA10102-DQB10501, and DQA10103-DQB10501. [2067] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 1242, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1601, DRB1_1602, and DQA10102-DQB10501. [2068] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 1243, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1601, DRB1_1602, and DQA10102-DQB10501. [2069] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 1244, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_1001, DRB1_1601, DRB1_1602, DQA10102-DQB10501, and DQA10103-DQB10501. [2070] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 S241F protein mutation comprises SEQ ID NO: 1245, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10501. [2071] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 1246, wherein a peptide with this - 416 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10301, DPA10103-DPB10601, DPA10103-DPB112401, DPA10103- DPB113101, DPA10103-DPB11401, DPA10103-DPB11701, DPA10103-DPB12001, DPA10103-DPB12901, DPA10104-DPB10301, DPA10105-DPB10301, DPA10401- DPB10301, and DPA10401-DPB10501. [2072] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 1247, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10301, DPA10103-DPB10501, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB11901, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103- DPB15001, DPA10104-DPB10301, DPA10105-DPB10301, DPA10105-DPB15001, DPA10202-DPB11401, DPA10202-DPB12901, DPA10301-DPB10301, DPA10301- DPB110601, DPA10301-DPB15501, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401- DPB11401. [2073] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 1248, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10301, DPA10103-DPB10501, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB11901, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103- DPB15001, DPA10104-DPB10301, DPA10105-DPB10301, DPA10105-DPB15001, DPA10202-DPB11401, DPA10202-DPB12901, DPA10301-DPB10301, DPA10301- DPB110601, DPA10301-DPB15501, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401- DPB11401. [2074] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 1249, wherein a peptide with this - 417 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10301, DPA10103-DPB10501, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB11901, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103- DPB15001, DPA10104-DPB10301, DPA10105-DPB10301, DPA10105-DPB15001, DPA10202-DPB11401, DPA10202-DPB12901, DPA10301-DPB10301, DPA10301- DPB110601, DPA10301-DPB15501, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401- DPB11401. [2075] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 1250, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10301, DPA10103-DPB10501, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB11901, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103- DPB15001, DPA10104-DPB10301, DPA10105-DPB10301, DPA10105-DPB15001, DPA10202-DPB11401, DPA10202-DPB12901, DPA10301-DPB10301, DPA10301- DPB110601, DPA10301-DPB15501, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401- DPB11401. [2076] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 1251, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10301, DPA10103-DPB10501, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB11901, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103- DPB15001, DPA10104-DPB10301, DPA10105-DPB10301, DPA10105-DPB15001, DPA10202-DPB11401, DPA10202-DPB12901, DPA10301-DPB10301, DPA10301- DPB110601, DPA10301-DPB15501, DPA10401-DPB10101, DPA10401-DPB10301, - 418 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401- DPB11401. [2077] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 1252, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10301, DPA10103-DPB10501, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB11901, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103- DPB15001, DPA10104-DPB10301, DPA10105-DPB10301, DPA10105-DPB15001, DPA10202-DPB11401, DPA10202-DPB12901, DPA10301-DPB10301, DPA10301- DPB110601, DPA10301-DPB15501, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401- DPB11401. [2078] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 1253, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10103-DPB10301, DPA10103-DPB10501, DPA10103-DPB10601, DPA10103- DPB11101, DPA10103-DPB112401, DPA10103-DPB11401, DPA10103-DPB11601, DPA10103-DPB11901, DPA10103-DPB12001, DPA10103-DPB12901, DPA10103- DPB15001, DPA10104-DPB10301, DPA10105-DPB10301, DPA10105-DPB15001, DPA10202-DPB11401, DPA10202-DPB12901, DPA10301-DPB10301, DPA10301- DPB110601, DPA10301-DPB15501, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, DPA10401-DPB11301, DPA10401-DPB113301, and DPA10401- DPB11401. [2079] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 1254, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1301, DPA10103-DPB10301, DPA10103-DPB10501, DPA10103- DPB10601, DPA10103-DPB112401, DPA10103-DPB11601, DPA10103-DPB11901, - 419 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DPA10103-DPB12001, DPA10103-DPB13101, DPA10103-DPB15001, DPA10104- DPB10301, DPA10105-DPB10301, DPA10105-DPB15001, DPA10301-DPB110601, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, and DPA10401- DPB11401. [2080] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V157F protein mutation comprises SEQ ID NO: 1255, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102, DRB1_1301, DPA10103-DPB10301, DPA10103-DPB10501, DPA10103- DPB10601, DPA10103-DPB112401, DPA10103-DPB11601, DPA10103-DPB11901, DPA10103-DPB12001, DPA10103-DPB13101, DPA10103-DPB15001, DPA10104- DPB10301, DPA10105-DPB10301, DPA10105-DPB15001, DPA10301-DPB110601, DPA10401-DPB10101, DPA10401-DPB10301, DPA10401-DPB10501, and DPA10401- DPB11401. [2081] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 1256, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102 and DRB1_1301. [2082] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 1257, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102 and DRB1_1301. [2083] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 1258, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102 and DRB1_1301. [2084] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 V272M protein mutation comprises SEQ ID NO: 1259, wherein a peptide with this - 420 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1102 and DRB1_1301. [2085] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 1260, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0402, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1501, DPA10202-DPB10301, DPA10202-DPB11401, DPA10202-DPB14501, DQA10102-DQB10501, DQA10102- DQB10601, DQA10103-DQB10601, DQA10103-DQB10602, DQA10201-DQB10301, DQA10201-DQB10303, DQA10505-DQB10402, and DQA10506-DQB10303. [2086] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 1261, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1501, DPA10202-DPB11401, and DQA10505- DQB10402. [2087] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 1262, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0402, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1501, DPA10202-DPB10301, DPA10202-DPB11401, DPA10202-DPB14501, DQA10102-DQB10501, DQA10102- - 421 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 DQB10601, DQA10103-DQB10601, DQA10103-DQB10602, DQA10201-DQB10301, DQA10201-DQB10303, DQA10505-DQB10402, and DQA10506-DQB10303. [2088] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 1263, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1501, and DQA10505-DQB10402. [2089] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 1264, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0402, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1501, DPA10202-DPB10301, DPA10202-DPB11401, DPA10202-DPB14501, DQA10102-DQB10501, DQA10102- DQB10601, DQA10102-DQB10602, DQA10102-DQB10611, DQA10103-DQB10601, DQA10103-DQB10602, DQA10201-DQB10301, DQA10201-DQB10303, DQA10505- DQB10402, and DQA10506-DQB10303. [2090] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 1265, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_0410, DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1501, and DQA10505-DQB10402. [2091] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 1266, wherein a peptide with this - 422 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0402, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_0901, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DRB1_1501, DPA10202-DPB11401, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102-DQB10602, DQA10103- DQB10601, DQA10103-DQB10602, DQA10201-DQB10301, DQA10201-DQB10303, DQA10505-DQB10402, and DQA10506-DQB10303. [2092] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 1267, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0401, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_0801, DRB1_0802, DRB1_0804, DRB1_0806, DRB1_0809, DRB1_0813, DRB1_1001, DRB1_1101, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1305, DRB1_1406, DQA10102-DQB10501, DQA10102-DQB10601, DQA10102- DQB10602, DQA10102-DQB10611, DQA10103-DQB10601, DQA10103-DQB10602, and DQA10505-DQB10402. [2093] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 1268, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0102, DRB1_0404, DRB1_0405, DRB1_0408, DRB1_0410, DRB1_0806, DRB1_1001, DRB1_1102, DRB1_1103, DRB1_1104, DRB1_1301, DRB1_1304, DRB1_1406, DQA10102-DQB10501, DQA10103-DQB10601, and DQA10505-DQB10402. [2094] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y163C protein mutation comprises SEQ ID NO: 1269, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DQA10102-DQB10601, DQA10102-DQB10602, DQA10102-DQB10611, DQA10103- DQB10601, DQA10103-DQB10602, and DQA10505-DQB10402. - 423 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2095] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 1270, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1304, DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301- DPB14001, DPA10401-DPB10101, DPA10401-DPB10501, DQA10102-DQB10501, and DQA10103-DQB10501. [2096] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 1271, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB14001, DPA10401-DPB10101, and DPA10401-DPB10501. [2097] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 1272, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB14001, DPA10401-DPB10101, DPA10401-DPB10501, DQA10102-DQB10501, and DQA10103- DQB10501. [2098] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 1273, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_1304, DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301-DPB10202, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301- DPB14001, DPA10401-DPB10101, DPA10401-DPB10501, and DQA10103-DQB10501. [2099] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 1274, wherein a peptide with this - 424 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB14001, DPA10401-DPB10101, and DPA10401-DPB10501. [2100] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 1275, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB14001, DPA10401-DPB10101, and DPA10401-DPB10501. [2101] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 1276, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DPA10202-DPB10101, DPA10301-DPB10101, DPA10301-DPB10201, DPA10301- DPB10202, DPA10301-DPB110601, DPA10301-DPB11801, DPA10301-DPB14001, DPA10401-DPB10101, and DPA10401-DPB10501. [2102] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 1277, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101 and DRB1_1501. [2103] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 1278, wherein a peptide with this sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0405, DRB1_0410, DRB1_1001, and DRB1_1602. [2104] In some embodiments, the amino acid sequence for an MHC class II peptide vaccine for a TP53 Y205C protein mutation comprises SEQ ID NO: 1279, wherein a peptide with this - 425 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence is configured to bind in vivo to one or more HLA alleles present in a subject, and wherein the one or more HLA alleles present in the subject is selected from the group consisting of DRB1_0101, DRB1_0401, DRB1_0405, DRB1_0410, DRB1_1001, and DRB1_1602. MHC class II peptide sequences [2105] In some embodiments, a peptide composition (single target or combined multiple target) comprises about 1 to 40 MHC class II peptides with each peptide consisting of about 20 amino acids. In some embodiments, an MHC class II peptide composition is intended for one or more of the BRAF, CTNNB1, KRAS, PIK3CA, or TP53 mutated protein targets. In some embodiments, an MHC class II peptide composition is intended for one or more of the BRAF G466V, CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, CTNNB1 T41I, KRAS A146T, KRAS A146V, KRAS Q61H, PIK3CA C420R, PIK3CA E453K, PIK3CA E545A, PIK3CA E726K, PIK3CA G118D, PIK3CA H1047L, PIK3CA N345K, PIK3CA Q546K, PIK3CA Q546R, PIK3CA R108H, TP53 C176F, TP53 C176Y, TP53 C238Y, TP53 C275Y, TP53 E285K, TP53 G245S, TP53 G245V, TP53 H179Y, TP53 H193R, TP53 I195T, TP53 K132E, TP53 K132N, TP53 P151S, TP53 R213L, TP53 R249M, TP53 R249S, TP53 R273L, TP53 R280K, TP53 S127Y, TP53 S241F, TP53 V157F, TP53 V272M, TP53 Y163C, TP53 Y205C, or TP53 Y234C protein mutation targets. In some embodiments, an MHC class II peptide composition is intended to prevent cancer. In some embodiments, an MHC class II peptide composition is intended to treat cancer. [2106] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the BRAF protein comprises one or more of the SEQ ID NOs: 835 to 844. In some embodiments, any one of the peptides in the BRAF composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 835 to 844. [2107] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the BRAF protein comprises one or more of the SEQ ID NOs: 835 to 844, SEQ ID NOs: 36797 to 36907, and SEQ ID NOs: 60854 to 60863. In some embodiments, any one of the peptides in the BRAF composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 835 to 844, SEQ ID NOs: 36797 to 36907, or SEQ ID NOs: 60854 to 60863. - 426 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2108] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the BRAF protein comprises two or more of the SEQ ID NOs: 835 to 844. In some embodiments, any one of the peptides in the BRAF composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 835 to 844. [2109] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the BRAF protein comprises two or more of the SEQ ID NOs: 835 to 844, SEQ ID NOs: 36797 to 36907, and SEQ ID NOs: 60854 to 60863. In some embodiments, any one of the peptides in the BRAF composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 835 to 844, SEQ ID NOs: 36797 to 36907, or SEQ ID NOs: 60854 to 60863. [2110] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the CTNNB1 protein comprises one or more of the SEQ ID NOs: 845 to 935. In some embodiments, any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 845 to 935. [2111] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the CTNNB1 protein comprises one or more of the SEQ ID NOs: 845 to 935, SEQ ID NOs: 36908 to 40038, and SEQ ID NOs: 60864 to 60946. In some embodiments, any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 845 to 935, SEQ ID NOs: 36908 to 40038, or SEQ ID NOs: 60864 to 60946. [2112] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the CTNNB1 protein comprises two or more of the SEQ ID NOs: 845 to 935. In some embodiments, any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 845 to 935. [2113] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the CTNNB1 protein comprises two or more of the SEQ ID NOs: - 427 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 845 to 935, SEQ ID NOs: 36908 to 40038, and SEQ ID NOs: 60864 to 60946. In some embodiments, any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 845 to 935, SEQ ID NOs: 36908 to 40038, or SEQ ID NOs: 60864 to 60946. [2114] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the KRAS protein comprises one or more of the SEQ ID NOs: 936 to 965. In some embodiments, any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 936 to 965. [2115] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the KRAS protein comprises one or more of the SEQ ID NOs: 936 to 965, SEQ ID NOs: 40039 to 43494, and SEQ ID NOs: 60947 to 60976. In some embodiments, any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 936 to 965, SEQ ID NOs: 40039 to 43494, or SEQ ID NOs: 60947 to 60976. [2116] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the KRAS protein comprises two or more of the SEQ ID NOs: 936 to 965. In some embodiments, any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 936 to 965. [2117] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the KRAS protein comprises two or more of the SEQ ID NOs: 936 to 965, SEQ ID NOs: 40039 to 43494, and SEQ ID NOs: 60947 to 60976. In some embodiments, any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 936 to 965, SEQ ID NOs: 40039 to 43494, or SEQ ID NOs: 60947 to 60976. [2118] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the PIK3CA protein comprises one or more of the SEQ ID NOs: - 428 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 966 to 1065. In some embodiments, any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 966 to 1065. [2119] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the PIK3CA protein comprises one or more of the SEQ ID NOs: 966 to 1065, SEQ ID NOs: 43495 to 49560, and SEQ ID NOs: 60977 to 61069. In some embodiments, any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 966 to 1065, SEQ ID NOs: 43495 to 49560, or SEQ ID NOs: 60977 to 61069. [2120] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the PIK3CA protein comprises two or more of the SEQ ID NOs: 966 to 1065. In some embodiments, any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 966 to 1065. [2121] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the PIK3CA protein comprises two or more of the SEQ ID NOs: 966 to 1065, SEQ ID NOs: 43495 to 49560, and SEQ ID NOs: 60977 to 61069. In some embodiments, any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 966 to 1065, SEQ ID NOs: 43495 to 49560, or SEQ ID NOs: 60977 to 61069. [2122] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the TP53 protein comprises one or more of the SEQ ID NOs: 1066 to 1279. In some embodiments, any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1066 to 1279. [2123] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the TP53 protein comprises one or more of the SEQ ID NOs: 1066 to 1279, SEQ ID NOs: 49561 to 60853, and SEQ ID NOs: 61070 to 61281. In some embodiments, any one of the peptides in the TP53 composition comprise an amino acid - 429 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1066 to 1279, SEQ ID NOs: 49561 to 60853, or SEQ ID NOs: 61070 to 61281. [2124] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the TP53 protein comprises two or more of the SEQ ID NOs: 1066 to 1279. In some embodiments, any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1066 to 1279. [2125] In some embodiments, the amino acid sequence for a MHC class II peptide composition for mutation in the TP53 protein comprises two or more of the SEQ ID NOs: 1066 to 1279, SEQ ID NOs: 49561 to 60853, and SEQ ID NOs: 61070 to 61281. In some embodiments, any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1066 to 1279, SEQ ID NOs: 49561 to 60853, or SEQ ID NOs: 61070 to 61281. [2126] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the BRAF G466V protein mutation comprises one or more of the SEQ ID NOs: 835 to 844. In some embodiments, any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 835 to 844. [2127] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the BRAF G466V protein mutation comprises one or more of the SEQ ID NOs: 835 to 844, SEQ ID NOs: 36797 to 36907, and SEQ ID NOs: 60854 to 60863. In some embodiments, any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 835 to 844, SEQ ID NOs: 36797 to 36907, or SEQ ID NOs: 60854 to 60863. [2128] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the BRAF G466V protein mutation comprises two or more of the SEQ ID NOs: 835 to 844. In some embodiments, any one of the peptides in the BRAF G466V composition - 430 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 835 to 844. [2129] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the BRAF G466V protein mutation comprises two or more of the SEQ ID NOs: 835 to 844, SEQ ID NOs: 36797 to 36907, and SEQ ID NOs: 60854 to 60863. In some embodiments, any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 835 to 844, SEQ ID NOs: 36797 to 36907, or SEQ ID NOs: 60854 to 60863. [2130] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 D32G protein mutation comprises one or more of the SEQ ID NOs: 845 to 854. In some embodiments, any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 845 to 854. [2131] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 D32G protein mutation comprises one or more of the SEQ ID NOs: 845 to 854, SEQ ID NOs: 36908 to 37076, and SEQ ID NOs: 60864 to 60872. In some embodiments, any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 845 to 854, SEQ ID NOs: 36908 to 37076, or SEQ ID NOs: 60864 to 60872. [2132] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 D32G protein mutation comprises two or more of the SEQ ID NOs: 845 to 854. In some embodiments, any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 845 to 854. [2133] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 D32G protein mutation comprises two or more of the SEQ ID NOs: 845 to 854, SEQ ID NOs: 36908 to 37076, and SEQ ID NOs: 60864 to 60872. In some embodiments, any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 431 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 identical to SEQ ID NOs: 845 to 854, SEQ ID NOs: 36908 to 37076, or SEQ ID NOs: 60864 to 60872. [2134] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 G34E protein mutation comprises one or more of the SEQ ID NOs: 855 to 864. In some embodiments, any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 855 to 864. [2135] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 G34E protein mutation comprises one or more of the SEQ ID NOs: 855 to 864, SEQ ID NOs: 37077 to 37185, and SEQ ID NOs: 60873 to 60882. In some embodiments, any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 855 to 864, SEQ ID NOs: 37077 to 37185, or SEQ ID NOs: 60873 to 60882. [2136] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 G34E protein mutation comprises two or more of the SEQ ID NOs: 855 to 864. In some embodiments, any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 855 to 864. [2137] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 G34E protein mutation comprises two or more of the SEQ ID NOs: 855 to 864, SEQ ID NOs: 37077 to 37185, and SEQ ID NOs: 60873 to 60882. In some embodiments, any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 855 to 864, SEQ ID NOs: 37077 to 37185, or SEQ ID NOs: 60873 to 60882. [2138] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S33C protein mutation comprises one or more of the SEQ ID NO: 865. In some embodiments, any one of the peptides in the CTNNB1 S33C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 865. - 432 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2139] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S33C protein mutation comprises one or more of the SEQ ID NO: 865, SEQ ID NOs: 37186 to 37234, and SEQ ID NO: 60883. In some embodiments, any one of the peptides in the CTNNB1 S33C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 865, SEQ ID NOs: 37186 to 37234, or SEQ ID NO: 60883. [2140] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S33C protein mutation comprises two or more of the SEQ ID NO: 865. In some embodiments, any one of the peptides in the CTNNB1 S33C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 865. [2141] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S33C protein mutation comprises two or more of the SEQ ID NO: 865, SEQ ID NOs: 37186 to 37234, and SEQ ID NO: 60883. In some embodiments, any one of the peptides in the CTNNB1 S33C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 865, SEQ ID NOs: 37186 to 37234, or SEQ ID NO: 60883. [2142] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S33F protein mutation comprises one or more of the SEQ ID NOs: 866 to 875. In some embodiments, any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 866 to 875. [2143] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S33F protein mutation comprises one or more of the SEQ ID NOs: 866 to 875, SEQ ID NOs: 37235 to 37344, and SEQ ID NOs: 60884 to 60891. In some embodiments, any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 866 to 875, SEQ ID NOs: 37235 to 37344, or SEQ ID NOs: 60884 to 60891. [2144] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S33F protein mutation comprises two or more of the SEQ ID - 433 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 NOs: 866 to 875. In some embodiments, any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 866 to 875. [2145] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S33F protein mutation comprises two or more of the SEQ ID NOs: 866 to 875, SEQ ID NOs: 37235 to 37344, and SEQ ID NOs: 60884 to 60891. In some embodiments, any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 866 to 875, SEQ ID NOs: 37235 to 37344, or SEQ ID NOs: 60884 to 60891. [2146] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S37C protein mutation comprises one or more of the SEQ ID NOs: 876 to 885. In some embodiments, any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 876 to 885. [2147] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S37C protein mutation comprises one or more of the SEQ ID NOs: 876 to 885, SEQ ID NOs: 37345 to 37456, and SEQ ID NOs: 60892 to 60899. In some embodiments, any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 876 to 885, SEQ ID NOs: 37345 to 37456, or SEQ ID NOs: 60892 to 60899. [2148] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S37C protein mutation comprises two or more of the SEQ ID NOs: 876 to 885. In some embodiments, any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 876 to 885. [2149] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S37C protein mutation comprises two or more of the SEQ ID NOs: 876 to 885, SEQ ID NOs: 37345 to 37456, and SEQ ID NOs: 60892 to 60899. In some embodiments, any one of the peptides in the CTNNB1 S37C composition comprise an amino - 434 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 876 to 885, SEQ ID NOs: 37345 to 37456, or SEQ ID NOs: 60892 to 60899. [2150] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S37F protein mutation comprises one or more of the SEQ ID NOs: 886 to 895. In some embodiments, any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 886 to 895. [2151] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S37F protein mutation comprises one or more of the SEQ ID NOs: 886 to 895, SEQ ID NOs: 37457 to 38596, and SEQ ID NOs: 60900 to 60908. In some embodiments, any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 886 to 895, SEQ ID NOs: 37457 to 38596, or SEQ ID NOs: 60900 to 60908. [2152] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S37F protein mutation comprises two or more of the SEQ ID NOs: 886 to 895. In some embodiments, any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 886 to 895. [2153] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S37F protein mutation comprises two or more of the SEQ ID NOs: 886 to 895, SEQ ID NOs: 37457 to 38596, and SEQ ID NOs: 60900 to 60908. In some embodiments, any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 886 to 895, SEQ ID NOs: 37457 to 38596, or SEQ ID NOs: 60900 to 60908. [2154] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S45F protein mutation comprises one or more of the SEQ ID NOs: 896 to 905. In some embodiments, any one of the peptides in the CTNNB1 S45F - 435 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 896 to 905. [2155] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S45F protein mutation comprises one or more of the SEQ ID NOs: 896 to 905, SEQ ID NOs: 38597 to 38651, and SEQ ID NOs: 60909 to 60917. In some embodiments, any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 896 to 905, SEQ ID NOs: 38597 to 38651, or SEQ ID NOs: 60909 to 60917. [2156] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S45F protein mutation comprises two or more of the SEQ ID NOs: 896 to 905. In some embodiments, any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 896 to 905. [2157] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S45F protein mutation comprises two or more of the SEQ ID NOs: 896 to 905, SEQ ID NOs: 38597 to 38651, and SEQ ID NOs: 60909 to 60917. In some embodiments, any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 896 to 905, SEQ ID NOs: 38597 to 38651, or SEQ ID NOs: 60909 to 60917. [2158] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S45P protein mutation comprises one or more of the SEQ ID NOs: 906 to 915. In some embodiments, any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 906 to 915. [2159] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S45P protein mutation comprises one or more of the SEQ ID NOs: 906 to 915, SEQ ID NOs: 38652 to 38686, and SEQ ID NOs: 60918 to 60927. In some embodiments, any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 436 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 identical to SEQ ID NOs: 906 to 915, SEQ ID NOs: 38652 to 38686, or SEQ ID NOs: 60918 to 60927. [2160] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S45P protein mutation comprises two or more of the SEQ ID NOs: 906 to 915. In some embodiments, any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 906 to 915. [2161] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 S45P protein mutation comprises two or more of the SEQ ID NOs: 906 to 915, SEQ ID NOs: 38652 to 38686, and SEQ ID NOs: 60918 to 60927. In some embodiments, any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 906 to 915, SEQ ID NOs: 38652 to 38686, or SEQ ID NOs: 60918 to 60927. [2162] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 T41A protein mutation comprises one or more of the SEQ ID NOs: 916 to 925. In some embodiments, any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 916 to 925. [2163] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 T41A protein mutation comprises one or more of the SEQ ID NOs: 916 to 925, SEQ ID NOs: 38687 to 38944, and SEQ ID NOs: 60928 to 60936. In some embodiments, any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 916 to 925, SEQ ID NOs: 38687 to 38944, or SEQ ID NOs: 60928 to 60936. [2164] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 T41A protein mutation comprises two or more of the SEQ ID NOs: 916 to 925. In some embodiments, any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 916 to 925. - 437 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2165] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 T41A protein mutation comprises two or more of the SEQ ID NOs: 916 to 925, SEQ ID NOs: 38687 to 38944, and SEQ ID NOs: 60928 to 60936. In some embodiments, any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 916 to 925, SEQ ID NOs: 38687 to 38944, or SEQ ID NOs: 60928 to 60936. [2166] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 T41I protein mutation comprises one or more of the SEQ ID NOs: 926 to 935. In some embodiments, any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 926 to 935. [2167] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 T41I protein mutation comprises one or more of the SEQ ID NOs: 926 to 935, SEQ ID NOs: 38945 to 40038, and SEQ ID NOs: 60937 to 60946. In some embodiments, any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 926 to 935, SEQ ID NOs: 38945 to 40038, or SEQ ID NOs: 60937 to 60946. [2168] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 T41I protein mutation comprises two or more of the SEQ ID NOs: 926 to 935. In some embodiments, any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 926 to 935. [2169] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the CTNNB1 T41I protein mutation comprises two or more of the SEQ ID NOs: 926 to 935, SEQ ID NOs: 38945 to 40038, and SEQ ID NOs: 60937 to 60946. In some embodiments, any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 926 to 935, SEQ ID NOs: 38945 to 40038, or SEQ ID NOs: 60937 to 60946. - 438 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2170] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS A146T protein mutation comprises one or more of the SEQ ID NOs: 936 to 945. In some embodiments, any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 936 to 945. [2171] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS A146T protein mutation comprises one or more of the SEQ ID NOs: 936 to 945, SEQ ID NOs: 40039 to 40142, and SEQ ID NOs: 60947 to 60956. In some embodiments, any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 936 to 945, SEQ ID NOs: 40039 to 40142, or SEQ ID NOs: 60947 to 60956. [2172] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS A146T protein mutation comprises two or more of the SEQ ID NOs: 936 to 945. In some embodiments, any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 936 to 945. [2173] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS A146T protein mutation comprises two or more of the SEQ ID NOs: 936 to 945, SEQ ID NOs: 40039 to 40142, and SEQ ID NOs: 60947 to 60956. In some embodiments, any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 936 to 945, SEQ ID NOs: 40039 to 40142, or SEQ ID NOs: 60947 to 60956. [2174] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS A146V protein mutation comprises one or more of the SEQ ID NOs: 946 to 955. In some embodiments, any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 946 to 955. [2175] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS A146V protein mutation comprises one or more of the SEQ ID NOs: - 439 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 946 to 955, SEQ ID NOs: 40143 to 43468, and SEQ ID NOs: 60957 to 60966. In some embodiments, any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 946 to 955, SEQ ID NOs: 40143 to 43468, or SEQ ID NOs: 60957 to 60966. [2176] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS A146V protein mutation comprises two or more of the SEQ ID NOs: 946 to 955. In some embodiments, any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 946 to 955. [2177] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS A146V protein mutation comprises two or more of the SEQ ID NOs: 946 to 955, SEQ ID NOs: 40143 to 43468, and SEQ ID NOs: 60957 to 60966. In some embodiments, any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 946 to 955, SEQ ID NOs: 40143 to 43468, or SEQ ID NOs: 60957 to 60966. [2178] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS Q61H protein mutation comprises one or more of the SEQ ID NOs: 956 to 965. In some embodiments, any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 956 to 965. [2179] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS Q61H protein mutation comprises one or more of the SEQ ID NOs: 956 to 965, SEQ ID NOs: 43469 to 43494, and SEQ ID NOs: 60967 to 60976. In some embodiments, any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 956 to 965, SEQ ID NOs: 43469 to 43494, or SEQ ID NOs: 60967 to 60976. [2180] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS Q61H protein mutation comprises two or more of the SEQ ID NOs: - 440 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 956 to 965. In some embodiments, any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 956 to 965. [2181] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the KRAS Q61H protein mutation comprises two or more of the SEQ ID NOs: 956 to 965, SEQ ID NOs: 43469 to 43494, and SEQ ID NOs: 60967 to 60976. In some embodiments, any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 956 to 965, SEQ ID NOs: 43469 to 43494, or SEQ ID NOs: 60967 to 60976. [2182] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA C420R protein mutation comprises one or more of the SEQ ID NOs: 966 to 975. In some embodiments, any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 966 to 975. [2183] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA C420R protein mutation comprises one or more of the SEQ ID NOs: 966 to 975, SEQ ID NOs: 43495 to 43802, and SEQ ID NOs: 60977 to 60985. In some embodiments, any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 966 to 975, SEQ ID NOs: 43495 to 43802, or SEQ ID NOs: 60977 to 60985. [2184] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA C420R protein mutation comprises two or more of the SEQ ID NOs: 966 to 975. In some embodiments, any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 966 to 975. [2185] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA C420R protein mutation comprises two or more of the SEQ ID NOs: 966 to 975, SEQ ID NOs: 43495 to 43802, and SEQ ID NOs: 60977 to 60985. In some embodiments, any one of the peptides in the PIK3CA C420R composition comprise an amino - 441 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 966 to 975, SEQ ID NOs: 43495 to 43802, or SEQ ID NOs: 60977 to 60985. [2186] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E453K protein mutation comprises one or more of the SEQ ID NOs: 976 to 985. In some embodiments, any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 976 to 985. [2187] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E453K protein mutation comprises one or more of the SEQ ID NOs: 976 to 985, SEQ ID NOs: 43803 to 43939, and SEQ ID NOs: 60986 to 60995. In some embodiments, any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 976 to 985, SEQ ID NOs: 43803 to 43939, or SEQ ID NOs: 60986 to 60995. [2188] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E453K protein mutation comprises two or more of the SEQ ID NOs: 976 to 985. In some embodiments, any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 976 to 985. [2189] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E453K protein mutation comprises two or more of the SEQ ID NOs: 976 to 985, SEQ ID NOs: 43803 to 43939, and SEQ ID NOs: 60986 to 60995. In some embodiments, any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 976 to 985, SEQ ID NOs: 43803 to 43939, or SEQ ID NOs: 60986 to 60995. [2190] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E545A protein mutation comprises one or more of the SEQ ID NOs: 986 to 995. In some embodiments, any one of the peptides in the PIK3CA E545A - 442 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 986 to 995. [2191] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E545A protein mutation comprises one or more of the SEQ ID NOs: 986 to 995, SEQ ID NOs: 43940 to 43970, and SEQ ID NOs: 60996 to 61004. In some embodiments, any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 986 to 995, SEQ ID NOs: 43940 to 43970, or SEQ ID NOs: 60996 to 61004. [2192] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E545A protein mutation comprises two or more of the SEQ ID NOs: 986 to 995. In some embodiments, any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 986 to 995. [2193] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E545A protein mutation comprises two or more of the SEQ ID NOs: 986 to 995, SEQ ID NOs: 43940 to 43970, and SEQ ID NOs: 60996 to 61004. In some embodiments, any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 986 to 995, SEQ ID NOs: 43940 to 43970, or SEQ ID NOs: 60996 to 61004. [2194] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E726K protein mutation comprises one or more of the SEQ ID NOs: 996 to 1005. In some embodiments, any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 996 to 1005. [2195] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E726K protein mutation comprises one or more of the SEQ ID NOs: 996 to 1005, SEQ ID NOs: 43971 to 47907, and SEQ ID NOs: 61005 to 61014. In some embodiments, any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 443 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 identical to SEQ ID NOs: 996 to 1005, SEQ ID NOs: 43971 to 47907, or SEQ ID NOs: 61005 to 61014. [2196] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E726K protein mutation comprises two or more of the SEQ ID NOs: 996 to 1005. In some embodiments, any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 996 to 1005. [2197] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA E726K protein mutation comprises two or more of the SEQ ID NOs: 996 to 1005, SEQ ID NOs: 43971 to 47907, and SEQ ID NOs: 61005 to 61014. In some embodiments, any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 996 to 1005, SEQ ID NOs: 43971 to 47907, or SEQ ID NOs: 61005 to 61014. [2198] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA G118D protein mutation comprises one or more of the SEQ ID NOs: 1006 to 1015. In some embodiments, any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1006 to 1015. [2199] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA G118D protein mutation comprises one or more of the SEQ ID NOs: 1006 to 1015, SEQ ID NOs: 47908 to 48313, and SEQ ID NOs: 61015 to 61024. In some embodiments, any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1006 to 1015, SEQ ID NOs: 47908 to 48313, or SEQ ID NOs: 61015 to 61024. [2200] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA G118D protein mutation comprises two or more of the SEQ ID NOs: 1006 to 1015. In some embodiments, any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1006 to 1015. - 444 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2201] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA G118D protein mutation comprises two or more of the SEQ ID NOs: 1006 to 1015, SEQ ID NOs: 47908 to 48313, and SEQ ID NOs: 61015 to 61024. In some embodiments, any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1006 to 1015, SEQ ID NOs: 47908 to 48313, or SEQ ID NOs: 61015 to 61024. [2202] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA H1047L protein mutation comprises one or more of the SEQ ID NOs: 1016 to 1025. In some embodiments, any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1016 to 1025. [2203] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA H1047L protein mutation comprises one or more of the SEQ ID NOs: 1016 to 1025, SEQ ID NOs: 48314 to 49032, and SEQ ID NOs: 61025 to 61034. In some embodiments, any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1016 to 1025, SEQ ID NOs: 48314 to 49032, or SEQ ID NOs: 61025 to 61034. [2204] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA H1047L protein mutation comprises two or more of the SEQ ID NOs: 1016 to 1025. In some embodiments, any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1016 to 1025. [2205] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA H1047L protein mutation comprises two or more of the SEQ ID NOs: 1016 to 1025, SEQ ID NOs: 48314 to 49032, and SEQ ID NOs: 61025 to 61034. In some embodiments, any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1016 to 1025, SEQ ID NOs: 48314 to 49032, or SEQ ID NOs: 61025 to 61034. - 445 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2206] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA N345K protein mutation comprises one or more of the SEQ ID NOs: 1026 to 1035. In some embodiments, any one of the peptides in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1026 to 1035. [2207] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA N345K protein mutation comprises one or more of the SEQ ID NOs: 1026 to 1035, SEQ ID NOs: 49033 to 49385, and SEQ ID NOs: 61035 to 61044. In some embodiments, any one of the peptides in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1026 to 1035, SEQ ID NOs: 49033 to 49385, or SEQ ID NOs: 61035 to 61044. [2208] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA N345K protein mutation comprises two or more of the SEQ ID NOs: 1026 to 1035. In some embodiments, any one of the peptides in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1026 to 1035. [2209] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA N345K protein mutation comprises two or more of the SEQ ID NOs: 1026 to 1035, SEQ ID NOs: 49033 to 49385, and SEQ ID NOs: 61035 to 61044. In some embodiments, any one of the peptides in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1026 to 1035, SEQ ID NOs: 49033 to 49385, or SEQ ID NOs: 61035 to 61044. [2210] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA Q546K protein mutation comprises one or more of the SEQ ID NOs: 1036 to 1045. In some embodiments, any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1036 to 1045. [2211] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA Q546K protein mutation comprises one or more of the SEQ ID - 446 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 NOs: 1036 to 1045, SEQ ID NOs: 49386 to 49421, and SEQ ID NOs: 61045 to 61051. In some embodiments, any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1036 to 1045, SEQ ID NOs: 49386 to 49421, or SEQ ID NOs: 61045 to 61051. [2212] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA Q546K protein mutation comprises two or more of the SEQ ID NOs: 1036 to 1045. In some embodiments, any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1036 to 1045. [2213] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA Q546K protein mutation comprises two or more of the SEQ ID NOs: 1036 to 1045, SEQ ID NOs: 49386 to 49421, and SEQ ID NOs: 61045 to 61051. In some embodiments, any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1036 to 1045, SEQ ID NOs: 49386 to 49421, or SEQ ID NOs: 61045 to 61051. [2214] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA Q546R protein mutation comprises one or more of the SEQ ID NOs: 1046 to 1055. In some embodiments, any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1046 to 1055. [2215] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA Q546R protein mutation comprises one or more of the SEQ ID NOs: 1046 to 1055, SEQ ID NOs: 49422 to 49471, and SEQ ID NOs: 61052 to 61059. In some embodiments, any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1046 to 1055, SEQ ID NOs: 49422 to 49471, or SEQ ID NOs: 61052 to 61059. [2216] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA Q546R protein mutation comprises two or more of the SEQ ID - 447 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 NOs: 1046 to 1055. In some embodiments, any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1046 to 1055. [2217] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA Q546R protein mutation comprises two or more of the SEQ ID NOs: 1046 to 1055, SEQ ID NOs: 49422 to 49471, and SEQ ID NOs: 61052 to 61059. In some embodiments, any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1046 to 1055, SEQ ID NOs: 49422 to 49471, or SEQ ID NOs: 61052 to 61059. [2218] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA R108H protein mutation comprises one or more of the SEQ ID NOs: 1056 to 1065. In some embodiments, any one of the peptides in the PIK3CA R108H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1056 to 1065. [2219] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA R108H protein mutation comprises one or more of the SEQ ID NOs: 1056 to 1065, SEQ ID NOs: 49472 to 49560, and SEQ ID NOs: 61060 to 61069. In some embodiments, any one of the peptides in the PIK3CA R108H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1056 to 1065, SEQ ID NOs: 49472 to 49560, or SEQ ID NOs: 61060 to 61069. [2220] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA R108H protein mutation comprises two or more of the SEQ ID NOs: 1056 to 1065. In some embodiments, any one of the peptides in the PIK3CA R108H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1056 to 1065. [2221] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the PIK3CA R108H protein mutation comprises two or more of the SEQ ID NOs: 1056 to 1065, SEQ ID NOs: 49472 to 49560, and SEQ ID NOs: 61060 to 61069. In some embodiments, any one of the peptides in the PIK3CA R108H composition comprise an amino - 448 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1056 to 1065, SEQ ID NOs: 49472 to 49560, or SEQ ID NOs: 61060 to 61069. [2222] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C176F protein mutation comprises one or more of the SEQ ID NOs: 1066 to 1075. In some embodiments, any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1066 to 1075. [2223] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C176F protein mutation comprises one or more of the SEQ ID NOs: 1066 to 1075, SEQ ID NOs: 49561 to 49621, and SEQ ID NOs: 61070 to 61079. In some embodiments, any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1066 to 1075, SEQ ID NOs: 49561 to 49621, or SEQ ID NOs: 61070 to 61079. [2224] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C176F protein mutation comprises two or more of the SEQ ID NOs: 1066 to 1075. In some embodiments, any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1066 to 1075. [2225] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C176F protein mutation comprises two or more of the SEQ ID NOs: 1066 to 1075, SEQ ID NOs: 49561 to 49621, and SEQ ID NOs: 61070 to 61079. In some embodiments, any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1066 to 1075, SEQ ID NOs: 49561 to 49621, or SEQ ID NOs: 61070 to 61079. [2226] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C176Y protein mutation comprises one or more of the SEQ ID NOs: 1076 to 1085. In some embodiments, any one of the peptides in the TP53 C176Y composition - 449 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1076 to 1085. [2227] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C176Y protein mutation comprises one or more of the SEQ ID NOs: 1076 to 1085, SEQ ID NOs: 49622 to 49675, and SEQ ID NOs: 61080 to 61089. In some embodiments, any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1076 to 1085, SEQ ID NOs: 49622 to 49675, or SEQ ID NOs: 61080 to 61089. [2228] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C176Y protein mutation comprises two or more of the SEQ ID NOs: 1076 to 1085. In some embodiments, any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1076 to 1085. [2229] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C176Y protein mutation comprises two or more of the SEQ ID NOs: 1076 to 1085, SEQ ID NOs: 49622 to 49675, and SEQ ID NOs: 61080 to 61089. In some embodiments, any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1076 to 1085, SEQ ID NOs: 49622 to 49675, or SEQ ID NOs: 61080 to 61089. [2230] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C238Y protein mutation comprises one or more of the SEQ ID NOs: 1086 to 1095. In some embodiments, any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1086 to 1095. [2231] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C238Y protein mutation comprises one or more of the SEQ ID NOs: 1086 to 1095, SEQ ID NOs: 49676 to 50263, and SEQ ID NOs: 61090 to 61099. In some embodiments, any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 450 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 identical to SEQ ID NOs: 1086 to 1095, SEQ ID NOs: 49676 to 50263, or SEQ ID NOs: 61090 to 61099. [2232] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C238Y protein mutation comprises two or more of the SEQ ID NOs: 1086 to 1095. In some embodiments, any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1086 to 1095. [2233] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C238Y protein mutation comprises two or more of the SEQ ID NOs: 1086 to 1095, SEQ ID NOs: 49676 to 50263, and SEQ ID NOs: 61090 to 61099. In some embodiments, any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1086 to 1095, SEQ ID NOs: 49676 to 50263, or SEQ ID NOs: 61090 to 61099. [2234] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C275Y protein mutation comprises one or more of the SEQ ID NOs: 1096 to 1105. In some embodiments, any one of the peptides in the TP53 C275Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1096 to 1105. [2235] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C275Y protein mutation comprises one or more of the SEQ ID NOs: 1096 to 1105, SEQ ID NOs: 50264 to 50368, and SEQ ID NOs: 61100 to 61109. In some embodiments, any one of the peptides in the TP53 C275Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1096 to 1105, SEQ ID NOs: 50264 to 50368, or SEQ ID NOs: 61100 to 61109. [2236] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C275Y protein mutation comprises two or more of the SEQ ID NOs: 1096 to 1105. In some embodiments, any one of the peptides in the TP53 C275Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1096 to 1105. - 451 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2237] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 C275Y protein mutation comprises two or more of the SEQ ID NOs: 1096 to 1105, SEQ ID NOs: 50264 to 50368, and SEQ ID NOs: 61100 to 61109. In some embodiments, any one of the peptides in the TP53 C275Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1096 to 1105, SEQ ID NOs: 50264 to 50368, or SEQ ID NOs: 61100 to 61109. [2238] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 G245S protein mutation comprises one or more of the SEQ ID NOs: 1106 to 1115. In some embodiments, any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1106 to 1115. [2239] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 G245S protein mutation comprises one or more of the SEQ ID NOs: 1106 to 1115, SEQ ID NOs: 50369 to 50579, and SEQ ID NOs: 61110 to 61119. In some embodiments, any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1106 to 1115, SEQ ID NOs: 50369 to 50579, or SEQ ID NOs: 61110 to 61119. [2240] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 G245S protein mutation comprises two or more of the SEQ ID NOs: 1106 to 1115. In some embodiments, any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1106 to 1115. [2241] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 G245S protein mutation comprises two or more of the SEQ ID NOs: 1106 to 1115, SEQ ID NOs: 50369 to 50579, and SEQ ID NOs: 61110 to 61119. In some embodiments, any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1106 to 1115, SEQ ID NOs: 50369 to 50579, or SEQ ID NOs: 61110 to 61119. - 452 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2242] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 G245V protein mutation comprises one or more of the SEQ ID NOs: 1116 to 1125. In some embodiments, any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1116 to 1125. [2243] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 G245V protein mutation comprises one or more of the SEQ ID NOs: 1116 to 1125, SEQ ID NOs: 50580 to 50709, and SEQ ID NOs: 61120 to 61129. In some embodiments, any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1116 to 1125, SEQ ID NOs: 50580 to 50709, or SEQ ID NOs: 61120 to 61129. [2244] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 G245V protein mutation comprises two or more of the SEQ ID NOs: 1116 to 1125. In some embodiments, any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1116 to 1125. [2245] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 G245V protein mutation comprises two or more of the SEQ ID NOs: 1116 to 1125, SEQ ID NOs: 50580 to 50709, and SEQ ID NOs: 61120 to 61129. In some embodiments, any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1116 to 1125, SEQ ID NOs: 50580 to 50709, or SEQ ID NOs: 61120 to 61129. [2246] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 H179Y protein mutation comprises one or more of the SEQ ID NOs: 1126 to 1135. In some embodiments, any one of the peptides in the TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1126 to 1135. [2247] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 H179Y protein mutation comprises one or more of the SEQ ID NOs: - 453 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 1126 to 1135, SEQ ID NOs: 50710 to 50755, and SEQ ID NOs: 61130 to 61139. In some embodiments, any one of the peptides in the TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1126 to 1135, SEQ ID NOs: 50710 to 50755, or SEQ ID NOs: 61130 to 61139. [2248] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 H179Y protein mutation comprises two or more of the SEQ ID NOs: 1126 to 1135. In some embodiments, any one of the peptides in the TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1126 to 1135. [2249] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 H179Y protein mutation comprises two or more of the SEQ ID NOs: 1126 to 1135, SEQ ID NOs: 50710 to 50755, and SEQ ID NOs: 61130 to 61139. In some embodiments, any one of the peptides in the TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1126 to 1135, SEQ ID NOs: 50710 to 50755, or SEQ ID NOs: 61130 to 61139. [2250] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 H193R protein mutation comprises one or more of the SEQ ID NOs: 1136 to 1145. In some embodiments, any one of the peptides in the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1136 to 1145. [2251] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 H193R protein mutation comprises one or more of the SEQ ID NOs: 1136 to 1145, SEQ ID NOs: 50756 to 51569, and SEQ ID NOs: 61140 to 61149. In some embodiments, any one of the peptides in the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1136 to 1145, SEQ ID NOs: 50756 to 51569, or SEQ ID NOs: 61140 to 61149. [2252] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 H193R protein mutation comprises two or more of the SEQ ID NOs: - 454 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 1136 to 1145. In some embodiments, any one of the peptides in the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1136 to 1145. [2253] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 H193R protein mutation comprises two or more of the SEQ ID NOs: 1136 to 1145, SEQ ID NOs: 50756 to 51569, and SEQ ID NOs: 61140 to 61149. In some embodiments, any one of the peptides in the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1136 to 1145, SEQ ID NOs: 50756 to 51569, or SEQ ID NOs: 61140 to 61149. [2254] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 I195T protein mutation comprises one or more of the SEQ ID NOs: 1146 to 1155. In some embodiments, any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1146 to 1155. [2255] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 I195T protein mutation comprises one or more of the SEQ ID NOs: 1146 to 1155, SEQ ID NOs: 51570 to 53061, and SEQ ID NOs: 61150 to 61159. In some embodiments, any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1146 to 1155, SEQ ID NOs: 51570 to 53061, or SEQ ID NOs: 61150 to 61159. [2256] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 I195T protein mutation comprises two or more of the SEQ ID NOs: 1146 to 1155. In some embodiments, any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1146 to 1155. [2257] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 I195T protein mutation comprises two or more of the SEQ ID NOs: 1146 to 1155, SEQ ID NOs: 51570 to 53061, and SEQ ID NOs: 61150 to 61159. In some embodiments, any one of the peptides in the TP53 I195T composition comprise an amino acid - 455 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1146 to 1155, SEQ ID NOs: 51570 to 53061, or SEQ ID NOs: 61150 to 61159. [2258] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 K132E protein mutation comprises one or more of the SEQ ID NOs: 1156 to 1165. In some embodiments, any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1156 to 1165. [2259] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 K132E protein mutation comprises one or more of the SEQ ID NOs: 1156 to 1165, SEQ ID NOs: 53062 to 53249, and SEQ ID NOs: 61160 to 61168. In some embodiments, any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1156 to 1165, SEQ ID NOs: 53062 to 53249, or SEQ ID NOs: 61160 to 61168. [2260] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 K132E protein mutation comprises two or more of the SEQ ID NOs: 1156 to 1165. In some embodiments, any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1156 to 1165. [2261] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 K132E protein mutation comprises two or more of the SEQ ID NOs: 1156 to 1165, SEQ ID NOs: 53062 to 53249, and SEQ ID NOs: 61160 to 61168. In some embodiments, any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1156 to 1165, SEQ ID NOs: 53062 to 53249, or SEQ ID NOs: 61160 to 61168. [2262] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 K132N protein mutation comprises one or more of the SEQ ID NOs: 1166 to 1175. In some embodiments, any one of the peptides in the TP53 K132N composition - 456 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1166 to 1175. [2263] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 K132N protein mutation comprises one or more of the SEQ ID NOs: 1166 to 1175, SEQ ID NOs: 53250 to 53581, and SEQ ID NOs: 61169 to 61178. In some embodiments, any one of the peptides in the TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1166 to 1175, SEQ ID NOs: 53250 to 53581, or SEQ ID NOs: 61169 to 61178. [2264] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 K132N protein mutation comprises two or more of the SEQ ID NOs: 1166 to 1175. In some embodiments, any one of the peptides in the TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1166 to 1175. [2265] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 K132N protein mutation comprises two or more of the SEQ ID NOs: 1166 to 1175, SEQ ID NOs: 53250 to 53581, and SEQ ID NOs: 61169 to 61178. In some embodiments, any one of the peptides in the TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1166 to 1175, SEQ ID NOs: 53250 to 53581, or SEQ ID NOs: 61169 to 61178. [2266] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 P151S protein mutation comprises one or more of the SEQ ID NOs: 1176 to 1185. In some embodiments, any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1176 to 1185. [2267] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 P151S protein mutation comprises one or more of the SEQ ID NOs: 1176 to 1185, SEQ ID NOs: 53582 to 53605, and SEQ ID NOs: 61179 to 61188. In some embodiments, any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 457 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 identical to SEQ ID NOs: 1176 to 1185, SEQ ID NOs: 53582 to 53605, or SEQ ID NOs: 61179 to 61188. [2268] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 P151S protein mutation comprises two or more of the SEQ ID NOs: 1176 to 1185. In some embodiments, any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1176 to 1185. [2269] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 P151S protein mutation comprises two or more of the SEQ ID NOs: 1176 to 1185, SEQ ID NOs: 53582 to 53605, and SEQ ID NOs: 61179 to 61188. In some embodiments, any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1176 to 1185, SEQ ID NOs: 53582 to 53605, or SEQ ID NOs: 61179 to 61188. [2270] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R213L protein mutation comprises one or more of the SEQ ID NOs: 1186 to 1195. In some embodiments, any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1186 to 1195. [2271] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R213L protein mutation comprises one or more of the SEQ ID NOs: 1186 to 1195, SEQ ID NOs: 53606 to 56079, and SEQ ID NOs: 61189 to 61198. In some embodiments, any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1186 to 1195, SEQ ID NOs: 53606 to 56079, or SEQ ID NOs: 61189 to 61198. [2272] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R213L protein mutation comprises two or more of the SEQ ID NOs: 1186 to 1195. In some embodiments, any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1186 to 1195. - 458 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2273] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R213L protein mutation comprises two or more of the SEQ ID NOs: 1186 to 1195, SEQ ID NOs: 53606 to 56079, and SEQ ID NOs: 61189 to 61198. In some embodiments, any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1186 to 1195, SEQ ID NOs: 53606 to 56079, or SEQ ID NOs: 61189 to 61198. [2274] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R249M protein mutation comprises one or more of the SEQ ID NOs: 1196 to 1205. In some embodiments, any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1196 to 1205. [2275] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R249M protein mutation comprises one or more of the SEQ ID NOs: 1196 to 1205, SEQ ID NOs: 56080 to 56218, and SEQ ID NOs: 61199 to 61208. In some embodiments, any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1196 to 1205, SEQ ID NOs: 56080 to 56218, or SEQ ID NOs: 61199 to 61208. [2276] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R249M protein mutation comprises two or more of the SEQ ID NOs: 1196 to 1205. In some embodiments, any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1196 to 1205. [2277] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R249M protein mutation comprises two or more of the SEQ ID NOs: 1196 to 1205, SEQ ID NOs: 56080 to 56218, and SEQ ID NOs: 61199 to 61208. In some embodiments, any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1196 to 1205, SEQ ID NOs: 56080 to 56218, or SEQ ID NOs: 61199 to 61208. - 459 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2278] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R249S protein mutation comprises one or more of the SEQ ID NOs: 1206 to 1215. In some embodiments, any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1206 to 1215. [2279] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R249S protein mutation comprises one or more of the SEQ ID NOs: 1206 to 1215, SEQ ID NOs: 56219 to 56353, and SEQ ID NOs: 61209 to 61218. In some embodiments, any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1206 to 1215, SEQ ID NOs: 56219 to 56353, or SEQ ID NOs: 61209 to 61218. [2280] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R249S protein mutation comprises two or more of the SEQ ID NOs: 1206 to 1215. In some embodiments, any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1206 to 1215. [2281] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R249S protein mutation comprises two or more of the SEQ ID NOs: 1206 to 1215, SEQ ID NOs: 56219 to 56353, and SEQ ID NOs: 61209 to 61218. In some embodiments, any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1206 to 1215, SEQ ID NOs: 56219 to 56353, or SEQ ID NOs: 61209 to 61218. [2282] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R273L protein mutation comprises one or more of the SEQ ID NOs: 1216 to 1225. In some embodiments, any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1216 to 1225. [2283] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R273L protein mutation comprises one or more of the SEQ ID NOs: - 460 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 1216 to 1225, SEQ ID NOs: 56354 to 57451, and SEQ ID NOs: 61219 to 61228. In some embodiments, any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1216 to 1225, SEQ ID NOs: 56354 to 57451, or SEQ ID NOs: 61219 to 61228. [2284] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R273L protein mutation comprises two or more of the SEQ ID NOs: 1216 to 1225. In some embodiments, any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1216 to 1225. [2285] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 R273L protein mutation comprises two or more of the SEQ ID NOs: 1216 to 1225, SEQ ID NOs: 56354 to 57451, and SEQ ID NOs: 61219 to 61228. In some embodiments, any one of the peptides in the TP53 R273L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1216 to 1225, SEQ ID NOs: 56354 to 57451, or SEQ ID NOs: 61219 to 61228. [2286] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 S127Y protein mutation comprises one or more of the SEQ ID NOs: 1226 to 1235. In some embodiments, any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1226 to 1235. [2287] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 S127Y protein mutation comprises one or more of the SEQ ID NOs: 1226 to 1235, SEQ ID NOs: 57452 to 57791, and SEQ ID NOs: 61229 to 61238. In some embodiments, any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1226 to 1235, SEQ ID NOs: 57452 to 57791, or SEQ ID NOs: 61229 to 61238. [2288] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 S127Y protein mutation comprises two or more of the SEQ ID NOs: - 461 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 1226 to 1235. In some embodiments, any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1226 to 1235. [2289] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 S127Y protein mutation comprises two or more of the SEQ ID NOs: 1226 to 1235, SEQ ID NOs: 57452 to 57791, and SEQ ID NOs: 61229 to 61238. In some embodiments, any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1226 to 1235, SEQ ID NOs: 57452 to 57791, or SEQ ID NOs: 61229 to 61238. [2290] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 S241F protein mutation comprises one or more of the SEQ ID NOs: 1236 to 1245. In some embodiments, any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1236 to 1245. [2291] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 S241F protein mutation comprises one or more of the SEQ ID NOs: 1236 to 1245, SEQ ID NOs: 57792 to 57958, and SEQ ID NOs: 61239 to 61248. In some embodiments, any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1236 to 1245, SEQ ID NOs: 57792 to 57958, or SEQ ID NOs: 61239 to 61248. [2292] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 S241F protein mutation comprises two or more of the SEQ ID NOs: 1236 to 1245. In some embodiments, any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1236 to 1245. [2293] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 S241F protein mutation comprises two or more of the SEQ ID NOs: 1236 to 1245, SEQ ID NOs: 57792 to 57958, and SEQ ID NOs: 61239 to 61248. In some embodiments, any one of the peptides in the TP53 S241F composition comprise an amino acid - 462 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1236 to 1245, SEQ ID NOs: 57792 to 57958, or SEQ ID NOs: 61239 to 61248. [2294] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 V157F protein mutation comprises one or more of the SEQ ID NOs: 1246 to 1255. In some embodiments, any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1246 to 1255. [2295] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 V157F protein mutation comprises one or more of the SEQ ID NOs: 1246 to 1255, SEQ ID NOs: 57959 to 58049, and SEQ ID NOs: 61249 to 61258. In some embodiments, any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1246 to 1255, SEQ ID NOs: 57959 to 58049, or SEQ ID NOs: 61249 to 61258. [2296] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 V157F protein mutation comprises two or more of the SEQ ID NOs: 1246 to 1255. In some embodiments, any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1246 to 1255. [2297] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 V157F protein mutation comprises two or more of the SEQ ID NOs: 1246 to 1255, SEQ ID NOs: 57959 to 58049, and SEQ ID NOs: 61249 to 61258. In some embodiments, any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1246 to 1255, SEQ ID NOs: 57959 to 58049, or SEQ ID NOs: 61249 to 61258. [2298] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 V272M protein mutation comprises one or more of the SEQ ID NOs: 1256 to 1259. In some embodiments, any one of the peptides in the TP53 V272M composition - 463 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1256 to 1259. [2299] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 V272M protein mutation comprises one or more of the SEQ ID NOs: 1256 to 1259, SEQ ID NO: 58050, and SEQ ID NOs: 61259 to 61262. In some embodiments, any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1256 to 1259, SEQ ID NO: 58050, or SEQ ID NOs: 61259 to 61262. [2300] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 V272M protein mutation comprises two or more of the SEQ ID NOs: 1256 to 1259. In some embodiments, any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1256 to 1259. [2301] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 V272M protein mutation comprises two or more of the SEQ ID NOs: 1256 to 1259, SEQ ID NO: 58050, and SEQ ID NOs: 61259 to 61262. In some embodiments, any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1256 to 1259, SEQ ID NO: 58050, or SEQ ID NOs: 61259 to 61262. [2302] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 Y163C protein mutation comprises one or more of the SEQ ID NOs: 1260 to 1269. In some embodiments, any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1260 to 1269. [2303] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 Y163C protein mutation comprises one or more of the SEQ ID NOs: 1260 to 1269, SEQ ID NOs: 58051 to 60804, and SEQ ID NOs: 61263 to 61271. In some embodiments, any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1260 to 1269, SEQ ID NOs: 58051 to 60804, or SEQ ID NOs: 61263 to 61271. - 464 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [2304] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 Y163C protein mutation comprises two or more of the SEQ ID NOs: 1260 to 1269. In some embodiments, any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1260 to 1269. [2305] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 Y163C protein mutation comprises two or more of the SEQ ID NOs: 1260 to 1269, SEQ ID NOs: 58051 to 60804, and SEQ ID NOs: 61263 to 61271. In some embodiments, any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1260 to 1269, SEQ ID NOs: 58051 to 60804, or SEQ ID NOs: 61263 to 61271. [2306] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 Y205C protein mutation comprises one or more of the SEQ ID NOs: 1270 to 1279. In some embodiments, any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1270 to 1279. [2307] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 Y205C protein mutation comprises one or more of the SEQ ID NOs: 1270 to 1279, SEQ ID NOs: 60805 to 60853, and SEQ ID NOs: 61272 to 61281. In some embodiments, any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1270 to 1279, SEQ ID NOs: 60805 to 60853, or SEQ ID NOs: 61272 to 61281. [2308] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 Y205C protein mutation comprises two or more of the SEQ ID NOs: 1270 to 1279. In some embodiments, any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1270 to 1279. [2309] In some embodiments, the amino acid sequence for a MHC class II peptide composition for the TP53 Y205C protein mutation comprises two or more of the SEQ ID NOs: - 465 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 1270 to 1279, SEQ ID NOs: 60805 to 60853, and SEQ ID NOs: 61272 to 61281. In some embodiments, any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1270 to 1279, SEQ ID NOs: 60805 to 60853, or SEQ ID NOs: 61272 to 61281. [2310] Table 2 summarizes MHC class II peptide sequences described herein including the respective SEQ ID NO, amino acid sequence corresponding to the SEQ ID NO, the amino acid sequence corresponding to the peptide's binding core, the protein target (with specific mutation), the seed amino acid sequence (i.e., the amino acid sequence of the wild-type KRAS fragment), the seed amino acid sequence of the binding core, and the amino acid substitution (if any) for heteroclitic peptides at positions 1, 4, 6, and 9. Table 2 includes peptide sequences comprising SEQ ID NOs: 835 to 1279. SEQ ID NOs: 835 to 1279 (Table 2) encode for recombinant peptides. In some embodiments, any combination of peptides listed in Table 2 (SEQ ID NOs: 835 to 1279) may be used to create a single target (individual) or combined peptide composition having between about 2 and about 40 peptides. In some embodiments, any one of the peptides (peptides 835 to 1279; SEQ ID NOs: 835 to 1279) in the combined composition comprises an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to any of SEQ ID NOs: 835 to 1279. [2311] Additional amino acid sequences of MHC class II composition peptides are provided in Sequence Listings (SEQ ID NOs: 36797 to 61281). In some embodiments, any combination of MHC class II peptides disclosed herein (SEQ ID NOs: 835 to 1279 and SEQ ID NOs: 36797 to 61281) may be used to create a combined peptide composition having between about 2 and about 40 peptides. In some embodiments, any one of the peptides (SEQ ID NOs: 835 to 1279 and SEQ ID NOs: 36797 to 61281) in the combined composition comprises or contains an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to any of SEQ ID NOs: 835 to 1279 or SEQ ID NOs: 36797 to 61281. [2312] In some embodiments, the composition comprising the MHC class II peptides disclosed herein is an immunogenic composition. In some embodiments, the composition is a vaccine. [2313] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for mutation in the BRAF protein having between about 2 and about 40 peptides. In some - 466 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 embodiments, any one of the peptides in the composition for mutation in the BRAF protein comprises one or more of the SEQ ID NOs: 1 to 16, SEQ ID NO: 795, SEQ ID NOs: 835 to 844, SEQ ID NOs: 1280 to 2625, SEQ ID NOs: 36797 to 36907, and SEQ ID NOs: 60854 to 60863. In some embodiments, any one of the peptides in the BRAF composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16, SEQ ID NO: 795, SEQ ID NOs: 835 to 844, SEQ ID NOs: 1280 to 2625, SEQ ID NOs: 36797 to 36907, or SEQ ID NOs: 60854 to 60863. [2314] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for mutation in the CTNNB1 protein having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for mutation in the CTNNB1 protein comprises one or more of the SEQ ID NOs: 17 to 184, SEQ ID NOs: 796 to 801, SEQ ID NOs: 845 to 935, SEQ ID NOs: 2626 to 8516, SEQ ID NOs: 36908 to 40038, and SEQ ID NOs: 60864 to 60946. In some embodiments, any one of the peptides in the CTNNB1 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 184, SEQ ID NOs: 796 to 801, SEQ ID NOs: 845 to 935, SEQ ID NOs: 2626 to 8516, SEQ ID NOs: 36908 to 40038, or SEQ ID NOs: 60864 to 60946. [2315] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for mutation in the KRAS protein having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for mutation in the KRAS protein comprises one or more of the SEQ ID NOs: 185 to 222, SEQ ID NOs: 802 to 803, SEQ ID NOs: 936 to 965, SEQ ID NOs: 8517 to 10266, SEQ ID NOs: 40039 to 43494, and SEQ ID NOs: 60947 to 60976. In some embodiments, any one of the peptides in the KRAS composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 222, SEQ ID NOs: 802 to 803, SEQ ID NOs: 936 to 965, SEQ ID NOs: 8517 to 10266, SEQ ID NOs: 40039 to 43494, or SEQ ID NOs: 60947 to 60976. [2316] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for mutation in the PIK3CA protein having between about 2 and about 40 peptides. In some - 467 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 embodiments, any one of the peptides in the composition for mutation in the PIK3CA protein comprises one or more of the SEQ ID NOs: 223 to 386, SEQ ID NOs: 804 to 813, SEQ ID NOs: 966 to 1065, SEQ ID NOs: 10267 to 15528, SEQ ID NOs: 43495 to 49560, and SEQ ID NOs: 60977 to 61069. In some embodiments, any one of the peptides in the PIK3CA composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 386, SEQ ID NOs: 804 to 813, SEQ ID NOs: 966 to 1065, SEQ ID NOs: 10267 to 15528, SEQ ID NOs: 43495 to 49560, or SEQ ID NOs: 60977 to 61069. [2317] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for mutation in the TP53 protein having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for mutation in the TP53 protein comprises one or more of the SEQ ID NOs: 387 to 794, SEQ ID NOs: 814 to 834, SEQ ID NOs: 1066 to 1279, SEQ ID NOs: 15529 to 36796, SEQ ID NOs: 49561 to 60853, and SEQ ID NOs: 61070 to 61281. In some embodiments, any one of the peptides in the TP53 composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 794, SEQ ID NOs: 814 to 834, SEQ ID NOs: 1066 to 1279, SEQ ID NOs: 15529 to 36796, SEQ ID NOs: 49561 to 60853, or SEQ ID NOs: 61070 to 61281. [2318] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the BRAF G466V protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the BRAF G466V protein mutation comprises one or more of the SEQ ID NOs: 1 to 16, SEQ ID NO: 795, SEQ ID NOs: 835 to 844, SEQ ID NOs: 1280 to 2625, SEQ ID NOs: 36797 to 36907, and SEQ ID NOs: 60854 to 60863. In some embodiments, any one of the peptides in the BRAF G466V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 1 to 16, SEQ ID NO: 795, SEQ ID NOs: 835 to 844, SEQ ID NOs: 1280 to 2625, SEQ ID NOs: 36797 to 36907, or SEQ ID NOs: 60854 to 60863. [2319] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the CTNNB1 D32G protein mutation having between about 2 and about 40 peptides. In some - 468 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 embodiments, any one of the peptides in the composition for the CTNNB1 D32G protein mutation comprises one or more of the SEQ ID NOs: 17 to 36, SEQ ID NOs: 845 to 854, SEQ ID NOs: 2626 to 3063, SEQ ID NOs: 36908 to 37076, and SEQ ID NOs: 60864 to 60872. In some embodiments, any one of the peptides in the CTNNB1 D32G composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 17 to 36, SEQ ID NOs: 845 to 854, SEQ ID NOs: 2626 to 3063, SEQ ID NOs: 36908 to 37076, or SEQ ID NOs: 60864 to 60872. [2320] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the CTNNB1 G34E protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the CTNNB1 G34E protein mutation comprises one or more of the SEQ ID NOs: 37 to 52, SEQ ID NOs: 855 to 864, SEQ ID NOs: 3064 to 3582, SEQ ID NOs: 37077 to 37185, and SEQ ID NOs: 60873 to 60882. In some embodiments, any one of the peptides in the CTNNB1 G34E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 37 to 52, SEQ ID NOs: 855 to 864, SEQ ID NOs: 3064 to 3582, SEQ ID NOs: 37077 to 37185, or SEQ ID NOs: 60873 to 60882. [2321] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the CTNNB1 S33C protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the CTNNB1 S33C protein mutation comprises one or more of the SEQ ID NOs: 53 to 67, SEQ ID NO: 865, SEQ ID NOs: 3583 to 3914, SEQ ID NOs: 37186 to 37234, and SEQ ID NO: 60883. In some embodiments, any one of the peptides in the CTNNB1 S33C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 53 to 67, SEQ ID NO: 865, SEQ ID NOs: 3583 to 3914, SEQ ID NOs: 37186 to 37234, or SEQ ID NO: 60883. [2322] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the CTNNB1 S33F protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the CTNNB1 S33F protein mutation comprises one or more of the SEQ ID NOs: 68 to 86, SEQ ID NOs: 866 to 875, SEQ - 469 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 ID NOs: 3915 to 4542, SEQ ID NOs: 37235 to 37344, and SEQ ID NOs: 60884 to 60891. In some embodiments, any one of the peptides in the CTNNB1 S33F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 68 to 86, SEQ ID NOs: 866 to 875, SEQ ID NOs: 3915 to 4542, SEQ ID NOs: 37235 to 37344, or SEQ ID NOs: 60884 to 60891. [2323] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the CTNNB1 S37C protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the CTNNB1 S37C protein mutation comprises one or more of the SEQ ID NOs: 87 to 102, SEQ ID NO: 796, SEQ ID NOs: 876 to 885, SEQ ID NOs: 4543 to 5000, SEQ ID NOs: 37345 to 37456, and SEQ ID NOs: 60892 to 60899. In some embodiments, any one of the peptides in the CTNNB1 S37C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 87 to 102, SEQ ID NO: 796, SEQ ID NOs: 876 to 885, SEQ ID NOs: 4543 to 5000, SEQ ID NOs: 37345 to 37456, or SEQ ID NOs: 60892 to 60899. [2324] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the CTNNB1 S37F protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the CTNNB1 S37F protein mutation comprises one or more of the SEQ ID NOs: 103 to 119, SEQ ID NOs: 886 to 895, SEQ ID NOs: 5001 to 5916, SEQ ID NOs: 37457 to 38596, and SEQ ID NOs: 60900 to 60908. In some embodiments, any one of the peptides in the CTNNB1 S37F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 103 to 119, SEQ ID NOs: 886 to 895, SEQ ID NOs: 5001 to 5916, SEQ ID NOs: 37457 to 38596, or SEQ ID NOs: 60900 to 60908. [2325] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the CTNNB1 S45F protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the CTNNB1 S45F protein mutation comprises one or more of the SEQ ID NOs: 120 to 134, SEQ ID NO: 797, SEQ ID NOs: 896 to 905, SEQ ID NOs: 5917 to 6394, SEQ ID NOs: 38597 to 38651, and SEQ ID NOs: - 470 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 60909 to 60917. In some embodiments, any one of the peptides in the CTNNB1 S45F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 120 to 134, SEQ ID NO: 797, SEQ ID NOs: 896 to 905, SEQ ID NOs: 5917 to 6394, SEQ ID NOs: 38597 to 38651, or SEQ ID NOs: 60909 to 60917. [2326] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the CTNNB1 S45P protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the CTNNB1 S45P protein mutation comprises one or more of the SEQ ID NOs: 135 to 150, SEQ ID NO: 798, SEQ ID NOs: 906 to 915, SEQ ID NOs: 6395 to 7051, SEQ ID NOs: 38652 to 38686, and SEQ ID NOs: 60918 to 60927. In some embodiments, any one of the peptides in the CTNNB1 S45P composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 135 to 150, SEQ ID NO: 798, SEQ ID NOs: 906 to 915, SEQ ID NOs: 6395 to 7051, SEQ ID NOs: 38652 to 38686, or SEQ ID NOs: 60918 to 60927. [2327] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the CTNNB1 T41A protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the CTNNB1 T41A protein mutation comprises one or more of the SEQ ID NOs: 151 to 167, SEQ ID NOs: 799 to 800, SEQ ID NOs: 916 to 925, SEQ ID NOs: 7052 to 7846, SEQ ID NOs: 38687 to 38944, and SEQ ID NOs: 60928 to 60936. In some embodiments, any one of the peptides in the CTNNB1 T41A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 151 to 167, SEQ ID NOs: 799 to 800, SEQ ID NOs: 916 to 925, SEQ ID NOs: 7052 to 7846, SEQ ID NOs: 38687 to 38944, or SEQ ID NOs: 60928 to 60936. [2328] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the CTNNB1 T41I protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the CTNNB1 T41I protein mutation comprises one or more of the SEQ ID NOs: 168 to 184, SEQ ID NO: 801, SEQ ID - 471 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 NOs: 926 to 935, SEQ ID NOs: 7847 to 8516, SEQ ID NOs: 38945 to 40038, and SEQ ID NOs: 60937 to 60946. In some embodiments, any one of the peptides in the CTNNB1 T41I composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 168 to 184, SEQ ID NO: 801, SEQ ID NOs: 926 to 935, SEQ ID NOs: 7847 to 8516, SEQ ID NOs: 38945 to 40038, or SEQ ID NOs: 60937 to 60946. [2329] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the KRAS A146T protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the KRAS A146T protein mutation comprises one or more of the SEQ ID NOs: 185 to 193, SEQ ID NO: 802, SEQ ID NOs: 936 to 945, SEQ ID NOs: 8517 to 8904, SEQ ID NOs: 40039 to 40142, and SEQ ID NOs: 60947 to 60956. In some embodiments, any one of the peptides in the KRAS A146T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 185 to 193, SEQ ID NO: 802, SEQ ID NOs: 936 to 945, SEQ ID NOs: 8517 to 8904, SEQ ID NOs: 40039 to 40142, or SEQ ID NOs: 60947 to 60956. [2330] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the KRAS A146V protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the KRAS A146V protein mutation comprises one or more of the SEQ ID NOs: 194 to 202, SEQ ID NO: 803, SEQ ID NOs: 946 to 955, SEQ ID NOs: 8905 to 9308, SEQ ID NOs: 40143 to 43468, and SEQ ID NOs: 60957 to 60966. In some embodiments, any one of the peptides in the KRAS A146V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 194 to 202, SEQ ID NO: 803, SEQ ID NOs: 946 to 955, SEQ ID NOs: 8905 to 9308, SEQ ID NOs: 40143 to 43468, or SEQ ID NOs: 60957 to 60966. [2331] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the KRAS Q61H protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the KRAS Q61H protein mutation - 472 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 comprises one or more of the SEQ ID NOs: 203 to 222, SEQ ID NOs: 956 to 965, SEQ ID NOs: 9309 to 10266, SEQ ID NOs: 43469 to 43494, and SEQ ID NOs: 60967 to 60976. In some embodiments, any one of the peptides in the KRAS Q61H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 203 to 222, SEQ ID NOs: 956 to 965, SEQ ID NOs: 9309 to 10266, SEQ ID NOs: 43469 to 43494, or SEQ ID NOs: 60967 to 60976. [2332] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the PIK3CA C420R protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the PIK3CA C420R protein mutation comprises one or more of the SEQ ID NOs: 223 to 239, SEQ ID NOs: 804 to 805, SEQ ID NOs: 966 to 975, SEQ ID NOs: 10267 to 10781, SEQ ID NOs: 43495 to 43802, and SEQ ID NOs: 60977 to 60985. In some embodiments, any one of the peptides in the PIK3CA C420R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 223 to 239, SEQ ID NOs: 804 to 805, SEQ ID NOs: 966 to 975, SEQ ID NOs: 10267 to 10781, SEQ ID NOs: 43495 to 43802, or SEQ ID NOs: 60977 to 60985. [2333] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the PIK3CA E453K protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the PIK3CA E453K protein mutation comprises one or more of the SEQ ID NOs: 240 to 255, SEQ ID NOs: 806 to 807, SEQ ID NOs: 976 to 985, SEQ ID NOs: 10782 to 11260, SEQ ID NOs: 43803 to 43939, and SEQ ID NOs: 60986 to 60995. In some embodiments, any one of the peptides in the PIK3CA E453K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 240 to 255, SEQ ID NOs: 806 to 807, SEQ ID NOs: 976 to 985, SEQ ID NOs: 10782 to 11260, SEQ ID NOs: 43803 to 43939, or SEQ ID NOs: 60986 to 60995. [2334] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the PIK3CA E545A protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the PIK3CA E545A protein - 473 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 mutation comprises one or more of the SEQ ID NOs: 256 to 271, SEQ ID NO: 808, SEQ ID NOs: 986 to 995, SEQ ID NOs: 11261 to 11604, SEQ ID NOs: 43940 to 43970, and SEQ ID NOs: 60996 to 61004. In some embodiments, any one of the peptides in the PIK3CA E545A composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 256 to 271, SEQ ID NO: 808, SEQ ID NOs: 986 to 995, SEQ ID NOs: 11261 to 11604, SEQ ID NOs: 43940 to 43970, or SEQ ID NOs: 60996 to 61004. [2335] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the PIK3CA E726K protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the PIK3CA E726K protein mutation comprises one or more of the SEQ ID NOs: 272 to 290, SEQ ID NO: 809, SEQ ID NOs: 996 to 1005, SEQ ID NOs: 11605 to 12160, SEQ ID NOs: 43971 to 47907, and SEQ ID NOs: 61005 to 61014. In some embodiments, any one of the peptides in the PIK3CA E726K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 272 to 290, SEQ ID NO: 809, SEQ ID NOs: 996 to 1005, SEQ ID NOs: 11605 to 12160, SEQ ID NOs: 43971 to 47907, or SEQ ID NOs: 61005 to 61014. [2336] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the PIK3CA G118D protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the PIK3CA G118D protein mutation comprises one or more of the SEQ ID NOs: 291 to 307, SEQ ID NOs: 1006 to 1015, SEQ ID NOs: 12161 to 12944, SEQ ID NOs: 47908 to 48313, and SEQ ID NOs: 61015 to 61024. In some embodiments, any one of the peptides in the PIK3CA G118D composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 291 to 307, SEQ ID NOs: 1006 to 1015, SEQ ID NOs: 12161 to 12944, SEQ ID NOs: 47908 to 48313, or SEQ ID NOs: 61015 to 61024. [2337] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the PIK3CA H1047L protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the PIK3CA H1047L protein - 474 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 mutation comprises one or more of the SEQ ID NOs: 308 to 325, SEQ ID NOs: 1016 to 1025, SEQ ID NOs: 12945 to 13568, SEQ ID NOs: 48314 to 49032, and SEQ ID NOs: 61025 to 61034. In some embodiments, any one of the peptides in the PIK3CA H1047L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 308 to 325, SEQ ID NOs: 1016 to 1025, SEQ ID NOs: 12945 to 13568, SEQ ID NOs: 48314 to 49032, or SEQ ID NOs: 61025 to 61034. [2338] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the PIK3CA N345K protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the PIK3CA N345K protein mutation comprises one or more of the SEQ ID NOs: 326 to 339, SEQ ID NOs: 810 to 811, SEQ ID NOs: 1026 to 1035, SEQ ID NOs: 13569 to 13997, SEQ ID NOs: 49033 to 49385, and SEQ ID NOs: 61035 to 61044. In some embodiments, any one of the peptides in the PIK3CA N345K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 326 to 339, SEQ ID NOs: 810 to 811, SEQ ID NOs: 1026 to 1035, SEQ ID NOs: 13569 to 13997, SEQ ID NOs: 49033 to 49385, or SEQ ID NOs: 61035 to 61044. [2339] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the PIK3CA Q546K protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the PIK3CA Q546K protein mutation comprises one or more of the SEQ ID NOs: 340 to 358, SEQ ID NO: 812, SEQ ID NOs: 1036 to 1045, SEQ ID NOs: 13998 to 14491, SEQ ID NOs: 49386 to 49421, and SEQ ID NOs: 61045 to 61051. In some embodiments, any one of the peptides in the PIK3CA Q546K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 340 to 358, SEQ ID NO: 812, SEQ ID NOs: 1036 to 1045, SEQ ID NOs: 13998 to 14491, SEQ ID NOs: 49386 to 49421, or SEQ ID NOs: 61045 to 61051. [2340] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the PIK3CA Q546R protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the PIK3CA Q546R protein - 475 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 mutation comprises one or more of the SEQ ID NOs: 359 to 376, SEQ ID NO: 813, SEQ ID NOs: 1046 to 1055, SEQ ID NOs: 14492 to 15002, SEQ ID NOs: 49422 to 49471, and SEQ ID NOs: 61052 to 61059. In some embodiments, any one of the peptides in the PIK3CA Q546R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 359 to 376, SEQ ID NO: 813, SEQ ID NOs: 1046 to 1055, SEQ ID NOs: 14492 to 15002, SEQ ID NOs: 49422 to 49471, or SEQ ID NOs: 61052 to 61059. [2341] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the PIK3CA R108H protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the PIK3CA R108H protein mutation comprises one or more of the SEQ ID NOs: 377 to 386, SEQ ID NOs: 1056 to 1065, SEQ ID NOs: 15003 to 15528, SEQ ID NOs: 49472 to 49560, and SEQ ID NOs: 61060 to 61069. In some embodiments, any one of the peptides in the PIK3CA R108H composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 377 to 386, SEQ ID NOs: 1056 to 1065, SEQ ID NOs: 15003 to 15528, SEQ ID NOs: 49472 to 49560, or SEQ ID NOs: 61060 to 61069. [2342] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 C176F protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 C176F protein mutation comprises one or more of the SEQ ID NOs: 387 to 403, SEQ ID NOs: 814 to 815, SEQ ID NOs: 1066 to 1075, SEQ ID NOs: 15529 to 16093, SEQ ID NOs: 49561 to 49621, and SEQ ID NOs: 61070 to 61079. In some embodiments, any one of the peptides in the TP53 C176F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 387 to 403, SEQ ID NOs: 814 to 815, SEQ ID NOs: 1066 to 1075, SEQ ID NOs: 15529 to 16093, SEQ ID NOs: 49561 to 49621, or SEQ ID NOs: 61070 to 61079. [2343] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 C176Y protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 C176Y protein mutation - 476 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 comprises one or more of the SEQ ID NOs: 404 to 420, SEQ ID NO: 816, SEQ ID NOs: 1076 to 1085, SEQ ID NOs: 16094 to 16634, SEQ ID NOs: 49622 to 49675, and SEQ ID NOs: 61080 to 61089. In some embodiments, any one of the peptides in the TP53 C176Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 404 to 420, SEQ ID NO: 816, SEQ ID NOs: 1076 to 1085, SEQ ID NOs: 16094 to 16634, SEQ ID NOs: 49622 to 49675, or SEQ ID NOs: 61080 to 61089. [2344] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 C238Y protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 C238Y protein mutation comprises one or more of the SEQ ID NOs: 421 to 440, SEQ ID NOs: 1086 to 1095, SEQ ID NOs: 16635 to 17413, SEQ ID NOs: 49676 to 50263, and SEQ ID NOs: 61090 to 61099. In some embodiments, any one of the peptides in the TP53 C238Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 421 to 440, SEQ ID NOs: 1086 to 1095, SEQ ID NOs: 16635 to 17413, SEQ ID NOs: 49676 to 50263, or SEQ ID NOs: 61090 to 61099. [2345] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 C275Y protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 C275Y protein mutation comprises one or more of the SEQ ID NOs: 441 to 457, SEQ ID NOs: 1096 to 1105, SEQ ID NOs: 17414 to 18100, SEQ ID NOs: 50264 to 50368, and SEQ ID NOs: 61100 to 61109. In some embodiments, any one of the peptides in the TP53 C275Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 441 to 457, SEQ ID NOs: 1096 to 1105, SEQ ID NOs: 17414 to 18100, SEQ ID NOs: 50264 to 50368, or SEQ ID NOs: 61100 to 61109. [2346] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 E285K protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 E285K protein mutation comprises one or more of the SEQ ID NOs: 458 to 473, SEQ ID NOs: 817 to 818, and SEQ ID - 477 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 NOs: 18101 to 18739. In some embodiments, any one of the peptides in the TP53 E285K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 458 to 473, SEQ ID NOs: 817 to 818, or SEQ ID NOs: 18101 to 18739. [2347] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 G245S protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 G245S protein mutation comprises one or more of the SEQ ID NOs: 474 to 492, SEQ ID NOs: 1106 to 1115, SEQ ID NOs: 18740 to 19567, SEQ ID NOs: 50369 to 50579, and SEQ ID NOs: 61110 to 61119. In some embodiments, any one of the peptides in the TP53 G245S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 474 to 492, SEQ ID NOs: 1106 to 1115, SEQ ID NOs: 18740 to 19567, SEQ ID NOs: 50369 to 50579, or SEQ ID NOs: 61110 to 61119. [2348] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 G245V protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 G245V protein mutation comprises one or more of the SEQ ID NOs: 493 to 511, SEQ ID NOs: 1116 to 1125, SEQ ID NOs: 19568 to 20400, SEQ ID NOs: 50580 to 50709, and SEQ ID NOs: 61120 to 61129. In some embodiments, any one of the peptides in the TP53 G245V composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 493 to 511, SEQ ID NOs: 1116 to 1125, SEQ ID NOs: 19568 to 20400, SEQ ID NOs: 50580 to 50709, or SEQ ID NOs: 61120 to 61129. [2349] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 H179Y protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 H179Y protein mutation comprises one or more of the SEQ ID NOs: 512 to 529, SEQ ID NOs: 819 to 820, SEQ ID NOs: 1126 to 1135, SEQ ID NOs: 20401 to 20880, SEQ ID NOs: 50710 to 50755, and SEQ ID NOs: 61130 to 61139. In some embodiments, any one of the peptides in the TP53 H179Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, - 478 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 512 to 529, SEQ ID NOs: 819 to 820, SEQ ID NOs: 1126 to 1135, SEQ ID NOs: 20401 to 20880, SEQ ID NOs: 50710 to 50755, or SEQ ID NOs: 61130 to 61139. [2350] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 H193R protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 H193R protein mutation comprises one or more of the SEQ ID NOs: 530 to 546, SEQ ID NOs: 1136 to 1145, SEQ ID NOs: 20881 to 21921, SEQ ID NOs: 50756 to 51569, and SEQ ID NOs: 61140 to 61149. In some embodiments, any one of the peptides in the TP53 H193R composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 530 to 546, SEQ ID NOs: 1136 to 1145, SEQ ID NOs: 20881 to 21921, SEQ ID NOs: 50756 to 51569, or SEQ ID NOs: 61140 to 61149. [2351] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 I195T protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 I195T protein mutation comprises one or more of the SEQ ID NOs: 547 to 563, SEQ ID NO: 821, SEQ ID NOs: 1146 to 1155, SEQ ID NOs: 21922 to 22738, SEQ ID NOs: 51570 to 53061, and SEQ ID NOs: 61150 to 61159. In some embodiments, any one of the peptides in the TP53 I195T composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 547 to 563, SEQ ID NO: 821, SEQ ID NOs: 1146 to 1155, SEQ ID NOs: 21922 to 22738, SEQ ID NOs: 51570 to 53061, or SEQ ID NOs: 61150 to 61159. [2352] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 K132E protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 K132E protein mutation comprises one or more of the SEQ ID NOs: 564 to 582, SEQ ID NO: 822, SEQ ID NOs: 1156 to 1165, SEQ ID NOs: 22739 to 24317, SEQ ID NOs: 53062 to 53249, and SEQ ID NOs: 61160 to 61168. In some embodiments, any one of the peptides in the TP53 K132E composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 564 to 582, SEQ ID NO: 822, SEQ ID NOs: 1156 - 479 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 to 1165, SEQ ID NOs: 22739 to 24317, SEQ ID NOs: 53062 to 53249, or SEQ ID NOs: 61160 to 61168. [2353] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 K132N protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 K132N protein mutation comprises one or more of the SEQ ID NOs: 583 to 599, SEQ ID NOs: 823 to 824, SEQ ID NOs: 1166 to 1175, SEQ ID NOs: 24318 to 25729, SEQ ID NOs: 53250 to 53581, and SEQ ID NOs: 61169 to 61178. In some embodiments, any one of the peptides in the TP53 K132N composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 583 to 599, SEQ ID NOs: 823 to 824, SEQ ID NOs: 1166 to 1175, SEQ ID NOs: 24318 to 25729, SEQ ID NOs: 53250 to 53581, or SEQ ID NOs: 61169 to 61178. [2354] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 P151S protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 P151S protein mutation comprises one or more of the SEQ ID NOs: 600 to 614, SEQ ID NOs: 825 to 826, SEQ ID NOs: 1176 to 1185, SEQ ID NOs: 25730 to 26739, SEQ ID NOs: 53582 to 53605, and SEQ ID NOs: 61179 to 61188. In some embodiments, any one of the peptides in the TP53 P151S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 600 to 614, SEQ ID NOs: 825 to 826, SEQ ID NOs: 1176 to 1185, SEQ ID NOs: 25730 to 26739, SEQ ID NOs: 53582 to 53605, or SEQ ID NOs: 61179 to 61188. [2355] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 R213L protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 R213L protein mutation comprises one or more of the SEQ ID NOs: 615 to 631, SEQ ID NOs: 827 to 828, SEQ ID NOs: 1186 to 1195, SEQ ID NOs: 26740 to 27926, SEQ ID NOs: 53606 to 56079, and SEQ ID NOs: 61189 to 61198. In some embodiments, any one of the peptides in the TP53 R213L composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, - 480 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 96, 97, 98 or 99 % identical to SEQ ID NOs: 615 to 631, SEQ ID NOs: 827 to 828, SEQ ID NOs: 1186 to 1195, SEQ ID NOs: 26740 to 27926, SEQ ID NOs: 53606 to 56079, or SEQ ID NOs: 61189 to 61198. [2356] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 R249M protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 R249M protein mutation comprises one or more of the SEQ ID NOs: 632 to 648, SEQ ID NO: 829, SEQ ID NOs: 1196 to 1205, SEQ ID NOs: 27927 to 29616, SEQ ID NOs: 56080 to 56218, and SEQ ID NOs: 61199 to 61208. In some embodiments, any one of the peptides in the TP53 R249M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 632 to 648, SEQ ID NO: 829, SEQ ID NOs: 1196 to 1205, SEQ ID NOs: 27927 to 29616, SEQ ID NOs: 56080 to 56218, or SEQ ID NOs: 61199 to 61208. [2357] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 R249S protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 R249S protein mutation comprises one or more of the SEQ ID NOs: 649 to 665, SEQ ID NO: 830, SEQ ID NOs: 1206 to 1215, SEQ ID NOs: 29617 to 31034, SEQ ID NOs: 56219 to 56353, and SEQ ID NOs: 61209 to 61218. In some embodiments, any one of the peptides in the TP53 R249S composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 649 to 665, SEQ ID NO: 830, SEQ ID NOs: 1206 to 1215, SEQ ID NOs: 29617 to 31034, SEQ ID NOs: 56219 to 56353, or SEQ ID NOs: 61209 to 61218. [2358] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 R273L protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 R273L protein mutation comprises one or more of the SEQ ID NOs: 666 to 680, SEQ ID NO: 831, SEQ ID NOs: 1216 to 1225, SEQ ID NOs: 31035 to 31564, SEQ ID NOs: 56354 to 57451, and SEQ ID NOs: 61219 to 61228. In some embodiments, any one of the peptides in the TP53 R273L composition - 481 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 666 to 680, SEQ ID NO: 831, SEQ ID NOs: 1216 to 1225, SEQ ID NOs: 31035 to 31564, SEQ ID NOs: 56354 to 57451, or SEQ ID NOs: 61219 to 61228. [2359] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 R280K protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 R280K protein mutation comprises one or more of the SEQ ID NO: 681 and SEQ ID NOs: 31565 to 31615. In some embodiments, any one of the peptides in the TP53 R280K composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 681 or SEQ ID NOs: 31565 to 31615. [2360] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 S127Y protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 S127Y protein mutation comprises one or more of the SEQ ID NOs: 682 to 700, SEQ ID NO: 832, SEQ ID NOs: 1226 to 1235, SEQ ID NOs: 31616 to 32944, SEQ ID NOs: 57452 to 57791, and SEQ ID NOs: 61229 to 61238. In some embodiments, any one of the peptides in the TP53 S127Y composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 682 to 700, SEQ ID NO: 832, SEQ ID NOs: 1226 to 1235, SEQ ID NOs: 31616 to 32944, SEQ ID NOs: 57452 to 57791, or SEQ ID NOs: 61229 to 61238. [2361] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 S241F protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 S241F protein mutation comprises one or more of the SEQ ID NOs: 701 to 718, SEQ ID NOs: 1236 to 1245, SEQ ID NOs: 32945 to 33558, SEQ ID NOs: 57792 to 57958, and SEQ ID NOs: 61239 to 61248. In some embodiments, any one of the peptides in the TP53 S241F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % - 482 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 identical to SEQ ID NOs: 701 to 718, SEQ ID NOs: 1236 to 1245, SEQ ID NOs: 32945 to 33558, SEQ ID NOs: 57792 to 57958, or SEQ ID NOs: 61239 to 61248. [2362] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 V157F protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 V157F protein mutation comprises one or more of the SEQ ID NOs: 719 to 738, SEQ ID NOs: 1246 to 1255, SEQ ID NOs: 33559 to 34612, SEQ ID NOs: 57959 to 58049, and SEQ ID NOs: 61249 to 61258. In some embodiments, any one of the peptides in the TP53 V157F composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 719 to 738, SEQ ID NOs: 1246 to 1255, SEQ ID NOs: 33559 to 34612, SEQ ID NOs: 57959 to 58049, or SEQ ID NOs: 61249 to 61258. [2363] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 V272M protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 V272M protein mutation comprises one or more of the SEQ ID NOs: 739 to 755, SEQ ID NOs: 1256 to 1259, SEQ ID NOs: 34613 to 35107, SEQ ID NO: 58050, and SEQ ID NOs: 61259 to 61262. In some embodiments, any one of the peptides in the TP53 V272M composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 739 to 755, SEQ ID NOs: 1256 to 1259, SEQ ID NOs: 34613 to 35107, SEQ ID NO: 58050, or SEQ ID NOs: 61259 to 61262. [2364] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 Y163C protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 Y163C protein mutation comprises one or more of the SEQ ID NOs: 756 to 772, SEQ ID NO: 833, SEQ ID NOs: 1260 to 1269, SEQ ID NOs: 35108 to 36047, SEQ ID NOs: 58051 to 60804, and SEQ ID NOs: 61263 to 61271. In some embodiments, any one of the peptides in the TP53 Y163C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 756 to 772, SEQ ID NO: 833, SEQ ID NOs: 1260 - 483 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 to 1269, SEQ ID NOs: 35108 to 36047, SEQ ID NOs: 58051 to 60804, or SEQ ID NOs: 61263 to 61271. [2365] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 Y205C protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 Y205C protein mutation comprises one or more of the SEQ ID NOs: 773 to 783, SEQ ID NOs: 1270 to 1279, SEQ ID NOs: 36048 to 36596, SEQ ID NOs: 60805 to 60853, and SEQ ID NOs: 61272 to 61281. In some embodiments, any one of the peptides in the TP53 Y205C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 773 to 783, SEQ ID NOs: 1270 to 1279, SEQ ID NOs: 36048 to 36596, SEQ ID NOs: 60805 to 60853, or SEQ ID NOs: 61272 to 61281. [2366] In some embodiments, the amino acid sequence for MHC class I and/or MHC class II peptides may be used to create a single target (individual) or combined peptide composition for the TP53 Y234C protein mutation having between about 2 and about 40 peptides. In some embodiments, any one of the peptides in the composition for the TP53 Y234C protein mutation comprises one or more of the SEQ ID NOs: 784 to 794, SEQ ID NO: 834, and SEQ ID NOs: 36597 to 36796. In some embodiments, any one of the peptides in the TP53 Y234C composition comprise an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NOs: 784 to 794, SEQ ID NO: 834, or SEQ ID NOs: 36597 to 36796. [2367] In some embodiments, any combination of MHC class I and/or MHC class II peptides disclosed herein (SEQ ID NOs: 1 to 61281) may be used to create a single target (individual) or combined peptide composition having between about 2 and about 40 peptides. In some embodiments, any one of the peptides (peptides 1 to 61281; SEQ ID NOs: 1 to 61281) in the combined composition comprises an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to any of SEQ ID NOs: 1 to 61281. [2368] In some embodiments, the composition comprising the MHC class I and/or MHC class II peptides disclosed herein is an immunogenic composition. In some embodiments, the composition is a vaccine. - 484 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 Table 1. Example Vaccine Peptides (MHC class I) SEQ NO SEQ NO: SEQ NO: SEQ NO: 10- SEQ NO: SEQ NO: 10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: 10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ
_ p p , NO: 35 D32G G NO: 3061 MHCflurry) - 485 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: SEQ NO: (10- SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: (10- SEQ NO: SEQ NO: (10- SEQ NO: (10- SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ
_ p p , NO: 70 S33F IH NO: 4536 NetMHCpan) SEQ ID QQSYLDFGIM CTNNB1 QQSYLDFG SEQ ID - H10M Individual CTNNB1_S33F Vaccine (10-peptide, NO: 71 S33F IH NO: 4536 NetMHCpan) - 486 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: (10- SEQ NO: SEQ NO: (10- SEQ NO: SEQ NO:
- 487 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO:
- 488 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 10-
- 489 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ
_ , NO: 225 V C420R NL NO: 804 NetMHCpan) - 490 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: SEQ NO:
- 491 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: e (10- SEQ NO: SEQ NO: e (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: e (10- SEQ NO: SEQ
_ , NO: 302 G118D NO: 12936 MHCflurry) - 492 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: e SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: e SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: e (10- SEQ NO: e (10- SEQ NO: SEQ NO: SEQ NO: e (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO:
- 493 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: e (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO:
- 494 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO:
- 495 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO:
- 496 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO:
- 497 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO:
- 498 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: - SEQ NO: SEQ NO: - SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO:
- 499 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: - SEQ NO: - SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: - SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ
_ , NO: 614 Y P151S GTR NO: 26734 MHCflurry) - 500 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ
_ , NO: 654 R249S NO: 31026 NetMHCpan) - 501 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ
_ , NO: 693 S127Y A NO: 32933 MHCflurry) - 502 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: - SEQ NO: - SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ
_ , NO: 733 V157F R NO: 34604 MHCflurry) - 503 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO:
- 504 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10- SEQ NO: (10- SEQ NO: (10- SEQ NO: SEQ NO: (10- SEQ NO: 10- SEQ NO: 10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: (10-
- 505 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: SEQ NO: e (10- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: 0- SEQ NO: SEQ NO: SEQ NO: Tab SEQ NO SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO:
tide) - 506 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide)
- 507 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: tide) SEQ NO: ide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO:
_ L A 60902 S37F L 38488 TA Vaccine (10-peptide) - 508 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide)
- 509 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide)
- 510 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide)
- 511 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide)
- 512 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: tide) SEQ NO: 1000 tide) SEQ NO: 1001 tide) SEQ NO: 1002 tide) SEQ NO: 1003 tide) SEQ NO: 1004 tide) SEQ NO: 1005 tide) SEQ NO: D 1006 tide) SEQ NO: D 1007 tide) SEQ NO: D 1008 tide) SEQ NO: D 1009 tide) SEQ NO: D 1010 tide) SEQ NO: D 1011 tide) SEQ NO: D 1012 tide) SEQ NO: D 1013 tide) SEQ NO: D 1014 tide) SEQ NO: D 1015
tide) D - 513 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: L 1016 tide) SEQ NO: L 1017 tide) SEQ NO: L 1018 tide) SEQ NO: L 1019 tide) SEQ NO: L 1020 tide) SEQ NO: L 1021 tide) SEQ NO: L 1022 tide) SEQ NO: L 1023 tide) SEQ NO: L 1024 tide) SEQ NO: L 1025 tide) SEQ NO: K 1026 tide) SEQ NO: K 1027 tide) SEQ NO: K 1028 tide) SEQ NO: K 1029 tide) SEQ NO: K 1030 tide) SEQ NO: K 1031 tide) SEQ NO: K 1032 tide) SEQ NO: K 1033 tide) SEQ NO: K 1034 tide) SEQ NO: K 1035 tide) SEQ NO:
_ K 1036 I 61045 49389 LWS Vaccine (10-peptide) - 514 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: K 1037 tide) SEQ NO: K 1038 tide) SEQ NO: K 1039 tide) SEQ NO: K 1040 tide) SEQ NO: K 1041 tide) SEQ NO: K 1042 tide) SEQ NO: K 1043 tide) SEQ NO: K 1044 tide) SEQ NO: K 1045 tide) SEQ NO: R 1046 tide) SEQ NO: R 1047 tide) SEQ NO: R 1048 tide) SEQ NO: R 1049 tide) SEQ NO: R 1050 tide) SEQ NO: R 1051 tide) SEQ NO: R 1052 tide) SEQ NO: R 1053 tide) SEQ NO: R 1054 tide) SEQ NO: R 1055 tide) SEQ NO: 1056 tide) SEQ NO: 1057
tide) LN LN - 515 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 1058 tide) SEQ NO: 1059 tide) SEQ NO: 1060 tide) SEQ NO: 1061 tide) SEQ NO: 1062 tide) SEQ NO: 1063 tide) SEQ NO: 1064 tide) SEQ NO: 1065 tide) SEQ NO: 1066 tide) SEQ NO: 1067 tide) SEQ NO: 1068 tide) SEQ NO: 1069 tide) SEQ NO: 1070 tide) SEQ NO: 1071 tide) SEQ NO: 1072 tide) SEQ NO: 1073 tide) SEQ NO: 1074 tide) SEQ NO: 1075 tide) SEQ NO: 1076 tide) SEQ NO: 1077 tide) SEQ NO: 1078 tide) SEQ NO: 1079 tide) SEQ NO: 1080 tide) SEQ NO:
_ 1081 HE V 61085 E 49665 RYP Vaccine (10-peptide) - 516 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 1082 tide) SEQ NO: 1083 tide) SEQ NO: 1084 tide) SEQ NO: 1085 tide) SEQ NO: 1086 tide) SEQ NO: 1087 tide) SEQ NO: 1088 tide) SEQ NO: 1089 tide) SEQ NO: 1090 tide) SEQ NO: 1091 tide) SEQ NO: 1092 tide) SEQ NO: 1093 tide) SEQ NO: 1094 tide) SEQ NO: 1095 tide) SEQ NO: 1096 tide) SEQ NO: 1097 tide) SEQ NO: 1098 tide) SEQ NO: 1099 tide) SEQ NO: 1100 tide) SEQ NO: 1101 tide) SEQ NO: 1102 tide) SEQ NO: 1103 tide) SEQ NO: 1104 tide) SEQ NO: 1105 tide) SEQ NO: 1106 tide) SEQ NO:
: : _ 1107 61111 50552 RPI Vaccine (10-peptide) - 517 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 1108 tide) SEQ NO: 1109 tide) SEQ NO: 1110 tide) SEQ NO: 1111 tide) SEQ NO: 1112 tide) SEQ NO: 1113 tide) SEQ NO: 1114 tide) SEQ NO: 1115 tide) SEQ NO: 1116 tide) SEQ NO: 1117 tide) SEQ NO: 1118 tide) SEQ NO: 1119 tide) SEQ NO: 1120 tide) SEQ NO: 1121 tide) SEQ NO: 1122 tide) SEQ NO: 1123 tide) SEQ NO: 1124 tide) SEQ NO: 1125 tide) SEQ NO: 1126 tide) SEQ NO: 1127 tide) SEQ NO: 1128 tide) SEQ NO: 1129 tide) SEQ NO: 1130 tide) SEQ NO: 1131 tide) SEQ NO: 1132 tide) SEQ NO: 1133 tide) SEQ NO: 1134 tide)
- 518 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 1135 tide) SEQ NO: 1136 tide) SEQ NO: 1137 tide) SEQ NO: 1138 tide) SEQ NO: 1139 tide) SEQ NO: 1140 tide) SEQ NO: 1141 tide) SEQ NO: 1142 tide) SEQ NO: 1143 tide) SEQ NO: 1144 tide) SEQ NO: 1145 tide) SEQ NO: 1146 tide) SEQ NO: 1147 tide) SEQ NO: 1148 tide) SEQ NO: 1149 tide) SEQ NO: 1150 tide) SEQ NO: 1151 tide) SEQ NO: 1152 tide) SEQ NO: 1153 tide) SEQ NO: 1154 tide) SEQ NO: 1155 tide) SEQ NO: 1156 tide) SEQ NO: 1157 tide) SEQ NO: 1158 tide) SEQ NO: 1159 tide) SEQ NO: 1160 tide) SEQ NO: 1161
accne ( -peptide) - 519 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 1162 tide) SEQ NO: 1163 tide) SEQ NO: 1164 tide) SEQ NO: 1165 tide) SEQ NO: 1166 tide) SEQ NO: 1167 tide) SEQ NO: 1168 tide) SEQ NO: 1169 tide) SEQ NO: 1170 tide) SEQ NO: 1171 tide) SEQ NO: 1172 tide) SEQ NO: 1173 tide) SEQ NO: 1174 tide) SEQ NO: 1175 tide) SEQ NO: 1176 tide) SEQ NO: 1177 tide) SEQ NO: 1178 tide) SEQ NO: 1179 tide) SEQ NO: 1180 tide) SEQ NO: 1181 tide) SEQ NO: 1182 tide) SEQ NO: 1183 tide) SEQ NO: 1184 tide) SEQ NO: 1185 tide) SEQ NO: 1186 tide)
- 520 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 1187 tide) SEQ NO: 1188 tide) SEQ NO: 1189 tide) SEQ NO: 1190 tide) SEQ NO: 1191 tide) SEQ NO: 1192 tide) SEQ NO: 1193 tide) SEQ NO: 1194 tide) SEQ NO: 1195 tide) SEQ NO: 1196 tide) SEQ NO: 1197 tide) SEQ NO: 1198 tide) SEQ NO: 1199 tide) SEQ NO: 1200 tide) SEQ NO: 1201 tide) SEQ NO: 1202 tide) SEQ NO: 1203 tide) SEQ NO: 1204 tide) SEQ NO: 1205 tide) SEQ NO: 1206 tide) SEQ NO: 1207 tide) SEQ NO: 1208 tide) SEQ NO: 1209 tide) SEQ NO: 1210 tide) SEQ NO: 1211 tide) SEQ NO: 1212 tide) SEQ NO: 1213 tide)
- 521 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 1214 tide) SEQ NO: 1215 tide) SEQ NO: 1216 tide) SEQ NO: 1217 tide) SEQ NO: 1218 tide) SEQ NO: 1219 tide) SEQ NO: 1220 tide) SEQ NO: 1221 tide) SEQ NO: 1222 tide) SEQ NO: 1223 tide) SEQ NO: 1224 tide) SEQ NO: 1225 tide) SEQ NO: 1226 tide) SEQ NO: 1227 tide) SEQ NO: 1228 tide) SEQ NO: 1229 tide) SEQ NO: 1230 tide) SEQ NO: 1231 tide) SEQ NO: 1232 tide) SEQ NO: 1233 tide) SEQ NO: 1234 tide) SEQ NO: 1235 tide) SEQ NO: 1236 tide) SEQ NO: 1237 tide) SEQ NO: 1238 tide) SEQ NO: 1239 tide) SEQ NO: 1240
accne ( -peptide) - 522 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 1241 tide) SEQ NO: 1242 tide) SEQ NO: 1243 tide) SEQ NO: 1244 tide) SEQ NO: 1245 tide) SEQ NO: 1246 tide) SEQ NO: 1247 tide) SEQ NO: 1248 tide) SEQ NO: 1249 tide) SEQ NO: 1250 tide) SEQ NO: 1251 tide) SEQ NO: 1252 tide) SEQ NO: 1253 tide) SEQ NO: 1254 tide) SEQ NO: 1255 tide) SEQ NO: 1256 ide) SEQ NO: 1257 ide) SEQ NO: 1258 ide) SEQ NO: 1259 ide) SEQ NO: 1260 tide) SEQ NO: 1261 tide) SEQ NO: 1262 tide) SEQ NO: 1263 tide) SEQ NO: 1264 tide) SEQ NO: 1265 tide) SEQ NO: 1266 tide) SEQ NO: 1267
Q accne ( -peptide) - 523 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 SEQ NO: 1268 tide) SEQ NO: 1269 tide) SEQ NO: 1270 tide) SEQ NO: 1271 tide) SEQ NO: 1272 tide) SEQ NO: 1273 tide) SEQ NO: 1274 tide) SEQ NO: 1275 tide) SEQ NO: 1276 tide) SEQ NO: 1277 tide) SEQ NO: 1278 tide) SEQ NO: 1279 tide) RN [23 mol f the ated in it ore than d by r circ e of enc con PIK opti seq ter et a r HL s enco
dng te peptdes o eac C cass nto a snge construct usng non-mmunogenc - 524 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 glyc ual con TD sign [23 A) com l pep cids in le seq emb ed in a sign MR AT YV GG CV GG SG GS GG GG RIK AT FV CS TR IY VG VM CR [23 des one emb resi som 9, 10, e pep [23 com com chai
n. In some embodiments, a nucleic acid is a compound, molecule, and/or substance that is - 525 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 or c e clea resi olig nuc . In s c acid nuc in that ar RN emb h line RN [23 com NO com , 92, [23 ic acid e emb seq iden [23 disc ) or DN out 2 an In som mor or mor NA (e.g an
- 526 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 ami r 99 [23 use mR s of an i in its e can mR vac [23 des a vac Non [23 poly acid seq Os: 178 [23 ct for poly s cau by a HL mor irst plur yed by a and the emb mod e CT G,
- 527 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 CT B1 S45 [23 can effe com cid seq [23 poly ng of S mor st two adm y the som tide of t seco s I alle s I alle o ami . In som e gro [23 can effe com acid seq [23 re poly acid seq 243 to 2 EQ ID N
Os: 341 to 386. In some embodiments, the one or more polynucleotides are contained in a - 528 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 con ore poly s cau by a HL mor irst plur yed by a and the emb mod PIK , PIK PIK [23 can effe com acid seq [23 re poly acid seq 447 to 4 D NO Q ID to 664 are con y the e poly to be d adm pep e at leas
rst - 529 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 plur st one com s, the TP5 G24 , TP5 S24 [23 can effe com acid seq [23 or mor [23 seq [23 id seq SEQ [23 emb o acid emb n a subj , an adm nuc emb t leas tide of t ein the by
- 530 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 at le d or unm CT mod sele CT 1 S45 A C42 H10 F, TP5 H17 TP5 V15 s, the e emb can colo ova seq f SEQ [23 e or mor [23 sele [23 id seq SEQ [23 g one emb o acid
- 531 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [23 e or mor [23 sele or mor [23 id seq SEQ [23 g one emb o acid [23 e or mor [24 sele e or mor [24 id seq SEQ [24 g one emb o acid [24 e or mor [24 sele ne or m
- 532 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [24 id seq SEQ [24 g one emb o acid [24 e or mor [24 sele ne or m [24 id seq SEQ [24 g one emb o acid [24 e or mor [24 sele ne or m [24 id seq SEQ [24 g one
- 533 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 emb o acid [24 e or mor [24 sele de com [24 id seq SEQ [24 g one e emb o acid [24 e or mor [24 sele tide com [24 id seq SEQ [24 g one e emb o acid [24 e or mor
- 534 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [24 sele tide com [24 id seq SEQ [24 g one e emb o acid [24 e or mor [24 sele tide com [24 id seq SEQ [24 g one emb o acid [24 e or mor [24 sele tide com [24 id seq SEQ
- 535 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [24 g one e emb o acid [24 e or mor [24 sele pep [24 id seq SEQ [24 g one emb o acid [24 e or mor [24 sele pep [24 id seq SEQ [24 g one emb o acid [24 e or mor
- 536 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [24 sele pep [24 id seq SEQ [24 g one emb o acid [24 e or mor [24 sele pep [24 id seq SEQ [24 g one e emb o acid [24 e or mor [24 sele pep [24 id seq SEQ
- 537 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [24 g one emb o acid [24 e or mor [24 sele pep [24 id seq SEQ [24 g one emb o acid [24 e or mor [24 sele pep [24 id seq SEQ [24 g one emb o acid [24 e or mor
- 538 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [24 sele pep [24 id seq SEQ [24 g one emb o acid [24 e or mor [24 sele pep [24 id seq SEQ [24 g one e emb o acid [24 e or mor [24 sele pep [24 id seq SEQ
- 539 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [24 g one e emb o acid [24 e or mor [24 sele pep [24 id seq SEQ [24 g one e emb o acid [24 e or mor [24 sele pep [24 id seq SEQ [24 g one e emb o acid [24 e or mor
- 540 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [24 sele pep [24 id seq SEQ [24 g one e emb o acid [24 e or mor [24 sele pep [24 id seq SEQ [24 g one me emb o acid [24 e or mor [24 sele pep [24 id seq SEQ
- 541 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [24 g one e emb o acid [24 e or mor [24 sele pep [24 id seq SEQ [24 g one e emb o acid [24 e or mor [25 sele pep [25 id seq SEQ [25 g one e emb o acid [25 e or mor
- 542 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [25 sele pep [25 id seq SEQ [25 g one e emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ
- 543 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor
- 544 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ
- 545 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor
- 546 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ
- 547 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor
- 548 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ
- 549 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele com [25 id seq SEQ [25 g one emb o acid [25 e or mor
- 550 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ
- 551 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [25 g one emb o acid [25 e or mor [25 sele pep [25 id seq SEQ [25 g one emb o acid [25 e or mor [26 sele pep [26 id seq SEQ [26 g one emb o acid [26 e or mor
- 552 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [26 sele pep [26 id seq SEQ [26 g one emb o acid [26 e or mor [26 sele pep [26 mor [26 seq [26 id seq SEQ [26 emb o acid emb n a subj , an adm nuc emb t
- 553 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 leas pep es, whe eles diff a mod BR des is a sele CT 1 S45 A C42 H10 F, TP5 H19 , TP5 Y16 effe
ctive amount to a subject to prevent cancer. In some embodiments, the composition is administered in an effective amount to a subject to treat cancer. In some embodiments, the can ng, uter emb no acid [26 e or mor [26 sele [26 id seq SEQ [26
g one or more amino acid sequences derived from a BRAF protein mutation. In some - 554 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 emb o acid [26 e or mor [26 sele ne or m [26 id seq SEQ [26 g one emb o acid [26 e or mor [26 sele ne or m [26 id seq SEQ [26 g one emb o acid [26 e or mor
- 555 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [26 sele ne or m [26 id seq SEQ [26 g one emb o acid [26 e or mor [26 sele one or m [26 id seq SEQ [26 g one emb o acid [26 e or mor [26 sele e one [26 id seq SEQ
- 556 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [26 g one emb o acid [26 e or mor [26 sele pep [26 id seq SEQ [26 g one e emb o acid [26 e or mor [26 sele pep [26 id seq SEQ [26 g one e emb o acid [26 e or mor
- 557 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [26 sele pep [26 id seq SEQ [26 g one e emb o acid [26 e or mor [26 sele com [26 id seq SEQ [26 g one emb o acid [26 e or mor [26 sele pep [26 id seq SEQ
- 558 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [26 g one e emb o acid [26 e or mor [26 sele pep [26 id seq SEQ [26 g one emb o acid [26 e or mor [26 sele pep [26 id seq SEQ [26 g one emb o acid [266
p , p pp p p g ne or more peptides selected from the group consisting of SEQ ID NOs: 896 to 905. - 559 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [26 sele pep [26 id seq SEQ [26 g one emb o acid [26 e or mor [26 sele pep [26 id seq SEQ [26 g one e emb o acid [26 e or mor [26 sele pep [26 id seq SEQ
- 560 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [26 g one emb o acid [26 e or mor [26 sele pep [26 id seq SEQ [26 g one emb o acid [26 e or mor [26 sele pep [26 id seq SEQ [26 g one emb o acid [26 e or mor
- 561 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [26 sele pep [26 id seq SEQ [26 g one emb o acid [26 e or mor [26 sele pep [26 id seq SEQ [26 g one e emb o acid [26 e or mor [26 sele pep [26 id seq SEQ
- 562 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [26 g one e emb o acid [26 e or mor [26 sele pep [26 id seq SEQ [27 g one e emb o acid [27 e or mor [27 sele pep [27 id seq SEQ [27 g one e emb o acid [27 e or mor
- 563 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [27 sele pep [27 id seq SEQ [27 g one e emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one me emb o acid [27 e or mor [27 sele e pep [27 id sequ
g q g p g SEQ ID NOs: 1026 to 1035. - 564 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [27 g one e emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one e emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one e emb o acid [27 e or mor
- 565 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [27 sele e pep [27 id seq SEQ [27 g one e emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or mor [27 sele e pep [27 id sequ
g q g p g SEQ ID NOs: 1076 to 1085. - 566 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one emb o acid [274
p , p pp p p g ne or more peptides selected from the group consisting of SEQ ID NOs: 1096 to 1105. - 567 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ
- 568 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or
more peptides selected from the group consisting of SEQ ID NOs: 1146 to 1155. - 569 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ
- 570 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or mor
- 571 - ActiveUS 205953775
Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ
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Attorney Docket No.2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 [27 g one emb o acid [27 e or mor [27 sele e pep [27 id seq SEQ [28 g one emb o acid [28 e or mor [28 sele e pep [28 id seq SEQ [28 g one emb o acid [28 e or mor
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SEQ ID NOs: 1270 to 1279. - 574 - ActiveUS 205953775
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formulation. In some embodiments, surfactants used with the present disclosure are - 578 - ActiveUS 205953775
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drous nature is maintained. Accordingly, anhydrous compositions are preferably packaged - 579 - ActiveUS 205953775
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Ansel et al., Lippincott Williams & Wilkins; 7th edition (Oct.1, 1999). - 581 - ActiveUS 205953775
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streamlined design of heteroclitic epitopes, Vaccine, 2007, 25(29): 5330-5342. - 589 - ActiveUS 205953775
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s N, Kinzler KW, Zhou S, Vogelstein B. Direct Detection and Quantification of Neoantigens. - 592 - ActiveUS 205953775
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RNA and DNA compositions
[2369] In some embodiments, peptides are encoded as RNA (e.g., mRNA) or DNA molecules and are administered for expression in vivo as is known in the art. One example of the delivery of RNA (e.g., mRNA) in a composition is found in Kranz et al. (2016), incorporated in its entirety by reference herein. In some embodiments, vaccine peptides are encoded in more than one RNA (e.g, mRNA) or DNA molecule as is found in Sahin et al. (2017), incorporated by reference in its entirety herein. In some embodiments, vaccine peptides are encoded in a circular RNA molecule. In some embodiments, mRNA includes circular RNA. One example of encoding circular RNA is described in Wesselhoeft et al. (2018). In one embodiment, a construct comprises 20 peptides, including a ten-peptide MHC class I composition (target: PIK3CA N345K) and a ten-peptide MHC class II composition (target: PIK3CA N345K), as optimized by the procedure described herein. Peptides are prepended with a secretion signal sequence at the N-terminus and followed by an MHC class I trafficking signal (MITD) (Kreiter et al., 2008; Sahin et al., 2017). The MITD has been shown to route antigens to pathways for HLA class I and class II presentation (Kreiter et al., 2008). Here we combine all nucleic acids encoding the peptides of each MHC class into a single construct using non-immunogenic glycine/serine linkers from Sahin et al. (2017), though it is also plausible to construct individual constructs containing nucleic acids encoding single peptides with the same secretion and MITD signals as demonstrated by Kreiter et al. (2008).
[2370] In some embodiments, the amino acid sequence encoded by the RNA (e.g., mRNA) composition comprises SEQ ID NO: 61282. Underlined amino acids correspond to the signal peptide (or leader) sequence. Bolded amino acids correspond to MHC class I (8-11 amino acids in length; 10 peptides) and MHC class II (13-25 amino acids in length; 10 peptides) peptide sequences. Italicized amino acids correspond to the trafficking signal. In alternate embodiments, any number and variation of peptide sequences disclosed herein can be included in an RNA (e.g., mRNA) vaccine comprising the signal peptide sequence and the trafficking signal as shown in SEQ ID NO: 61282 below.
594
SUBSTITUTE SHEET (RULE 26)
MRVTAPRTLILLLSGALALTETWAGSGGSGGGGSGGATYVKVNIKGGSGGGGSGGAT YVKVNIRGGSGGGGSGGAVYVKVNIKGGSGGGGSGGCVTYVKVNIRGGSGGGGSGG CVTYVKVNVGGSGGGGSGGIMCATYVKVGGSGGGGSGGKLLCATYVKVGGSGGGG SGGKMLCATYVKVGGSGGGGSGGTYVKVNIRDFGGSGGGGSGGYAKVNIRDVGGS GGGGSGGRIKFLCATPVKRNIRGGSGGGGSGGRIKFLCHTFVKLNIRGGSGGGGSGG RIKFLCITRVKENIRGGSGGGGSGGRIKFLCSTFVKVNIRGGSGGGGSGGRIKILCAT FVKFNSRDLDKIGGSGGGGSGGRIKILCATYIKVSINDIAKIGGSGGGGSGGRIKILCS TRVKLNIRGGSGGGGSGGRIKINCAAYIKVAIRGGSGGGGSGGTFVKLNARDIDKIY VGGSGGGGSGGTYLKVDIKDIRKIYVGGSLGGGGSG7FG/E4GA4 VLAWVIGA WATVM CRRKSSGGKGGSYSQAASSDSAQGSDVSLTA (SEQ ID NO: 61282).
[2371] In some embodiments, a MHC class I and/or MHC class II peptide sequence includes one or more additional flanking residues found in a native context of the peptide. In some embodiments, a MHC class I and/or MHC class II peptide sequence includes five flanking resides found in a native context of a peptide on one or both ends of the peptide sequence. In some embodiments, a MHC class I and/or MHC class II peptide sequence includes 5, 6, 7, 8, 9, 10, or more flanking residues found in a native context of a peptide on one or both ends of the peptide sequence.
[2372] In some embodiments, the composition is an RNA (e.g, mRNA) composition comprising a nucleic acids sequence. In some embodiments, a nucleic acid refers to any compound, molecule, and/or substance that is or can be incorporated into an oligonucleotide chain. In some embodiments, a nucleic acid is a compound, molecule, and/or substance that is or can be incorporated into an oligonucleotide chain via a phosphodiester linkage. As will be clear from context, in some embodiments, nucleic acid refers to an individual nucleic acid residue (e.g, a nucleotide and/or nucleoside); in some embodiments, nucleic acid refers to an oligonucleotide chain comprising individual nucleic acid residues. In some embodiments, a nucleic acid is or comprises RNA; in some embodiments, a nucleic acid is or comprises DNA. In some embodiments, a nucleic acid is, comprises, or consists of one or more natural nucleic acid residues. In some embodiments, a nucleic acid is, comprises, or consists of one or more nucleic acid analogs. In some embodiments, a nucleic acid analog differs from a nucleic acid in that it does not utilize a phosphodi ester backbone. In some embodiments, RNA refers to linear RNA (e.g., mRNA). In some embodiments, RNA refers to circular RNA. In some embodiments, RNAs used in the compositions and methods described herein can include both
595
SUBSTITUTE SHEET (RULE 26)
linear and circular components (e.g., a LNP composition with both circular RNA and linear RNA)
[2373] In some embodiments, the composition is an RNA (e.g., mRNA) composition comprising a nucleic acids sequence encoding the amino acid sequence consisting of SEQ ID NO: 61282. In some embodiments, the nucleic acid sequence of the RNA (e.g., mRNA) composition encodes for an ammo acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 61282.
[2374] In some embodiments, the composition is a DNA composition comprising a nucleic acids sequence encoding the amino acid sequence consisting of SEQ ID NO: 61282. In some embodiments, the nucleic acid sequence of the DNA composition encodes for an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to SEQ ID NO: 61282.
[2375] In some embodiments, one or more MHC class I and/or MHC class II peptides disclosed herein (SEQ ID NO: 1 to 61282) can be encoded in one or more RNA (e.g., mRNA) or DNA molecules and administered for expression in vivo. In some embodiments, between about 2 and about 40 peptide sequences are encoded in one or more RNA (e.g., mRNA) constructs. In some embodiments, between about 2 and about 40 peptide sequences are encoded in one or more DNA constructs (i.e., nucleic acids encoding the amino acids sequences comprising on or more of SEQ ID NOs: 1 to 61282). In some embodiments, the amino acid sequence of the RNA (e.g., mRNA) composition or the nucleic acid sequence of the DNA composition encodes for an amino acid sequence 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 % identical to any of SEQ ID NOs: 1 to 61282.
[2376] In some embodiments, RNA (e.g., mRNA) encoded peptides disclosed herein are used as the payload of a self-amplifying RNA vaccine. In one embodiment, the RNA (e.g., mRNA) sequence encoding the composition peptides replaces one or more structural proteins of an infectious alphavirus particle as described in Geall et al. (2012), incorporated by reference in its entirety herein. As is described by Geall et al. (2012), self-amplifying RNA compositions can increase the efficiency of antigen production in vivo. In some embodiments, RNA (e.g., mRNA) encoded peptides disclosed herein are used as the payload in a non-amplifying RNA vaccine.
596
SUBSTITUTE SHEET (RULE 26)
[2377] In some embodiments, the composition comprising the nucleic acid sequences described herein is an immunogenic composition. In some embodiments, the composition is a vaccine.
Non-limiting embodiments of the subject matter
[2378] In one aspect, the invention provides for a composition comprising one or more polynucleotides encoding at least two amino acid sequences, wherein the at least two amino acid sequences are selected from the group consisting of SEQ ID NOs: 17 to 176, and SEQ ID NOs: 178 to 184.
[2379] In some embodiments, the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides. In some embodiments, an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. In some embodiments, the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. In some embodiments, each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a CTNNB1 protein. In some embodiments, the fragment of the CTNNB1 protein comprises a mutation selected from the group consisting of CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, and CTNNB1 T41I.
[2380] In another aspect, the invention provides for a method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the composition is an immunogenic composition. In some embodiments, the at least two amino acid sequences are SEQ ID NOs: 103 and 104.
[2381] In another aspect, the invention provides for composition comprising one or more polynucleotides encoding at least two amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 207 and SEQ ID NOs: 209 to 222. In some embodiments, the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least
597
SUBSTITUTE SHEET (RULE 26)
two peptides encoded by the one or more polynucleotides. In some embodiments, an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. In some embodiments, the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. In some embodiments, each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a KRAS protein. In some embodiments, the fragment of the KRAS protein comprises a mutation selected from the group consisting of KRAS A146T, KRAS A146V, and KRAS Q61H.
[2382] In another aspect, the invention provides for a method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the composition is an immunogenic composition. In some embodiments, the at least two amino acid sequences are SEQ ID NOs: 203 and 204.
[2383] In another aspect, the invention provides for a composition comprising one or more polynucleotides encoding at least two amino acid sequences, wherein the at least two amino acid sequences are selected from the group consisting of SEQ ID NOs: 223 to 240, SEQ ID NOs: 243 to 293, SEQ ID NOs: 295 to 315, SEQ ID NOs: 317 to 329, SEQ ID NOs: 331 to 339, and SEQ ID NOs: 341 to 386. In some embodiments, the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides. In some embodiments, an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. In some embodiments, the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. In some embodiments, each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a PIK3CA protein. In some embodiments, the fragment of the PIK3CA protein comprises a mutation selected from the group consisting of PIK3CA C420R,
598
SUBSTITUTE SHEET (RULE 26)
PIK3CA E453K, PIK3CA E545A, PIK3CA E726K, PIK3CA G118D, PIK3CA H1047L, PIK3CA N345K, PIK3CA Q546K, PIK3CA Q546R, and PIK3CA R108H.
[2384] In another aspect, the invention provides for a method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the composition is an immunogenic composition. In some embodiments, the at least two amino acid sequences are SEQ ID NOs: 308 and 309.
[2385] In another aspect, the invention provides for a composition comprising one or more polynucleotides encoding at least two amino acid sequences, wherein the at least two amino acid sequences are selected from the group consisting of SEQ ID NOs: 387 to 445, SEQ ID NOs: 447 to 472, SEQ ID NOs: 474 to 480, SEQ ID NOs: 482 to 500, SEQ ID NOs: 502 to 544, SEQ ID NOs: 546 to 550, SEQ ID NOs: 552 to 564, SEQ ID NOs: 566 to 582, SEQ ID NO: 584, SEQ ID NOs: 586 to 605, SEQ ID NOs: 607 to 633, SEQ ID NOs: 638 to 656, SEQ ID NOs: 659 to 664, and SEQ ID NOs: 666 to 794. In some embodiments, the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides. In some embodiments, an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. In some embodiments, the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. In some embodiments, each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a TP53 protein. In some embodiments, the fragment of the TP53 protein comprises a mutation selected from the group consisting of TP53 C176F, TP53 C176Y, TP53 C238Y, TP53 C275Y, TP53 E285K, TP53 G245S, TP53 G245V, TP53 H179Y, TP53 H193R, TP53 I195T, TP53 K132E, TP53 K132N, TP53 P151S, TP53 R213L, TP53 R249M, TP53 R249S, TP53 R273L, TP53 R280K, TP53 S127Y, TP53 S241F, TP53 V157F, TP53 V272M, TP53 Y163C, TP53 Y205C, and TP53 Y234C.
[2386] In another aspect, the invention provides for a method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the compositions described herein. In some embodiments, the
599
SUBSTITUTE SHEET (RULE 26)
composition is an immunogenic composition. In some embodiments, the at least two amino acid sequences are SEQ ID NOs: 474 and 475.
[2387] In another aspect, the invention provides for nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834.
[2388] In some embodiments, the nucleic acid sequences encode two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834.
[2389] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834.
[2390] In some embodiments, the composition is administered to a subject. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834. In some embodiments, the nucleic acid sequences are contained in a construct for in vivo expression in a subject of at least one peptide encoded by the nucleic acid sequences. In some embodiments, an administration of the nucleic acid sequences causes the at least one peptide encoded by the nucleic acid sequences to be displayed by an HLA class I molecule in the subject. In some embodiments, the administration of the nucleic acid sequences causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated protein selected from the group consisting of BRAF, CTNNB1, KRAS, PIK3CA, and TP53. In some embodiments, the one or more peptides is a modified or unmodified fragment of a protein, wherein the protein comprises a mutation selected from the group consisting of BRAF G466V, CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, CTNNB1 T41I, KRAS A146T, KRAS A146V, KRAS Q61H, PIK3CA C420R, PIK3CA E453K, PIK3CA E545A, PIK3CA E726K, PIK3CA G118D, PIK3CA H1047L, PIK3CA N345K, PIK3CA Q546K, PIK3CA Q546R, PIK3CA R108H, TP53 C176F, TP53 C176Y, TP53 C238Y, TP53 C275Y, TP53 E285K, TP53 G245S, TP53 G245V, TP53 H179Y, TP53 H193R, TP53 I195T, TP53 K132E, TP53 K132N, TP53 P151S, TP53 R213L, TP53 R249M, TP53 R249S, TP53 R273L, TP53 R280K, TP53 S127Y, TP53 S241F, TP53
600
SUBSTITUTE SHEET (RULE 26)
V157F, TP53 V272M, TP53 Y163C, TP53 Y205C, and TP53 Y234C. In some embodiments, the composition is administered in an effective amount to a subject to prevent cancer. In some embodiments, the composition is administered in an effective amount to a subject to treat cancer. In some embodiments, the cancer is selected from the group consisting of pancreas, colon, rectum, kidney, bronchus, lung, uterus, cervix, bladder, liver, stomach, brain, breast, ovary, thyroid, and skin. In some embodiments, the composition comprises nucleic acid sequences encoding at least three amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 834.
[2391] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1 to 834.
[2392] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1 to 834.
[2393] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 16.
[2394] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a BRAF protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1 to 16.
[2395] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1 to 16.
[2396] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1 to 16. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated BRAF protein.
[2397] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 17 to 184.
[2398] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 protein mutation. In some
601
SUBSTITUTE SHEET (RULE 26)
embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 17 to 184.
[2399] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 17 to 184.
[2400] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 17 to 184. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated CTNNB1 protein.
[2401] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 222.
[2402] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a KRAS protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 185 to 222.
[2403] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 185 to 222.
[2404] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 185 to 222. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated KRAS protein.
[2405] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 223 to 386.
[2406] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 223 to 386.
[2407] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 223 to 386.
602
SUBSTITUTE SHEET (RULE 26)
[2408] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 223 to 386. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated PIK3CA protein.
[2409] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 794.
[2410] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 794.
12411] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 387 to 794.
[2412] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 387 to 794. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated TP53 protein.
12413] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: I to 16.
[2414] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a BRAF G466V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 16.
12415] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1 to 16.
[2416] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1 to 16. In some embodiments, the peptide composition comprises a peptide derived from a BRAF G466V protein mutation.
[2417] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 17 to 36.
603
SUBSTITUTE SHEET (RULE 26)
[2418] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 D32G protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 17 to 36.
[2419] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 17 to 36.
[2420] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 17 to 36. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 D32G protein mutation.
[2421] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 37 to 52.
[2422] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 G34E protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 37 to 52.
[2423] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 37 to 52.
[2424] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 37 to 52. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 G34E protein mutation.
[2425] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 53 to 67.
[2426] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 S33C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 53 to 67.
[2427] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 53 to 67.
604
SUBSTITUTE SHEET (RULE 26)
[2428] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 53 to 67. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S33C protein mutation.
[2429] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 68 to 86.
[2430] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 S33F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 68 to 86.
12431] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 68 to 86.
[2432] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 68 to 86. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S33F protein mutation.
[2433] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 87 to 102.
[2434] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 S37C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 87 to 102.
[2435] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 87 to 102.
[2436] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 87 to 102. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S37C protein mutation.
[2437] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 103 to 119.
605
SUBSTITUTE SHEET (RULE 26)
[2438] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S37F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 103 to 119.
[2439] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 103 to 119.
[2440] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 103 to 119. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S37F protein mutation.
[2441] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 120 to 134.
[2442] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 S45F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 120 to 134.
[2443] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 120 to 134.
[2444] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 120 to 134. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S45F protein mutation.
[2445] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 135 to 150.
[2446] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 S45P protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 135 to 150.
[2447] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 135 to 150.
606
SUBSTITUTE SHEET (RULE 26)
[2448] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 135 to 150. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S45P protein mutation.
[2449] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 151 to 167.
[2450] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 T41A protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 151 to 167.
12451] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 151 to 167.
[2452] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 151 to 167. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 T41 A protein mutation.
[2453] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 168 to 184.
[2454] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 T41I protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 168 to 184.
[2455] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 168 to 184.
[2456] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 168 to 184. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 T41I protein mutation.
[2457] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 193.
607
SUBSTITUTE SHEET (RULE 26)
[2458] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS A146T protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 185 to 193.
[2459] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 185 to 193.
[2460] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 185 to 193. In some embodiments, the peptide composition comprises a peptide derived from a KRAS A146T protein mutation.
[2461] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 194 to 202.
[2462] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a KRAS A146V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 194 to 202.
[2463] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 194 to 202.
[2464] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 194 to 202. In some embodiments, the peptide composition comprises a peptide derived from a KRAS A146V protein mutation.
[2465] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 203 to 222.
[2466] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a KRAS Q61H protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 203 to 222.
[2467] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 203 to 222.
608
SUBSTITUTE SHEET (RULE 26)
[2468] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 203 to 222. In some embodiments, the peptide composition comprises a peptide derived from a KRAS Q61H protein mutation.
[2469] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 223 to 239.
[2470] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA C420R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 223 to 239.
[2471] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 223 to 239.
[2472] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 223 to 239. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA C420R protein mutation.
[2473] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 240 to 255.
[2474] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA E453K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 240 to 255.
[2475] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 240 to 255.
[2476] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 240 to 255. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E453K protein mutation.
[2477] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 256 to 271.
609
SUBSTITUTE SHEET (RULE 26)
[2478] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E545A protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 256 to 271.
[2479] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 256 to 271.
[2480] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 256 to 271. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E545A protein mutation.
[2481] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 272 to 290.
[2482] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA E726K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 272 to 290.
[2483] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 272 to 290.
[2484] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 272 to 290. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E726K protein mutation.
[2485] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 291 to 307.
[2486] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA G118D protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 291 to 307.
[2487] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 291 to 307.
610
SUBSTITUTE SHEET (RULE 26)
[2488] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 291 to 307. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA G118D protein mutation.
[2489] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 308 to 325.
[2490] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA H1047L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 308 to 325.
[2491] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 308 to 325.
[2492] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 308 to 325. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA H1047L protein mutation.
[2493] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 326 to 339.
[2494] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA N345K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 326 to 339.
[2495] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 326 to 339.
[2496] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 326 to 339. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA N345K protein mutation.
[2497] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 340 to 358.
611
SUBSTITUTE SHEET (RULE 26)
[2498] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA Q546K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 340 to 358.
[2499] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 340 to 358.
[2500] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 340 to 358. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA Q546K protein mutation.
[2501] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 359 to 376.
[2502] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA Q546R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 359 to 376.
[2503] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 359 to 376.
[2504] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 359 to 376. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA Q546R protein mutation.
[2505] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 377 to 386.
[2506] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA R108H protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 377 to 386.
[2507] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 377 to 386.
612
SUBSTITUTE SHEET (RULE 26)
[2508] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 377 to 386. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA R108H protein mutation.
[2509] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 403.
[2510] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 C176F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 387 to 403.
12511] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 387 to 403.
[2512] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 387 to 403. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C176F protein mutation.
[2513] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 404 to 420.
12514] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 C176Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 404 to 420.
[2515] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 404 to 420.
[2516] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 404 to 420. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C176Y protein mutation.
[2517] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 421 to 440.
613
SUBSTITUTE SHEET (RULE 26)
[2518] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C238Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 421 to 440.
[2519] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 421 to 440.
[2520] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 421 to 440. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C238Y protein mutation.
[2521] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 441 to 457.
[2522] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C275Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 441 to 457.
[2523] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 441 to 457.
[2524] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 441 to 457. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C275Y protein mutation.
[2525] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 458 to 473.
[2526] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 E285K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 458 to 473.
[2527] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 458 to 473.
614
SUBSTITUTE SHEET (RULE 26)
[2528] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 458 to 473. In some embodiments, the peptide composition comprises a peptide derived from a TP53 E285K protein mutation.
[2529] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 474 to 492.
[2530] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 G245S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 474 to 492.
[2531] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 474 to 492.
[2532] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 474 to 492. In some embodiments, the peptide composition comprises a peptide derived from a TP53 G245S protein mutation.
[2533] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 493 to 511.
[2534] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 G245V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 493 to 511.
[2535] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 493 to 511.
[2536] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 493 to 511. In some embodiments, the peptide composition comprises a peptide derived from a TP53 G245V protein mutation.
[2537] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 512 to 529.
615
SUBSTITUTE SHEET (RULE 26)
[2538] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 H179Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 512 to 529.
[2539] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 512 to 529.
[2540] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 512 to 529. In some embodiments, the peptide composition comprises a peptide derived from a TP53 H179Y protein mutation.
12541] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 530 to 546.
[2542] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 H193R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 530 to 546.
[2543] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 530 to 546.
[2544] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 530 to 546. In some embodiments, the peptide composition comprises a peptide derived from a TP53 H193R protein mutation.
[2545] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 547 to 563.
[2546] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 I195T protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 547 to 563.
[2547] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 547 to 563.
616
SUBSTITUTE SHEET (RULE 26)
[2548] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 547 to 563. In some embodiments, the peptide composition comprises a peptide derived from a TP53 I195T protein mutation.
[2549] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 564 to 582.
[2550] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 K132E protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 564 to 582.
[2551] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 564 to 582.
[2552] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 564 to 582. In some embodiments, the peptide composition comprises a peptide derived from a TP53 K132E protein mutation.
[2553] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 583 to 599.
[2554] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 K132N protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 583 to 599.
[2555] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 583 to 599.
[2556] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 583 to 599. In some embodiments, the peptide composition comprises a peptide derived from a TP53 K132N protein mutation.
[2557] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 600 to 614.
617
SUBSTITUTE SHEET (RULE 26)
[2558] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 P151S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 600 to 614.
[2559] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 600 to 614.
[2560] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 600 to 614. In some embodiments, the peptide composition comprises a peptide derived from a TP53 P151S protein mutation.
[2561] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 615 to 631.
[2562] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 R213L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 615 to 631.
[2563] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 615 to 631.
[2564] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 615 to 631. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R213L protein mutation.
[2565] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 632 to 648.
[2566] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 R249M protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 632 to 648.
[2567] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 632 to 648.
618
SUBSTITUTE SHEET (RULE 26)
[2568] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 632 to 648. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R249M protein mutation.
[2569] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 649 to 665.
[2570] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 R249S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 649 to 665.
[2571] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 649 to 665.
[2572] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 649 to 665. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R249S protein mutation.
[2573] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 666 to 680.
[2574] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 R273L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 666 to 680.
[2575] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 666 to 680.
[2576] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 666 to 680. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R273L protein mutation.
[2577] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NO: 681.
619
SUBSTITUTE SHEET (RULE 26)
[2578] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R280K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NO: 681.
[2579] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NO: 681.
[2580] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NO: 681. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R280K protein mutation.
[2581] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 682 to 700.
[2582] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 S127Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 682 to 700.
[2583] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 682 to 700.
[2584] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 682 to 700. In some embodiments, the peptide composition comprises a peptide derived from a TP53 S127Y protein mutation.
[2585] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 701 to 718.
[2586] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 S241F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 701 to 718.
[2587] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 701 to 718.
620
SUBSTITUTE SHEET (RULE 26)
[2588] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 701 to 718. In some embodiments, the peptide composition comprises a peptide derived from a TP53 S241F protein mutation.
[2589] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 719 to 738.
[2590] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 V157F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 719 to 738.
[2591] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 719 to 738.
[2592] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 719 to 738. In some embodiments, the peptide composition comprises a peptide derived from a TP53 V157F protein mutation.
[2593] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 739 to 755.
[2594] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 V272M protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 739 to 755.
[2595] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 739 to 755.
[2596] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 739 to 755. In some embodiments, the peptide composition comprises a peptide derived from a TP53 V272M protein mutation.
[2597] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 756 to 772.
621
SUBSTITUTE SHEET (RULE 26)
[2598] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 Y163C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 756 to 772.
[2599] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 756 to 772.
[2600] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 756 to 772. In some embodiments, the peptide composition comprises a peptide derived from a TP53 Y163C protein mutation.
[2601] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 773 to 783.
[2602] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 Y205C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 773 to 783.
[2603] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 773 to 783.
[2604] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 773 to 783. In some embodiments, the peptide composition comprises a peptide derived from a TP53 Y205C protein mutation.
[2605] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 784 to 794.
[2606] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 Y234C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 784 to 794.
[2607] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 784 to 794.
622
SUBSTITUTE SHEET (RULE 26)
[2608] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 784 to 794. In some embodiments, the peptide composition comprises a peptide derived from a TP53 Y234C protein mutation.
[2609] In one aspect, the invention provides for nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279.
[2610] In some embodiments, the nucleic acid sequences encode two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279.
[2611] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279.
[2612] In some embodiments, the composition is administered to a subject. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279. In some embodiments, the nucleic acid sequences are contained in a construct for in vivo expression in a subject of at least one peptide encoded by the nucleic acid sequences. In some embodiments, an administration of the nucleic acid sequences causes the at least one peptide encoded by the nucleic acid sequences to be displayed by an HLA class II molecule in the subject. In some embodiments, the administration of the nucleic acid sequences causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class II alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class II alleles, wherein the first plurality of HLA class II alleles and the second plurality of HLA class II alleles differ by at least one HLA class II allele. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated protein selected from the group consisting of BRAF, CTNNB1, KRAS, PIK3CA, and TP53. In some embodiments, the one or more peptides is a modified or unmodified fragment of a protein, wherein the protein comprises a mutation selected from the group consisting of BRAF G466V, CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, CTNNB1 T41I, KRAS A146T, KRAS A146V, KRAS Q61H, PIK3CA C420R, PIK3CA E453K, PIK3CA E545A, PIK3CA E726K, PIK3CA G118D, PIK3CA H1047L, PIK3CA N345K, PIK3CA Q546K, PIK3CA Q546R, PIK3CA R108H, TP53 C176F, TP53 C176Y, TP53 C238Y, TP53 C275Y, TP53 G245S, TP53 G245V, TP53 H179Y, TP53 H193R, TP53 I195T, TP53 K132E, TP53 K132N, TP53 P151S, TP53 R213L, TP53 R249M,
623
SUBSTITUTE SHEET (RULE 26)
TP53 R249S, TP53 R273L, TP53 S127Y, TP53 S241F, TP53 V157F, TP53 V272M, TP53 Y163C, and TP53 Y205C. In some embodiments, the composition is administered in an effective amount to a subject to prevent cancer. In some embodiments, the composition is administered in an effective amount to a subject to treat cancer. In some embodiments, the cancer is selected from the group consisting of pancreas, colon, rectum, kidney, bronchus, lung, uterus, cervix, bladder, liver, stomach, brain, breast, ovary, thyroid, and skin. In some embodiments, the composition comprises nucleic acid sequences encoding at least three amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 1279.
[2613] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 835 to 1279.
[2614] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 835 to 1279.
[2615] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 844.
[2616] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a BRAF protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 835 to 844.
[2617] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 835 to 844.
[2618] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 835 to 844. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated BRAF protein.
[2619] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 845 to 935.
[2620] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 protein mutation. In some
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SUBSTITUTE SHEET (RULE 26)
embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 845 to 935.
[2621] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 845 to 935.
[2622] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 845 to 935. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated CTNNB1 protein.
[2623] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 936 to 965.
[2624] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a KRAS protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 936 to 965.
[2625] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 936 to 965.
[2626] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 936 to 965. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated KRAS protein.
[2627] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 966 to 1065.
[2628] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 966 to 1065.
[2629] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 966 to 1065.
625
SUBSTITUTE SHEET (RULE 26)
[2630] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 966 to 1065. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated PIK3CA protein.
[2631] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1066 to 1279.
[2632] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1066 to 1279.
[2633] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1066 to 1279.
[2634] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1066 to 1279. In some embodiments, the one or more peptides is a modified or unmodified fragment of a mutated TP53 protein.
[2635] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 844.
[2636] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a BRAF G466V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 835 to 844.
[2637] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 835 to 844.
[2638] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 835 to 844. In some embodiments, the peptide composition comprises a peptide derived from a BRAF G466V protein mutation.
[2639] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 845 to 854.
626
SUBSTITUTE SHEET (RULE 26)
[2640] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 D32G protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 845 to 854.
[2641] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 845 to 854.
[2642] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 845 to 854. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 D32G protein mutation.
[2643] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 855 to 864.
[2644] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 G34E protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 855 to 864.
[2645] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 855 to 864.
[2646] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 855 to 864. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 G34E protein mutation.
[2647] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NO: 865.
[2648] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 S33C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NO: 865.
[2649] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NO: 865.
627
SUBSTITUTE SHEET (RULE 26)
[2650] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NO: 865. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S33C protein mutation.
[2651] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 866 to 875.
[2652] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 S33F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 866 to 875.
[2653] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 866 to 875.
[2654] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 866 to 875. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S33F protein mutation.
[2655] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 876 to 885.
[2656] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 S37C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 876 to 885.
[2657] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 876 to 885.
[2658] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 876 to 885. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S37C protein mutation.
[2659] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 886 to 895.
628
SUBSTITUTE SHEET (RULE 26)
[2660] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a CTNNB1 S37F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 886 to 895.
[2661] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 886 to 895.
[2662] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 886 to 895. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S37F protein mutation.
[2663] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 896 to 905.
[2664] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 S45F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 896 to 905.
[2665] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 896 to 905.
[2666] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 896 to 905. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S45F protein mutation.
[2667] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 906 to 915.
[2668] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 S45P protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 906 to 915.
[2669] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 906 to 915.
629
SUBSTITUTE SHEET (RULE 26)
[2670] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 906 to 915. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 S45P protein mutation.
[2671] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 916 to 925.
[2672] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 T41A protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 916 to 925.
[2673] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 916 to 925.
[2674] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 916 to 925. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 T41 A protein mutation.
[2675] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 926 to 935.
[2676] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a CTNNB1 T41I protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 926 to 935.
[2677] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 926 to 935.
[2678] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 926 to 935. In some embodiments, the peptide composition comprises a peptide derived from a CTNNB1 T41I protein mutation.
[2679] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 936 to 945.
630
SUBSTITUTE SHEET (RULE 26)
[2680] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a KRAS A146T protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 936 to 945.
[2681] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 936 to 945.
[2682] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 936 to 945. In some embodiments, the peptide composition comprises a peptide derived from a KRAS A146T protein mutation.
[2683] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 946 to 955.
[2684] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a KRAS A146V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 946 to 955.
[2685] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 946 to 955.
[2686] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 946 to 955. In some embodiments, the peptide composition comprises a peptide derived from a KRAS A146V protein mutation.
[2687] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 956 to 965.
[2688] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a KRAS Q61H protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 956 to 965.
[2689] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 956 to 965.
631
SUBSTITUTE SHEET (RULE 26)
[2690] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 956 to 965. In some embodiments, the peptide composition comprises a peptide derived from a KRAS Q61H protein mutation.
[2691] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 966 to 975.
[2692] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA C420R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 966 to 975.
[2693] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 966 to 975.
[2694] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 966 to 975. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA C420R protein mutation.
[2695] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 976 to 985.
[2696] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA E453K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 976 to 985.
[2697] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 976 to 985.
[2698] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 976 to 985. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E453K protein mutation.
[2699] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 986 to 995.
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SUBSTITUTE SHEET (RULE 26)
[2700] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA E545A protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 986 to 995.
[2701] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 986 to 995.
[2702] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 986 to 995. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E545A protein mutation.
[2703] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 996 to 1005.
[2704] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA E726K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 996 to 1005.
[2705] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 996 to 1005.
[2706] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 996 to 1005. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA E726K protein mutation.
[2707] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1006 to 1015.
[2708] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA G118D protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1006 to 1015.
[2709] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1006 to 1015.
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SUBSTITUTE SHEET (RULE 26)
[2710] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1006 to 1015. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA G118D protein mutation.
[2711] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1016 to 1025.
[2712] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA H1047L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1016 to 1025.
[2713] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1016 to 1025.
[2714] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1016 to 1025. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA H1047L protein mutation.
[2715] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1026 to 1035.
[2716] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA N345K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1026 to 1035.
[2717] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1026 to 1035.
[2718] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1026 to 1035. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA N345K protein mutation.
[2719] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1036 to 1045.
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SUBSTITUTE SHEET (RULE 26)
[2720] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a PIK3CA Q546K protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1036 to 1045.
[2721] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1036 to 1045.
[2722] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1036 to 1045. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA Q546K protein mutation.
[2723] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1046 to 1055.
[2724] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA Q546R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1046 to 1055.
[2725] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1046 to 1055.
[2726] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1046 to 1055. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA Q546R protein mutation.
[2727] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1056 to 1065.
[2728] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a PIK3CA R108H protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1056 to 1065.
[2729] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1056 to 1065.
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SUBSTITUTE SHEET (RULE 26)
[2730] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1056 to 1065. In some embodiments, the peptide composition comprises a peptide derived from a PIK3CA R108H protein mutation.
[2731] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1066 to 1075.
[2732] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 C176F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1066 to 1075.
[2733] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1066 to 1075.
[2734] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1066 to 1075. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C176F protein mutation.
[2735] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1076 to 1085.
[2736] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 C176Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1076 to 1085.
[2737] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1076 to 1085.
[2738] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1076 to 1085. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C176Y protein mutation.
[2739] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1086 to 1095.
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SUBSTITUTE SHEET (RULE 26)
[2740] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C238Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1086 to 1095.
[2741] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1086 to 1095.
[2742] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1086 to 1095. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C238Y protein mutation.
[2743] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1096 to 1105.
[2744] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 C275Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1096 to 1105.
[2745] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1096 to 1105.
[2746] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1096 to 1105. In some embodiments, the peptide composition comprises a peptide derived from a TP53 C275Y protein mutation.
[2747] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1106 to 1115.
[2748] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 G245S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1106 to 1115.
[2749] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1106 to 1115.
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SUBSTITUTE SHEET (RULE 26)
[2750] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1106 to 1115. In some embodiments, the peptide composition comprises a peptide derived from a TP53 G245S protein mutation.
[2751] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1116 to 1125.
[2752] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 G245V protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1116 to 1125.
[2753] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1116 to 1125.
[2754] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1116 to 1125. In some embodiments, the peptide composition comprises a peptide derived from a TP53 G245V protein mutation.
[2755] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1126 to 1135.
[2756] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 H179Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1126 to 1135.
[2757] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1126 to 1135.
[2758] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1126 to 1135. In some embodiments, the peptide composition comprises a peptide derived from a TP53 H179Y protein mutation.
[2759] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1136 to 1145.
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SUBSTITUTE SHEET (RULE 26)
[2760] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 H193R protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1136 to 1145.
[2761] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1136 to 1145.
[2762] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1136 to 1145. In some embodiments, the peptide composition comprises a peptide derived from a TP53 H193R protein mutation.
[2763] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1146 to 1155.
[2764] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 I195T protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1146 to 1155.
[2765] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1146 to 1155.
[2766] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1146 to 1155. In some embodiments, the peptide composition comprises a peptide derived from a TP53 I195T protein mutation.
[2767] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1156 to 1165.
[2768] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 K132E protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1156 to 1165.
[2769] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1156 to 1165.
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SUBSTITUTE SHEET (RULE 26)
[2770] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1156 to 1165. In some embodiments, the peptide composition comprises a peptide derived from a TP53 K132E protein mutation.
[2771] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1166 to 1175.
[2772] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 K132N protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1166 to 1175.
[2773] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1166 to 1175.
[2774] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1166 to 1175. In some embodiments, the peptide composition comprises a peptide derived from a TP53 K132N protein mutation.
[2775] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1176 to 1185.
[2776] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 P151S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1176 to 1185.
[2777] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1176 to 1185.
[2778] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1176 to 1185. In some embodiments, the peptide composition comprises a peptide derived from a TP53 P151S protein mutation.
[2779] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1186 to 1195.
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SUBSTITUTE SHEET (RULE 26)
[2780] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 R213L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1186 to 1195.
[2781] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1186 to 1195.
[2782] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1186 to 1195. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R213L protein mutation.
[2783] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1196 to 1205.
[2784] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 R249M protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1196 to 1205.
[2785] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1196 to 1205.
[2786] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1196 to 1205. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R249M protein mutation.
[2787] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1206 to 1215.
[2788] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 R249S protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1206 to 1215.
[2789] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1206 to 1215.
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SUBSTITUTE SHEET (RULE 26)
[2790] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1206 to 1215. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R249S protein mutation.
[2791] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1216 to 1225.
[2792] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 R273L protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1216 to 1225.
[2793] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1216 to 1225.
[2794] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1216 to 1225. In some embodiments, the peptide composition comprises a peptide derived from a TP53 R273L protein mutation.
[2795] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1226 to 1235.
[2796] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 S127Y protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1226 to 1235.
[2797] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1226 to 1235.
[2798] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1226 to 1235. In some embodiments, the peptide composition comprises a peptide derived from a TP53 S127Y protein mutation.
[2799] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1236 to 1245.
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SUBSTITUTE SHEET (RULE 26)
[2800] In some embodiments, the composition comprises nucleic acid sequences encoding one or more amino acid sequences derived from a TP53 S241F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1236 to 1245.
[2801] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1236 to 1245.
[2802] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1236 to 1245. In some embodiments, the peptide composition comprises a peptide derived from a TP53 S241F protein mutation.
[2803] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1246 to 1255.
[2804] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 V157F protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1246 to 1255.
[2805] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1246 to 1255.
[2806] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1246 to 1255. In some embodiments, the peptide composition comprises a peptide derived from a TP53 V157F protein mutation.
[2807] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1256 to 1259.
[2808] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 V272M protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more ammo acid sequences selected from the group consisting of SEQ ID NOs: 1256 to 1259.
[2809] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1256 to 1259.
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SUBSTITUTE SHEET (RULE 26)
[2810] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1256 to 1259. In some embodiments, the peptide composition comprises a peptide derived from a TP53 V272M protein mutation.
[2811] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1260 to 1269.
[2812] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 Y163C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1260 to 1269.
[2813] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1260 to 1269.
[2814] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1260 to 1269. In some embodiments, the peptide composition comprises a peptide derived from a TP53 Y163C protein mutation.
[2815] In another aspect, the invention provides for a composition comprising nucleic acid sequences encoding one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1270 to 1279.
[2816] In some embodiments, the composition comprises nucleic acid sequences encoding one or more ammo acid sequences derived from a TP53 Y205C protein mutation. In some embodiments, the composition comprises nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1270 to 1279.
[2817] In another aspect, the invention provides for a peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NOs: 1270 to 1279.
[2818] In some embodiments, the peptide composition comprises two or more peptides selected from the group consisting of SEQ ID NOs: 1270 to 1279. In some embodiments, the peptide composition comprises a peptide derived from a TP53 Y205C protein mutation.
[2819] In some embodiments, the compositions, including peptide compositions, of the invention are immunogenic compositions. To this end, the invention provides for a method of
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SUBSTITUTE SHEET (RULE 26)
inducing an immunogenic response in a subject comprising administering to the subject a composition of the invention.
[2820] In some embodiments, compositions, including peptide compositions, of the invention are vaccines.
Compositions
[2821] In some embodiments, the nucleic acid sequences of this disclosure are administered in a composition. In some embodiments, the nucleic acid sequences of this disclosure are administered in a pharmaceutical composition that includes a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition is in the form of a spray, aerosol, gel, solution, emulsion, lipid nanoparticle, nanoparticle, or suspension. In some embodiments, the composition or pharmaceutical composition is in the form of a cationic nanoemulsion, one example of which is described by Brito et al. (2014) that is incorporated herein by reference.
[2822] In some embodiments, the one or more peptides of this disclosure are administered in a composition. In some embodiments, the one or more peptides of this disclosure are administered in a pharmaceutical composition that includes a pharmaceutically acceptable carrier. In some embodiments, the composition or pharmaceutical composition is comprised of the third peptide set, as described in this disclosure. In some embodiments, the pharmaceutical composition is in the form of a spray, aerosol, gel, solution, emulsion, lipid nanoparticle, nanoparticle, or suspension. In some embodiments, the composition pharmaceutical composition is in the form of a cationic nanoemulsion, one example of which is described by Brito et al. (2014) that is incorporated herein by reference.
[2823] The composition is preferably administered to a subject with a pharmaceutically acceptable carrier, z.e., as a pharmaceutical composition. Typically, in some embodiments, an appropriate amount of a pharmaceutically acceptable salt is used in the formulation, which in some embodiments can render the formulation isotonic.
[2824] In certain embodiments, nucleic acid sequences are provided as an immunogenic composition comprising any one of the nucleic acid sequences described herein and a pharmaceutically acceptable carrier. In some embodiments, modified RNA is used with full substitution of 5-Methoxy-U for uracil or other nucleoside analogs are used to reduce the immunogenicity of the RNA. In some embodiments, modified RNA is used with full
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SUBSTITUTE SHEET (RULE 26)
substitution of Nl-methylpseudoundine for uracil. In some embodiments, modified RNA is used with partial substitution of Nl-methylpseudouridine for uracil to reduce the immunogenicity of the RNA with some percentage of unmodified uracil (e.g. 99% Nl- methylpseudouridine modified uracil and 1% unmodified uracil, or 99.9% Nl- methylpseudouridine modified uracil and 0. 1% unmodified uracil). In some embodiments, modified RNA is used with partial substitution of a nucleoside analog with some percentage of unmodified nucleoside (e g. 99% modified nucleoside and 1% unmodified nucleoside, or 99.9% modified nucleoside and 0.1% unmodified nucleoside). Some embodiments of modified RNA are described in US Patent 10,232,055. In some embodiments, the RNA is capped. One embodiment of capping is described in US Patent 10,494,399. In some embodiments, the RNA is poly adenylated, for example, with 120 adenosines. In some embodiments, the open reading frame of the RNA is flanked by a 5’ untranslated region (UTR) containing a strong Kozak translational initiation signal, and an alpha-globin 3’ UTR terminating with an oligo(dT) sequence for templated addition of a polyA tail as described in Warren et al., 2010. In some embodiments, linear RNA is employed to encode peptides. In some embodiments, circular RNA is employed to encode peptides. One embodiment of the use of circular RNA for vaccines is described by Li et al., 2022. One example of a method to prepare circular RNA is described in US Patent 11,203,767. In some embodiments, nucleic acid is encapsulated in lipid nanoparticles (LNPs). One embodiment of preparing lipid nanoparticles that contain RNA is described by Pardi et al., 2017. In one embodiment, to prepare mRNA-LNPs an ethanolic solution of ALC-0315 (described in Patent WO2017075531), cholesterol, distearoylphosphatidylcholine (DSPC), and 2- [(polyethylene glycol)-2000] N,N ditetradecylacetamide (ALC-0159, described in Patent Application US14732218) is rapidly mixed with a solution of RNA in citrate buffer at pH 4.0 (the composition is described in Patent W02018081480).
[2825] In certain embodiments, the peptides are provided as an immunogenic composition comprising any one of the peptides described herein and a pharmaceutically acceptable carrier. In some embodiments, a MHC class I and/or MHC class II peptide in an immunogenic composition includes one or more additional flanking residues found in a native context of the peptide. In certain embodiments, the immunogenic composition further comprises an adjuvant. In certain embodiments, the peptides are conjugated with other molecules to increase their effectiveness as is known by those practiced in the art. For example, peptides can be coupled to antibodies that recognize cell surface proteins on antigen presenting cells to enhance vaccine
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SUBSTITUTE SHEET (RULE 26)
effectiveness. One such method for increasing the effectiveness of peptide delivery is described in Woodham, et al. (2018). In certain embodiments for the treatment of autoimmune disorders, the peptides are delivered with a composition and protocol designed to induce tolerance as is known in the art. Example methods for using peptides for immune tolerization are described in Alhadj Ah, et al. (2017) and Gibson, et al. (2015).
[2826] In some embodiments, the pharmaceutically acceptable carrier is selected from the group consisting of saline, Ringer's solution, dextrose solution, and a combination thereof. Other suitable pharmaceutically acceptable carriers known in the art are contemplated. Suitable carriers and their formulations are described in Remington’s Pharmaceutical Sciences, 2005, Mack Publishing Co. The pH of the solution is preferably from about 5 to about 8, and more preferably from about 7 to about 7.5. The formulation may also comprise a lyophilized powder. Further carriers include sustained release preparations such as semipermeable matrices of solid hydrophobic polymers, which matrices are in the form of shaped articles, e.g., films, liposomes or microparticles. It will be apparent to those persons skilled in the art that certain carriers may be more preferable depending upon, for instance, the route of administration and concentration of peptides being administered.
[2827] The phrase pharmaceutically acceptable carrier as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting the subject pharmaceutical agent from one organ, or portion of the body, to another organ, or portion of the body. Each carrier is acceptable in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as com starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, com oil and soybean oil; glycols, such as butylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer’s solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations. The term carrier denotes an
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organic or inorganic ingredient, natural or synthetic, with which the active ingredient is combined to facilitate the application. The components of the pharmaceutical compositions also are capable of being comingled with the compounds of the present invention, and with each other, in a manner such that there is no interaction which would substantially impair the desired pharmaceutical efficiency. The composition may also include additional agents such as an isotonicity agent, a preservative, a surfactant, and, a divalent cation, preferably, zinc.
[2828] The composition can also include an excipient, or an agent for stabilization of a peptide composition, such as a buffer, a reducing agent, a bulk protein, amino acids (such as e.g., glycine or praline) or a carbohydrate. Bulk proteins useful in formulating peptide compositions include albumin. Typical carbohydrates useful in formulating peptides include but are not limited to sucrose, mannitol, lactose, trehalose, or glucose.
[2829] Surfactants may also be used to prevent soluble and insoluble aggregation and/or precipitation of peptides or proteins included in the composition. Suitable surfactants include but are not limited to sorbitan trioleate, soya lecithin, and oleic acid. In certain cases, solution aerosols are preferred using solvents such as ethanol. Thus, formulations including peptides can also include a surfactant that can reduce or prevent surface-induced aggregation of peptides by atomization of the solution in forming an aerosol. Various conventional surfactants can be employed, such as polyoxyethylene fatty acid esters and alcohols, and polyoxyethylene sorbitol fatty acid esters. Amounts will generally range between 0.001% and 4% by weight of the formulation. In some embodiments, surfactants used with the present disclosure are polyoxyethylene sorbitan mono-oleate, polysorbate 80, polysorbate 20. Additional agents known in the art can also be included in the composition.
[2830] In some embodiments, the compositions and dosage forms further comprise one or more compounds that reduce the rate by which an active ingredient will decay, or the composition will change in character. So-called stabilizers or preservatives may include, but are not limited to, amino acids, antioxidants, pH buffers, or salt buffers. Non-limiting examples of antioxidants include butylated hydroxy anisole (BHA), ascorbic acid and derivatives thereof, tocopherol and derivatives thereof, butylated hydroxy anisole and cysteine. Non-limiting examples of preservatives include parabens, such as methyl or propyl p-hydroxybenzoate and benzalkonium chloride. Additional non-limiting examples of amino acids include glycine or proline.
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[2831] The present invention also teaches the stabilization (preventing or minimizing thermally or mechanically induced soluble or insoluble aggregation and/or precipitation of an inhibitor protein) of liquid solutions containing peptides at neutral pH or less than neutral pH by the use of amino acids including proline or glycine, with or without divalent cations resulting in clear or nearly clear solutions that are stable at room temperature or preferred for pharmaceutical administration.
[2832] In one embodiment, the composition is of single unit or multiple unit dosage forms. Compositions of single unit or multiple unit dosage forms of the invention comprise a prophylactically or therapeutically effective amount of one or more compositions (e.g., a compound of the invention, or other prophylactic or therapeutic agent), typically, one or more vehicles, carriers, or excipients, stabilizing agents, and/or preservatives. Preferably, the vehicles, carriers, excipients, stabilizing agents and preservatives are pharmaceutically acceptable.
[2833] In some embodiments, the compositions and dosage forms comprise anhydrous compositions and dosage forms. Anhydrous compositions and dosage forms of the invention can be prepared using anhydrous or low moisture containing ingredients and low moisture or low humidity conditions. Compositions and dosage forms that comprise lactose and at least one active ingredient that comprise a primary or secondary amine are preferably anhydrous if substantial contact with moisture and/or humidity during manufacturing, packaging, and/or storage is expected. An anhydrous composition should be prepared and stored such that its anhydrous nature is maintained. Accordingly, anhydrous compositions are preferably packaged using materials known to prevent exposure to water such that they can be included in suitable formulary kits. Examples of suitable packaging include, but are not limited to, hermetically sealed foils, plastics, unit dose containers e.g., vials), blister packs, and strip packs.
[2834] Suitable vehicles are well known to those skilled in the art of pharmacy, and nonlimiting examples of suitable vehicles include glucose, sucrose, starch, lactose, gelatin, rice, silica gel, glycerol, talc, sodium chloride, dried skim milk, propylene glycol, water, sodium stearate, ethanol, and similar substances well known in the art. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid vehicles. Whether a particular vehicle is suitable for incorporation into a composition or dosage form depends on a variety of factors well known in the art including, but not limited to, the way in which the dosage form will be administered to a patient and the specific active ingredients in the dosage form.
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Pharmaceutical vehicles can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like.
[2835] The invention also provides that a composition can be packaged in a hermetically sealed container such as an ampoule or sachet indicating the quantity. In one embodiment, the composition can be supplied as a dry sterilized lyophilized powder in a delivery device suitable for administration to the lower airways of a patient. The compositions can, if desired, be presented in a pack or dispenser device that can contain one or more unit dosage forms containing the active ingredient. The pack can, for example, comprise metal or plastic foil, such as a blister pack. The pack or dispenser device can be accompanied by instructions for administration.
[2836] Methods of preparing these formulations or compositions include the step of bringing into association a compound of the present invention with the carrier and, optionally, one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association a compound of the present invention with liquid carriers, or finely divided solid earners, or both, and then, if necessary, shaping the product.
[2837] Formulations of the invention suitable for administration may be in the form of powders, granules, or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia) and/or as mouthwashes and the like, each containing a predetermined amount of a compound of the present invention (e.g., peptides) as an active ingredient.
[2838] A liquid composition herein can be used as such with a delivery device, or they can be used for the preparation of pharmaceutically acceptable formulations comprising peptides that are prepared, for example, by the method of spray drying. The methods of spray freeze- drying peptides/proteins for pharmaceutical administration disclosed in Maa et al., Curr. Pharm. Biotechnol., 2001, 1, 283-302, are incorporated herein. In another embodiment, the liquid solutions herein are freeze spray dried and the spray-dried product is collected as a dispersible peptide-containing powder that is therapeutically effective when administered to an individual.
[2839] The compounds and compositions of the present invention can be employed in combination therapies, that is, the compounds and compositions can be administered
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concurrently with, prior to, or subsequent to, one or more other desired therapeutics or medical procedures (e.g., peptide vaccine can be used in combination therapy with another treatment such as chemotherapy, radiation, pharmaceutical agents, and/or another treatment). The particular combination of therapies (therapeutics or procedures) to employ in a combination regimen will take into account compatibility of the desired therapeutics and/or procedures and the desired therapeutic effect to be achieved. It will also be appreciated that the therapies employed may achieve a desired effect for the same disorder (for example, the compound of the present invention may be administered concurrently with another therapeutic or prophylactic).
[2840] The invention also provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the compositions of the invention. Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration.
[2841] The current invention provides for dosage forms comprising nucleic acid sequences or peptides suitable for treating cancer or other diseases. The dosage forms can be formulated, e.g., as sprays, aerosols, nanoparticles, liposomes, or other forms known to one of skill in the art. See, e.g., Remington’s Pharmaceutical Sciences; Remington: The Science and Practice of Pharmacy supra; Pharmaceutical Dosage Forms and Drug Delivery Systems by Howard C., Ansel et al., Lippincott Williams & Wilkins; 7th edition (Oct. 1, 1999).
[2842] Generally, a dosage form used in the acute treatment of a disease may contain larger amounts of one or more of the active ingredients it comprises than a dosage form used in the chronic treatment of the same disease. In addition, the prophylactically and therapeutically effective dosage form may vary among different conditions. For example, a therapeutically effective dosage form may contain peptides that has an appropriate immunogenic action when intending to treat cancer or other disease. On the other hand, a different effective dosage may contain nucleic acid sequences or peptides that has an appropriate immunogenic action when intending to use the peptides of the invention as a prophylactic (e.g., vaccine) against cancer or another disease/condition. These and other ways in which specific dosage forms encompassed by this invention will vary from one another and will be readily apparent to those skilled in the art. See, e.g, Remington’s Pharmaceutical Sciences, 2005, Mack Publishing Co.; Remington: The Science and Practice of Pharmacy by Gennaro, Lippincott Williams & Wilkins; 20th edition
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(2003); Pharmaceutical Dosage Forms and Drug Delivery Systems by Howard C. Ansel et al., Lippincott Williams & Wilkins; 7th edition (Oct. 1, 1999); and Encyclopedia of Pharmaceutical Technology, edited by Swarbrick, J. & J.C. Boylan, Marcel Dekker, Inc., New York, 1988, which are incorporated herein by reference in their entirety.
[2843] The pH of a composition or dosage form may also be adjusted to improve delivery' and/or stability of one or more active ingredients. Similarly, the polarity of a solvent carrier, its ionic strength, or tonicity can be adjusted to improve delivery. Compounds such as stearates can also be added to compositions or dosage forms to alter advantageously the hydrophilicity or lipophilicity of one or more active ingredients to improve delivery. In this regard, stearates can also serve as a lipid vehicle for the formulation, as an emulsify ing agent or surfactant, and as a delivery enhancing or penetration-enhancing agent. Different salts, hydrates, or solvates of the active ingredients can be used to adjust further the properties of the resulting composition.
[2844] Compositions can be formulated with appropriate carriers and adjuvants using techniques to yield compositions suitable for immunization. The compositions can include an adjuvant, such as, for example but not limited to, alum, poly IC, MF-59, squalene-based adjuvants, or liposomal based adjuvants suitable for immunization.
[2845] In some embodiments, the compositions and methods comprise any suitable agent or immune modulation which could modulate mechanisms of host immune tolerance and release of the induced antibodies. In certain embodiments, an immunomodulatory agent is administered in at time and in an amount sufficient for transient modulation of the subject's immune response so as to induce an immune response which comprises antibodies against, for example, tumor neoantigens (i.e., tumor-specific antigens (TSA)).
Expression systems
[2846] In certain aspects, the invention provides culturing a cell line that expresses any one of the peptides of the invention in a culture medium comprising any of the peptides described herein.
[2847] Various expression systems for producing recombinant proteins/peptides are known in the art, and include, prokaryotic (e.g., bacteria), plant, insect, yeast, and mammalian expression systems. Suitable cell lines, can be transformed, transduced, or transfected with nucleic acids containing coding sequences for the peptides of the invention in order to produce the molecule of interest. Expression vectors containing such a nucleic acid sequence, which can
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be linked to at least one regulatory sequence in a manner that allows expression of the nucleotide sequence in a host cell, can be introduced via methods known in the art. Practitioners in the art understand that designing an expression vector can depend on factors, such as the choice of host cell to be transfected and/or the type and/or amount of desired protein to be expressed.
Enhancer regions, which are those sequences found upstream or downstream of the promoter region in non-coding DNA regions, are also known in the art to be important in optimizing expression. If needed, origins of replication from viral sources can be employed, such as if a prokaryotic host is utilized for introduction of plasmid DNA. However, in eukaryotic organisms, chromosome integration is a common mechanism for DNA replication. For stable transfection of mammalian cells, a small fraction of cells can integrate introduced DNA into their genomes. The expression vector and transfection method utilized can be factors that contribute to a successful integration event. For stable amplification and expression of a desired protein, a vector containing DNA encoding a protein of interest is stably integrated into the genome of eukaryotic cells (for example, mammalian cells), resulting in the stable expression of transfected genes. A gene that encodes a selectable marker (for example, resistance to antibiotics or drugs) can be introduced into host cells along with the gene of interest in order to identify and select clones that stably express a gene encoding a protein of interest. Cells containing the gene of interest can be identified by drug selection wherein cells that have incorporated the selectable marker gene will survive in the presence of the drug. Cells that have not incorporated the gene for the selectable marker die. Surviving cells can then be screened for the production of the desired protein molecule.
[2848] A host cell strain, which modulates the expression of the inserted sequences, or modifies and processes the nucleic acid in a specific fashion desired also may be chosen. Such modifications (for example, glycosylation and other post-translational modifications) and processing (for example, cleavage) of peptide/protein products may be important for the function of the peptide/protein. Different host cell strains have characteristic and specific mechanisms for the post-translational processing and modification of proteins and gene products. As such, appropriate host systems or cell lines can be chosen to ensure the correct modification and processing of the target protein expressed. Thus, eukaryotic host cells possessing the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used.
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[2849] Various culturing parameters can be used with respect to the host cell being cultured. Appropriate culture conditions for mammalian cells are well known in the art (Cleveland WL, et al., J Immunol Methods, 1983, 56(2): 221-234) or can be determined by the skilled artisan (see, for example, Animal Cell Culture: A Practical Approach 2nd Ed., Rickwood, D. and Hames, B. D., eds. (Oxford University Press: New York, 1992)). Cell culturing conditions can vary according to the type of host cell selected. Commercially available medium can be utilized.
[2850] Peptides of the invention can be purified from any human or non-human cell which expresses the peptide, including those which have been transfected with expression constructs that express peptides of the invention. For protein recovery, isolation and/or purification, the cell culture medium or cell lysate is centrifuged to remove particulate cells and cell debris. The desired peptide molecule is isolated or purified away from contaminating soluble proteins and peptides by suitable purification techniques. Non-limiting purification methods for proteins include: size exclusion chromatography; affinity chromatography; ion exchange chromatography; ethanol precipitation; reverse phase HPLC; chromatography on a resin, such as silica, or cation exchange resin, e.g., DEAE; chromatofocusing; SDS-PAGE; ammonium sulfate precipitation; gel filtration using, e.g., Sephadex G-75, Sepharose; protein A sepharose chromatography for removal of immunoglobulin contaminants; and the like. Other additives, such as protease inhibitors e.g., PMSF or proteinase K) can be used to inhibit proteolytic degradation during purification. Purification procedures that can select for carbohydrates can also be used, e.g., ion-exchange soft gel chromatography, or HPLC using cation- or anionexchange resins, in which the more acidic fraction(s) is/are collected.
Methods of treatment
[2851] In one embodiment, the subject matter disclosed herein relates to a preventive medical treatment started after following diagnosis of cancer in order to prevent the disease from worsening or curing the disease. In one embodiment, the subject matter disclosed herein relates to prophylaxis of subjects who are believed to be at risk for cancer or have previously been diagnosed with cancer (or another disease). In one embodiment, said subjects can be administered a composition of the invention. The invention contemplates using any of the nucleic acid sequences or peptides produced by the systems and methods described herein. In one embodiment, the compositions described herein can be administered subcutaneously via syringe or any other suitable method known in the art.
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[2852] The compound(s) or combination of compounds disclosed herein, or pharmaceutical compositions may be administered to a cell, mammal, or human by any suitable means. Nonlimiting examples of methods of administration include, among others, (a) administration though oral pathways, which includes administration in capsule, tablet, granule, spray, syrup, or other such forms; (b) administration through non-oral pathways such as intraocular, intranasal, intraauricular, rectal, vaginal, intraurethral, transmucosal, buccal, or transdermal, which includes administration as an aqueous suspension, an oily preparation or the like or as a drip, spray, suppository, salve, ointment or the like; (c) administration via injection, including subcutaneously, intraperitoneally, intravenously, intramuscularly, intradermally, intraorbitally, intracapsularly, intraspinally, intrastemally, or the like, including infusion pump delivery;
(d) administration locally such as by injection directly in the renal or cardiac area, e.g., by depot implantation; (e) administration topically; as deemed appropriate by those of skill in the art for bringing the compound or combination of compounds disclosed herein into contact with living tissue; (f) administration via inhalation, including through aerosolized, nebulized, and powdered formulations; and (g) administration through implantation.
[2853] As will be readily apparent to one skilled in the art, the effective in vivo dose to be administered and the particular mode of administration will vary depending upon the age, weight and species treated, and the specific use for which the compound or combination of compounds disclosed herein are employed. The determination of effective dose levels, that is the dose levels necessary to achieve the desired result, can be accomplished by one skilled in the art using routine pharmacological methods. Typically, human clinical applications of products are commenced at lower dose levels, with dose level being increased until the desired effect is achieved. Alternatively, acceptable in vitro studies can be used to establish useful doses and routes of administration of the compositions identified by the present methods using established pharmacological methods. Effective animal doses from in vivo studies can be converted to appropriate human doses using conversion methods known in the art (e.g., see Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. Journal of Basic and Clinical Pharmacy. 2016 Mar;7(2):27.)
Methods of prevention
[2854] In some embodiments, the peptides prepared using methods of the invention can be used as a vaccine to promote an immune response against cancer (e.g., against tumor neoantigens). In some embodiments, the invention provides compositions and methods for
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induction of immune response, for example, induction of antibodies to tumor neoantigens. In some embodiments, the antibodies are broadly neutralizing antibodies. In some embodiments, the invention provides compositions and methods for induction of immune response, for example, induction of a T cell response to neoantigens. In some embodiments, the compositions prepared using methods of the invention can be used as a vaccine to promote an immune response against a pathogen. In some embodiments, the nucleic acid sequences or peptides prepared using methods of the invention can be used to promote immune tolerance as an autoimmune disease therapeutic.
[2855] In some embodiments, the peptides prepared using methods disclosed herein can be combined with additional therapeutic components. In some embodiments, the combination can be encoded in one or more nucleic acids that encode the peptides produced with the methods described herein and additional therapeutic components (e.g, peptides or proteins) that are known in the art. In some embodiments, the combination is created by adding one or more nucleic acids that encode the additional therapeutic components of the peptides that result from the methods described herein for combined formulation and packaging. In some embodiments, additional therapeutic components are encoded on the same nucleic acid molecules that encode the sequences described herein. An example of the combination of components is the creation of vaccines that contain components of tumor cell-associated proteins, such as MICA or MICB (Badrinath et al., 2022). In some embodiments, peptide components to invoke an adaptative immune response can be added to such combined vaccines (e.g., MICA or MICB) by using one or more nucleic acids to encode the components and packaging the nucleic acids in an LNP to form an RNA-LNP (e.g, mRNA-LNP) or DNA-LNP formulation, or separately formulating different components as RNA-LNP (e.g, mRNA-LNP) or DNA-LNP and then combining them for packaging or immediately before administration to a person. In some embodiments, cancer or other vaccines that contain nucleic acids encoding one or more protein fragments to produce an antibody response can be combined with a peptide vaccine using the methods described herein to produce a cellular immune response.
[2856] The compositions, systems, and methods disclosed herein are not to be limited in scope to the specific embodiments described herein. Indeed, various modifications of the compositions, systems, and methods in addition to those described will become apparent to those of skill in the art from the foregoing description.
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660
SUBSTITUTE SHEET (RULE 26)
Claims
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 What is claimed is: 1. A composition comprising one or more polynucleotides encoding at least two amino acid sequences, wherein the at least two amino acid sequences are selected from the group consisting of SEQ ID NOs: 17 to 176, and SEQ ID NOs: 178 to 184. 2. The composition of claim 1, wherein the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides. 3. The composition of claim 2, wherein an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. 4. The composition of claim 3, wherein the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. 5. The composition of claim 1, wherein each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a CTNNB1 protein. 6. The composition of claim 5, wherein the fragment of the CTNNB1 protein comprises a mutation selected from the group consisting of CTNNB1 D32G, CTNNB1 G34E, CTNNB1 S33C, CTNNB1 S33F, CTNNB1 S37C, CTNNB1 S37F, CTNNB1 S45F, CTNNB1 S45P, CTNNB1 T41A, and CTNNB1 T41I. 7. A method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the composition of claim 1, wherein the composition is an immunogenic composition. - 594 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 8. The composition of claim 1, wherein the at least two amino acid sequences are SEQ ID NOs: 103 and 104. 9. A composition comprising one or more polynucleotides encoding at least two amino acid sequences selected from the group consisting of SEQ ID NOs: 185 to 207 and SEQ ID NOs: 209 to 222. 10. The composition of claim 9, wherein the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides. 11. The composition of claim 10, wherein an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. 12. The composition of claim 11, wherein the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. 13. The composition of claim 9, wherein each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a KRAS protein. 14. The composition of claim 13, wherein the fragment of the KRAS protein comprises a mutation selected from the group consisting of KRAS A146T, KRAS A146V, and KRAS Q61H. 15. A method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the composition of claim 9, wherein the composition is an immunogenic composition. - 595 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 16. The composition of claim 9, wherein the at least two amino acid sequences are SEQ ID NOs: 203 and 204. 17. A composition comprising one or more polynucleotides encoding at least two amino acid sequences, wherein the at least two amino acid sequences are selected from the group consisting of SEQ ID NOs: 223 to 240, SEQ ID NOs: 243 to 293, SEQ ID NOs: 295 to 315, SEQ ID NOs: 317 to 329, SEQ ID NOs: 331 to 339, and SEQ ID NOs: 341 to 386. 18. The composition of claim 17, wherein the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides. 19. The composition of claim 18, wherein an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. 20. The composition of claim 19, wherein the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. 21. The composition of claim 17, wherein each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a PIK3CA protein. 22. The composition of claim 21, wherein the fragment of the PIK3CA protein comprises a mutation selected from the group consisting of PIK3CA C420R, PIK3CA E453K, PIK3CA E545A, PIK3CA E726K, PIK3CA G118D, PIK3CA H1047L, PIK3CA N345K, PIK3CA Q546K, PIK3CA Q546R, and PIK3CA R108H. - 596 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 23. A method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the composition of claim 17, wherein the composition is an immunogenic composition. 24. The composition of claim 17, wherein the at least two amino acid sequences are SEQ ID NOs: 308 and 309. 25. A composition comprising one or more polynucleotides encoding at least two amino acid sequences, wherein the at least two amino acid sequences are selected from the group consisting of SEQ ID NOs: 387 to 445, SEQ ID NOs: 447 to 472, SEQ ID NOs: 474 to 480, SEQ ID NOs: 482 to 500, SEQ ID NOs: 502 to 544, SEQ ID NOs: 546 to 550, SEQ ID NOs: 552 to 564, SEQ ID NOs: 566 to 582, SEQ ID NO: 584, SEQ ID NOs: 586 to 605, SEQ ID NOs: 607 to 633, SEQ ID NOs: 638 to 656, SEQ ID NOs: 659 to 664, and SEQ ID NOs: 666 to 794. 26. The composition of claim 25, wherein the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides. 27. The composition of claim 26, wherein an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject. 28. The composition of claim 27, wherein the administration of the one or more polynucleotides causes: a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles, wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele. 29. The composition of claim 25, wherein each of the at least two amino acid sequences comprises a heteroclitic modification of a fragment of a TP53 protein. - 597 - ActiveUS 205953775
Attorney Docket No. 2215269.00133WO1 Date of Electronic Deposit: September 16, 2024 30. The composition of claim 29, wherein the fragment of the TP53 protein comprises a mutation selected from the group consisting of TP53 C176F, TP53 C176Y, TP53 C238Y, TP53 C275Y, TP53 E285K, TP53 G245S, TP53 G245V, TP53 H179Y, TP53 H193R, TP53 I195T, TP53 K132E, TP53 K132N, TP53 P151S, TP53 R213L, TP53 R249M, TP53 R249S, TP53 R273L, TP53 R280K, TP53 S127Y, TP53 S241F, TP53 V157F, TP53 V272M, TP53 Y163C, TP53 Y205C, and TP53 Y234C. 31. A method of preventing or treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the composition of claim 25, wherein the composition is an immunogenic composition. 32. The composition of claim 25, wherein the at least two amino acid sequences are SEQ ID NOs: 474 and 475. - 598 - ActiveUS 205953775
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20180153975A1 (en) * | 2015-05-20 | 2018-06-07 | The Broad Institute Inc. | Shared neoantigens |
| WO2021207152A1 (en) * | 2020-04-06 | 2021-10-14 | Vanderbilt University | Cross-reactive coronavirus antibodies and uses thereof |
| US20220370584A1 (en) * | 2021-04-28 | 2022-11-24 | Think Therapeutics, Inc. | Compositions and method for optimized peptide vaccines using residue optimization |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20180153975A1 (en) * | 2015-05-20 | 2018-06-07 | The Broad Institute Inc. | Shared neoantigens |
| WO2021207152A1 (en) * | 2020-04-06 | 2021-10-14 | Vanderbilt University | Cross-reactive coronavirus antibodies and uses thereof |
| US20220370584A1 (en) * | 2021-04-28 | 2022-11-24 | Think Therapeutics, Inc. | Compositions and method for optimized peptide vaccines using residue optimization |
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