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WO2025227066A2 - Ras vaccine compositions and methods of use - Google Patents

Ras vaccine compositions and methods of use

Info

Publication number
WO2025227066A2
WO2025227066A2 PCT/US2025/026433 US2025026433W WO2025227066A2 WO 2025227066 A2 WO2025227066 A2 WO 2025227066A2 US 2025026433 W US2025026433 W US 2025026433W WO 2025227066 A2 WO2025227066 A2 WO 2025227066A2
Authority
WO
WIPO (PCT)
Prior art keywords
sequence
hla
seq
ras
nucleic acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/026433
Other languages
French (fr)
Other versions
WO2025227066A3 (en
Inventor
Kendra FOLEY
Vikram JUNEJA
Shirisha MEDA
Christina M. ARIETA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biontech US Inc
Original Assignee
Biontech US Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biontech US Inc filed Critical Biontech US Inc
Publication of WO2025227066A2 publication Critical patent/WO2025227066A2/en
Publication of WO2025227066A3 publication Critical patent/WO2025227066A3/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • 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
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/53—DNA (RNA) vaccination
    • 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
    • A61K2039/70—Multivalent vaccine

Definitions

  • a method of treating a subject with a disease or condition comprising administering to the subject a therapy comprising (i) a multiepitopic polypeptide, (ii) a recombinant nucleic acid encoding the multiepitopic polypeptide, or (iii) a cell comprising the multiepitopic polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length RAS polypeptide and comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, wherein the first RAS epitope sequence and the second RAS epitope sequence are different, and wherein presentation of the first and/or second RAS epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered
  • APCs antigen presenting cells
  • Also provided herein is a method of treating a subject with a disease or condition comprising administering to the subject a therapy comprising (i) a multiepitopic polypeptide, (ii) a recombinant nucleic acid encoding the multiepitopic polypeptide, or (iii) a cell comprising the multiepitopic polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length RAS polypeptide and comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, wherein the first RAS epitope sequence and the second RAS epitope sequence are different, and wherein the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker.
  • the full-length RAS polypeptide is a full-length KRAS, NRAS or HRAS polypeptide, wherein the first RAS amino acid sequence is a first KRAS, NRAS or HRAS WSGR Docket No.50401-795.601 amino acid sequence, and wherein the second RAS amino acid sequence is a second KRAS, NRAS or HRAS amino acid sequence.
  • the method of any one of the preceding embodiments further comprises administering the subject a T-cell receptor (TCR), a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR.
  • TCR T-cell receptor
  • the first RAS epitope sequence and the second RAS epitope sequence is separated by a linker.
  • the first RAS amino acid sequence is the first epitope sequence and/or the second RAS amino acid sequence is the second epitope sequence.
  • the first RAS amino acid sequence comprises a first RAS mutation
  • the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation.
  • the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C.
  • the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C.
  • the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell.
  • the first RAS mutation is G12V, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 58-62 and 65-72.
  • the first RAS mutation is G12D, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79.
  • the first RAS mutation is G12C, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096.
  • the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length RAS polypeptide.
  • the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length RAS polypeptide.
  • the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker.
  • the first RAS amino acid sequence comprises the first RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first RAS epitope sequence from the full-length RAS polypeptide.
  • the second RAS amino acid sequence comprises the second RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide.
  • the multiepitopic polypeptide does not comprise more than 12 or more consecutive amino acids from the full-length RAS polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length RAS polypeptide.
  • the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the first or the second RAS epitope sequence, and (ii) a human MHC encoded by an HLA allele.
  • the multiepitopic polypeptide is a RAS polypeptide comprising the first RAS epitope sequence and the second RAS epitope sequence.
  • the linker is a cleavable linker.
  • a method of treating a subject with a disease or condition comprising administering to the subject (a) a RAS polypeptide, (b) a recombinant nucleic acid encoding the RAS polypeptide, or (c) a cell comprising the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide, wherein the RAS polypeptide comprises a RAS epitope sequence, wherein the subject has been previously administered a T-cell receptor (TCR), a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS epitope sequence, and (ii) a T-cell receptor (TCR), a recombinant
  • Also provided herein is a method of treating a subject with a disease or condition comprising administering to the subject a T-cell receptor (TCR), a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) a RAS epitope sequence, and (ii) a human MHC encoded by an HLA allele, wherein the subject has been previously administered (a) a RAS polypeptide, (b) a recombinant nucleic acid encoding the RAS polypeptide, or (c) a cell comprising the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide, wherein the RAS polypeptide comprises the RAS epitope sequence.
  • TCR T-cell receptor
  • Also provided herein is a method of treating a subject with a disease or condition comprising, administering to the subject (i) a RAS polypeptide, (ii) a recombinant nucleic acid encoding the RAS polypeptide, or (iii) a cell comprising the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide, wherein the RAS polypeptide comprises a RAS epitope sequence; and administering to the subject a TCR, a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes WSGR Docket No.50401-795.601 and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS peptide sequence, and (ii) a human MHC encoded by an HLA allele.
  • administering in (a) is performed concurrently with administering in (b). [0029] In some embodiments, administering in (a) is prior to administering in (b). [0030] In some embodiments, administering in (a) is subsequent to administering in (b). [0031] In some embodiments, the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years or more after the subject has been administered the TCR or the recombinant nucleic acid encoding the TCR.
  • the TCR or the recombinant nucleic acid encoding the TCR is administered at least 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years or more after the subject has been administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide.
  • the cell is an immune cell.
  • the T-cell receptor (TCR) or the recombinant nucleic acid encoding the TCR is expressed by an immune cell.
  • the TCR is a soluble TCR.
  • the method of any one of the preceding embodiments further comprises administering two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs, or cells comprising the two or more different TCRs or the recombinant nucleic acids encoding the two or more different TCRs and wherein the two or more different TCRs comprise a first TCR and a second TCR.
  • the two or more different TCRs are expressed on surface of two different immune cells.
  • the first TCR and the second TCR bind to different peptide:MHC complexes, each peptide:MHC complex comprising (i) an epitope sequence and (ii) a human MHC encoded by an HLA allele.
  • the two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs are administered separately or co-administered in a same mixture.
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12V mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA- C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05
  • the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12D WSGR Docket No.50401-795.601 mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA- B*07:02, HLA-C*08:02, HLA-C*03:04, HLA
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12V mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA- C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05
  • the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12C mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA- DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12D mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA- A*11:01, and HLA-A*68:01.
  • the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12C mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA- C*03:03.
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 58-62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75- 79 and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, H
  • the RAS polypeptide does not comprise a full-length RAS protein sequence.
  • the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 59.
  • the HLA allele is selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*03:02, HLA-A*03:05, HLA-B*40:01, and HLA-A*68:01.
  • the RAS epitope sequence comprises a sequence of SEQ ID NO: 60.
  • the HLA allele is HLA-C*01:02.
  • the RAS epitope sequence comprises a sequence of SEQ ID NOs: 61 or 62.
  • the HLA allele is HLA-C*03:03, or HLA-C*03:04.
  • the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 59.
  • the MHC allele is HLA-A*11:01.
  • the RAS epitope sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 65-71.
  • the MHC allele is HLA-DRB1*07:01.
  • the RAS epitope sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 58 or 72.
  • the MHC allele is selected from the group consisting of HLA- A*03:01, HLA-A*03:02, and HLA-A*03:05.
  • the RAS epitope sequence comprises a sequence of SEQ ID NO: 75.
  • the MHC allele is selected from the group consisting of HLA- B*07:02, HLA-C*08:02, HLA-C*03:04, and HLA-C*05:01.
  • the RAS epitope sequence comprises a sequence of SEQ ID NO: 76.
  • the MHC allele is selected from the group consisting of HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01.
  • the RAS epitope sequence comprises a sequence of SEQ ID NO: 77.
  • the MHC allele is HLA-A*11:01.
  • the RAS epitope sequence comprises a sequence of SEQ ID NOs: 78 or 79.
  • the MHC allele is HLA-C*08:02.
  • the RAS epitope sequence comprises a sequence of SEQ ID NO: 29.
  • the MHC allele is HLA-DRB1*11:01.
  • the RAS epitope sequence comprises a sequence of SEQ ID NO: 81 or 1096.
  • the MHC allele is selected from the group consisting of HLA-A*3:01, HLA-A*11:01, and HLA-A*68:01.
  • the RAS epitope sequence comprises a sequence of SEQ ID NO: 82.
  • the MHC allele is HLA-C*03:03.
  • the RAS polypeptide is a multiepitopic polypeptide, and wherein the multiepitopic polypeptide does not comprise a full-length RAS polypeptide and comprises two or more different RAS epitope sequences.
  • the multiepitopic polypeptide comprises at least 3, 4, 5, or more different RAS epitope sequences.
  • the two or more different RAS epitope sequences are separated by linker sequences.
  • antigen presenting cells (APCs) of the subject administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide comprising the multiepitopic polypeptide present more of a RAS epitope sequence as a peptide:MHC complex compared to the APCs of a subject administered a full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide.
  • T cells of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide exhibit increased expansion compared to T cells of a subject administered a full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide.
  • the multiepitopic polypeptide comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, and wherein the first RAS epitope sequence and the second RAS epitope sequence are different or wherein the first RAS amino acid sequence and the second RAS amino acid sequence comprise different RAS mutations.
  • the first RAS epitope sequence and the second RAS epitope sequence is separated by a linker.
  • WSGR Docket No.50401-795.601 [0078]
  • the first amino acid sequence is the first epitope sequence and/or the second amino acid sequence is the second epitope sequence.
  • the first amino acid sequence consists of the first epitope sequence, and/or the second amino acid sequence consists of the second epitope sequence.
  • the first RAS amino acid sequence comprises a first RAS mutation
  • the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation.
  • the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C.
  • the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C.
  • the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell.
  • the first RAS mutation is G12V, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72.
  • the first RAS mutation is G12D, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79.
  • the first RAS mutation is G12C, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096.
  • the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length RAS polypeptide.
  • the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length RAS polypeptide.
  • the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker.
  • the first amino acid sequence comprises the first RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first RAS epitope sequence from the full-length RAS polypeptide.
  • the second amino acid sequence comprises the second RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide.
  • the multiepitopic polypeptide does not comprise more than 12 or more consecutive amino acids from the full-length RAS polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length RAS polypeptide.
  • WSGR Docket No.50401-795.601 the first RAS epitope sequence and the second RAS epitope sequence are presentable by different HLA alleles, are presented by different HLA alleles, bind to different HLA alleles, are predicted to bind to different HLA alleles, or are predicted to be presented by different HLA alleles.
  • a first RAS epitope sequence (i) binds to or is predicted to bind to a first HLA allele with a KD of less than 100 nM and (ii) to binds to or is predicted to bind to a second HLA allele with a KD of more than 500 nM.
  • the first amino acid sequence is operably linked to the second amino acid sequence via a linker.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the multiepitopic polypeptide comprises a first amino acid sequence comprising a first RAS epitope sequence, operably linked to a second amino acid sequence comprising a second RAS epitope sequence, operably linked to a third amino acid sequence comprising a third RAS epitope sequence.
  • the first RAS epitope sequence, the second RAS epitope sequence, and/or the third RAS epitope sequence comprises a RAS mutation selected from the group consisting of G12V, G12D, and G12C, and wherein the first RAS epitope sequence, the second RAS epitope sequence, and the third RAS epitope sequence comprise different RAS mutations.
  • the first RAS epitope sequence comprises a G12V mutation.
  • the second RAS epitope sequence comprises a G12D mutation.
  • the third RAS epitope sequence comprises a G12C mutation.
  • the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-
  • the subject does not express an HLA allele that recognizes each RAS epitope sequence of the multiepitopic polypeptide.
  • the subject only expresses HLA alleles that recognize a subset of RAS epitope sequences of the multiepitopic polypeptide.
  • the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0108] In some embodiments, the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 27-29. WSGR Docket No.50401-795.601 [0109] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 27, operably linked to a sequence of SEQ ID NO: 29, and operably linked to a sequence of SEQ ID NO: 28.
  • the sequence of SEQ ID NO: 27 is operably linked to the sequence of SEQ ID NOs: 29 via a linker, and the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NOs: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27.
  • the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 28, operably linked to a sequence of SEQ ID NO: 27, and operably linked to a sequence of SEQ ID NO: 29.
  • the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker
  • the sequence of SEQ ID NO: 27 is operably linked to a sequence of SEQ ID NO: 29 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 27, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 29.
  • the sequence of SEQ ID NO: 27 is operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 is operably linked to a sequence of SEQ ID NO: 29 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 28, operably linked to a sequence of SEQ ID NO: 29, and operably linked to a sequence of SEQ ID NO: 27.
  • the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 29 via a linker
  • the sequence of SEQ ID NO: 29 is operably linked to a sequence of SEQ ID NO: 27 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 27, and operably linked to a sequence of SEQ ID NO: 28.
  • the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 27 via a linker
  • the sequence of SEQ ID NO: 27 is operably linked to a sequence of SEQ ID NO: 28 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the RAS polypeptide comprises at least two copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises three copies of the multiepitopic polypeptide.
  • the RAS polypeptide comprises five copies of the multiepitopic polypeptide.
  • the RAS polypeptide further comprises a secretory domain (Sec) sequence at the N terminus of the multiepitopic polypeptide.
  • the Sec sequence comprises a sequence of SEQ ID NO: 32.
  • the Sec sequence is operably linked to the multiepitopic polypeptide via a linker.
  • the linker comprises a sequence of SEQ ID NO: 30 or 112.
  • the RAS polypeptide further comprises an MHC class I trafficking domain (MITD) sequence at the C terminus of the multiepitopic polypeptide.
  • the MITD sequence comprises a sequence of SEQ ID NO: 33.
  • the multiepitopic polypeptide is operably linked to the MITD sequence via a linker.
  • the linker comprises a sequence of SEQ ID NO: 30 or 112.
  • WSGR Docket No.50401-795.601 [0144]
  • the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 25.
  • the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 26.
  • the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 113.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. [0148] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14- 23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 14- 16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109.
  • the sequence selected from the group consisting of SEQ ID NOs: 14- 16, 84, 92, 96, 100, 104, and 108 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 via a linker sequence
  • the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence.
  • the linker sequence encodes a cleavable linker.
  • the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20- 23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of WSGR Docket No.50401-795.601 SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108.
  • the sequence selected from the group consisting of SEQ ID NOs: 20- 23, 88, 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence
  • the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 via a linker sequence.
  • the linker sequence encodes a cleavable linker.
  • the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110.
  • the sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 via a linker sequence
  • the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 is operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 via a linker sequence.
  • the linker sequence is a cleavable linker.
  • the linker sequence comprises a sequence of selected from the group consisting of SEQ ID NOs: 5, 6, 8-13.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises at least two copies of a string of sequences, and wherein each string of sequences comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of the string of sequences. [0165] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of the string of sequences. WSGR Docket No.50401-795.601 [0166] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a secretory (Sec) sequence at the 5’end of the string of sequences. [0167] In some embodiments, the sequence encoding the Sec sequence comprises a sequence of SEQ ID NO: 3.
  • the sequence encoding the Sec sequence is operably linked to the string of sequences via a linker sequence.
  • the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89.
  • the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MITD sequence at the 3’ end of the string of sequences.
  • the sequence encoding the MITD domain comprises a sequence of SEQ ID NO: 24 or 90.
  • the string of sequences is operably linked to the sequence encoding the MITD sequence via a linker sequence.
  • the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89.
  • the recombinant nucleic acid is codon-optimized.
  • the recombinant nucleic acid is an RNA.
  • the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 91, 95, 99, 103, 107, 111.
  • the subject expresses more of the RAS epitope when administered with the codon-optimized recombinant nucleic acid than administered with wild-type recombinant nucleic acid.
  • the TCR comprises a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR beta chain construct comprises a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO: 57.
  • the TCR beta chain construct comprises a variable region having an amino acid sequence with at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 52 or SEQ ID NO: 53.
  • the TCR beta chain construct comprises a complementarity determining region 1 (CDR1) having an amino acid sequence set forth in SEQ ID NO: 55 and a complementarity determining region 2 (CDR2) having an amino acid sequence set forth in SEQ ID NO: 56.
  • CDR1 complementarity determining region 1
  • CDR2 complementarity determining region 2
  • the TCR alpha chain construct comprises a CDR1, a CDR2, and a CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 46, the CDR2 has an amino acid sequence set forth in SEQ ID NO: 47, and the CDR3 has an amino acid sequence set forth in SEQ ID NO: 48.
  • the TCR alpha chain construct comprises a variable region having an amino acid sequence having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44.
  • the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NO: 49 or SEQ ID NO: 51, or an amino acid sequence that is at least 80% identical to SEQ ID NO: 49 or SEQ ID NO: 51, and (b) an alpha chain having an amino acid sequence set forth in SEQ ID NO: 40 or SEQ ID NO: 42, or an amino acid sequence that is at least 80% identical to SEQ ID NO: 40 or SEQ ID NO: 42.
  • the TCR is selected from the TCRs presented in Tables 8A-8D. [0185] In some embodiments, binding of the TCR to the peptide:MHC complex results in production of a cytokine by the immune cell. [0186] In some embodiments, the cytokine is IFN- ⁇ , TNF- ⁇ , IL-2, IL-18, or any combination thereof.
  • a recombinant nucleic acid encoding a RAS polypeptide comprising a multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length RAS polypeptide and comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, wherein the first RAS epitope sequence and the second RAS epitope sequence are different, and wherein the first RAS amino acid sequence and the second RAS amino acid sequence are linked via a linker.
  • presentation of the first and/or second RAS epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide is higher than the presentation of the first and/or second RAS epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide.
  • the first RAS amino acid sequence is the first epitope sequence and/or the second RAS amino acid sequence is the second epitope sequence.
  • the first RAS amino acid sequence consists of the first epitope sequence, and/or the second RAS amino acid sequence consists of the second epitope sequence.
  • the first RAS amino acid sequence comprises a first RAS mutation
  • the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation.
  • WSGR Docket No.50401-795.601 [0192]
  • the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C.
  • the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C.
  • the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell.
  • the first RAS mutation is G12V, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72.
  • the first RAS mutation is G12D, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79.
  • the first RAS mutation is G12C, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096.
  • the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length RAS polypeptide.
  • the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length RAS polypeptide.
  • the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker.
  • the first RAS amino acid sequence comprises the first RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first RAS epitope sequence from the full-length RAS polypeptide.
  • the second RAS amino acid sequence comprises the second RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide.
  • the multiepitopic polypeptide does not comprise more than 12 or more consecutive amino acids from the full-length RAS polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length RAS polypeptide.
  • the RAS polypeptide further comprises a Secretory (Sec) sequence at the N terminus of the multiepitopic polypeptide.
  • the Sec sequence comprises a sequence of SEQ ID NO: 32.
  • the Sec sequence is operably linked to the multiepitopic polypeptide via a linker.
  • the linker comprises a sequence of SEQ ID NO: 30 or 112.
  • the RAS polypeptide further comprises an MHC class I trafficking signal (MITD) sequence at the C terminus of the multiepitopic polypeptide.
  • MITD MHC class I trafficking signal
  • the MITD sequence comprises a sequence of SEQ ID NO: 33.
  • the multiepitopic polypeptide is operably linked to the MITD sequence via a linker.
  • the linker comprises a sequence of SEQ ID NO: 30 or 112.
  • the multiepitopic polypeptide comprises at least 3, 4, 5, or more different RAS epitope sequences.
  • the first RAS epitope sequence and the second RAS epitope sequence are presentable by different HLA alleles, are presented by different HLA alleles, bind to different HLA alleles, are predicted to bind to different HLA alleles, or are predicted to be presented by different HLA alleles.
  • the first RAS epitope sequence (i) binds to or is predicted to bind to a first HLA allele with a KD of less than 100 nM and (ii) to binds to or is predicted to bind to a second HLA allele with a KD of more than 500 nM.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the multiepitopic polypeptide comprises a first amino acid sequence comprising a first RAS epitope sequence, operably linked to a second amino acid sequence comprising a second RAS epitope sequence, operably linked to a third amino acid sequence comprising a third RAS epitope sequence.
  • the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-
  • the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2])x-CT seq, where x is an integer from 1 to 10.
  • the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2]-cleavable linker2-[Antigen3])x-CT seq, where x is an integer from 1 to 10.
  • the NT seq comprises a Secretory (Sec) sequence and a N-terminal linker sequence.
  • the CT seq comprises a C-terminal linker and a MITD sequence.
  • the Antigen1, Antigen2, or Antigen3 is comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 27-29.
  • the cleavable linker1 or cleavable linker2 is selected from the group consisting of SEQ ID NOs: 30 and 31.
  • the N-terminal linker sequence or the C-terminal linker sequence is selected from the group consisting of SEQ ID NOs: 30 and 31.
  • the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0226] In some embodiments, the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0227] In some embodiments, the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0228] In some embodiments, the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 27, operably linked to a sequence of SEQ ID NO: 29, and operably linked to a sequence of SEQ ID NO: 28.
  • the sequence of SEQ ID NO: 27 is operably linked to the sequence of SEQ ID NO: 29 via a linker
  • the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27.
  • the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker
  • the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 28, operably linked to a sequence of SEQ ID NO: 27, and operably linked to a sequence of SEQ ID NO: 29.
  • the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker
  • the sequence of SEQ ID NO: 27 is operably linked to a sequence of SEQ ID NO: 29 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the RAS polypeptide comprises at least two copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID WSGR Docket No.50401-795.601 NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises three copies of the multiepitopic polypeptide.
  • the RAS polypeptide comprises five copies of the multiepitopic polypeptide.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. [0245] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NO:s 14- 23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 14- 16, 84, 92, 96, 100, 104, and 108 , operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109.
  • sequence selected from the group consisting of SEQ ID NOs: 14- 16, 84, 92, 96, 100, 104, and 108 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 via a linker sequence
  • sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence.
  • the linker sequence encodes a cleavable linker.
  • the linker sequence comprises a sequence of selected from the group consisting of SEQ ID NOs: 5, 6, 8-13.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20- 23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of WSGR Docket No.50401-795.601 SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108.
  • the sequence selected from the group consisting of SEQ ID NOs: 20- 23, 88, 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence
  • the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 via a linker sequence.
  • the linker sequence encodes a cleavable linker.
  • the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110.
  • the sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 via a linker sequence
  • the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 is operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 via a linker sequence.
  • the linker sequence is a cleavable linker.
  • the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises at least two copies of a string of sequences, and wherein each string of sequences comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of the string of sequences. [0262] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of the string of sequences. WSGR Docket No.50401-795.601 [0263] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a Sec sequence at the 5’ end of the string of sequences. [0264] In some embodiments, the sequence encoding the Sec sequence comprises a sequence of SEQ ID NO: 3.
  • the sequence encoding the Sec sequence is operably linked to the string of sequences via a linker sequence.
  • the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89.
  • the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MITD sequence at the 3’ end of the string of sequences.
  • the sequence encoding the MITD sequence comprises a sequence of SEQ ID NO: 24 or 90.
  • the string of sequences is operably linked to the sequence encoding the MITD sequence via a linker sequence.
  • the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89.
  • a recombinant nucleic acid having at least 60% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 91, 95, 99, 103, 107, 111.
  • a recombinant nucleic acid having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 91, 95, 99, 103, 107, 111.
  • a polypeptide encoded by the recombinant nucleic acid of any one of the preceding embodiments is also provided herein.
  • a pharmaceutical composition comprising the recombinant nucleic acid of any one of the preceding embodiments or the polypeptide of any one of the preceding embodiments, and a pharmaceutically acceptable carrier.
  • nucleic acid of any one of the preceding embodiments polypeptide of any one of the preceding embodiments, or the pharmaceutical composition of any one of the preceding embodiments for use in therapy.
  • FIGs.1-2 depict an exemplary vaccine construct containing three different antigenic KRAS protein mutants.
  • FIG.1 is a cartoon depicting the protein domains and linkers encoded by the construct.
  • FIG.2 shows the fully annotated sequence of the exemplary construct.
  • FIGs.3A-3D depict results from a T cell activation experiment measuring IFN- ⁇ secretion by T cells incubated with monocyte-derived dendritic cells (moDCs) transfected with the construct shown in FIG.1, a construct containing three repeats of the antigenic KRAS mutants, an irrelevant construct, or with no moDCs.
  • FIG.3A depicts results using T cells expressing a TCR recognizing KRAS G12V mutant presented by HLA-DRB1:07:01, left and right panels are from different T cell donors.
  • FIG.3B depicts results using T cells expressing a TCR recognizing KRAS G12V mutant presented by HLA-A11:01, left and right panels are from different T cell donors.
  • FIG.3C depicts results using T cells expressing a TCR recognizing KRAS G12D mutant presented by HLA-A11:01, left and right panels are from different T cell donors.
  • FIG.3D depicts results using T cells expressing a TCR recognizing KRAS G12D mutant presented by HLA-C08:02, left and right panels are from different T cell donors.
  • FIG.4 depicts results from a T cell activation experiment measuring IFN- ⁇ secretion by T cells incubated with monocyte-derived dendritic cells (moDCs) transfected with the constructs described in Table 6. Left and right panels depict results obtained using two different T cell donors.
  • moDCs monocyte-derived dendritic cells
  • Neoantigens encompass, but are not limited to, tumor antigens which arise from, for example, a WSGR Docket No.50401-795.601 substitution in a protein sequence, a frame shift mutation, a fusion polypeptide, an in-frame deletion, an insertion, and expression of an endogenous retroviral polypeptide.
  • a “neoepitope” refers to an epitope that is not present in a reference, such as a non-diseased cell, e.g., a non-cancerous cell or a germline cell, but is found in a diseased cell, e.g., a cancer cell.
  • a “mutation” refers to a change of or a difference in a nucleic acid sequence (e.g., a nucleotide substitution, addition or deletion) compared to a reference nucleic acid.
  • a “somatic mutation” can occur in any of the cells of the body except the germ cells (sperm and egg) and are not passed on to children. These alterations can (but do not always) cause cancer or other diseases.
  • a mutation is a non-synonymous mutation.
  • a “non-synonymous mutation” refers to a mutation, for (e.g., a nucleotide substitution), which does result in an amino acid change such as an amino acid substitution in the translation product.
  • a “frameshift” occurs when a mutation disrupts the normal phase of a gene’s codon periodicity (also known as “reading frame”), resulting in translation of a non-native protein sequence. It is possible for different mutations in a gene to achieve the same altered reading frame.
  • Antigen processing refers to the degradation of a polypeptide or antigen into procession products, which are fragments of said polypeptide or antigen (e.g., the degradation of a polypeptide into peptides) and the association of one or more of these fragments (e.g., via binding) with MHC molecules for presentation by cells, for example, antigen presenting cells, to specific T cells.
  • An “antigen presenting cell” refers to a cell which presents peptide fragments of protein antigens in association with MHC molecules on its cell surface.
  • the term includes professional antigen presenting cells (e.g., B lymphocytes, monocytes, dendritic cells, Langerhans cells) as well as other antigen presenting cells (e.g., keratinocytes, endothelial cells, astrocytes, fibroblasts, oligodendrocytes).
  • the APC can be a cancer cell.
  • affinity refers to a measure of the strength of binding between two members of a binding pair (e.g., a human leukocyte antigen (HLA)-binding peptide and a class I or II HLA, or a peptide-HLA complex and a T cell receptor (TCR)).
  • HLA human leukocyte antigen
  • TCR T cell receptor
  • KD refers to the dissociation constant between two members of a binding pair and has units of molarity.
  • KA refers to the affinity constant between two members of a binding pair is the inverse of the dissociation constant. Affinity may be determined experimentally, for example by surface plasmon resonance (SPR) using commercially available Biacore SPR units.
  • Koff refers to the off-rate constant of two members of a binding pair, (e.g., the off- rate constant of an HLA-binding peptide and a class I or II HLA, or a peptide-HLA complex and a WSGR Docket No.50401-795.601 TCR).
  • binding data results may be expressed in terms of an “IC 50 .” Affinity may also be expressed as the inhibitory concentration 50 (IC 50 ), or the concentration at which 50% of a first member of a binding pair (e.g., a peptide) is displaced. Likewise, ln(IC 50 ) refers to the natural log of the IC 50 .
  • an IC 50 may be the concentration of a tested peptide in a binding assay at which 50% inhibition of binding of a labeled reference peptide is observed. Given the conditions in which the assays are run (e.g., limiting HLA protein concentrations and/or labeled reference peptide concentrations), these values can approximate K D values. Assays for determining binding are well known in the art and are described in detail, for example, in PCT publications WO 94/20127 and WO 94/03205, and other publications such Sidney et al., Current Protocols in Immunology 18.3.1 (1998); Sidney, et al., J. Immunol.154:247 (1995); and Sette, et al., Mol.
  • binding can be expressed relative to binding by a reference standard peptide. Binding can also be determined using other assay systems including those using: live cells (e.g., Ceppellini et al., Nature 339:392 (1989); Christnick et al., Nature 352:67 (1991); Busch et al., Int. Immunol.2:443 (1990); Hill et al., J. Immunol.147:189 (1991); del Guercio et al., J. Immunol.154:685 (1995)), cell free systems using detergent lysates (e.g., Cerundolo et al., J.
  • Synthetic epitopes can comprise artificial amino acid residues “amino acid mimetics,” such as D isomers of natural occurring L amino acid residues or non-natural amino acid residues such as cyclohexylalanine.
  • a derived or prepared epitope can be an analog of a native epitope.
  • the term “derived from” refers to the origin or source, and may include naturally occurring, recombinant, unpurified, purified or differentiated molecules or cells.
  • an expanded or induced antigen specific T cell may be derived from a T cell.
  • an expanded or induced antigen specific T cell may be derived from an antigen specific T cell in a biological sample.
  • a matured APC may be derived from a non-matured APC (e.g., an immature APC).
  • an APC may be derived from a monocyte (e.g., a CD14+ monocyte).
  • a WSGR Docket No.50401-795.601 dendritic cell may be derived from a monocyte (e.g., a CD14+ monocyte).
  • an APC may be derived from a bone marrow cell.
  • an “epitope” is the collective features of a molecule (e.g., a peptide’s charge and primary, secondary and tertiary structure) that together form a site recognized by another molecule (e.g., an immunoglobulin, T cell receptor, HLA molecule, or chimeric antigen receptor).
  • an epitope can be a set of amino acid residues involved in recognition by a particular immunoglobulin; a Major Histocompatibility Complex (MHC) receptor; or in the context of T cells, those residues recognized by a T cell receptor protein and/or a chimeric antigen receptor.
  • Epitopes can be prepared by isolation from a natural source, or they can be synthesized according to standard protocols in the art.
  • Synthetic epitopes can comprise artificial amino acid residues, amino acid mimetics, (such as D isomers of naturally-occurring L amino acid residues or non-naturally-occurring amino acid residues).
  • epitopes may be referred to in some cases as peptides or peptide epitopes.
  • the region with 100% sequence identity to a native sequence generally has a length of: less than or equal to 600 amino acid residues, less than or equal to 500 amino acid residues, less than or equal to 400 amino acid residues, less than or equal to 250 amino acid residues, less than or equal to 100 amino acid residues, less than or equal to 85 amino acid residues, less than or equal to 75 amino acid residues, less than or equal to 65 amino acid residues, and less than or equal to 50 amino acid residues.
  • an “epitope” described herein is comprised by a peptide having a region with less than 51 amino acid residues that has 100% sequence identity to a native peptide sequence, in any increment down to 5 amino acid residues; for example 50, 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residues.
  • a “T cell epitope” refers to a peptide sequence bound by an MHC molecule in the form of a peptide-MHC (pMHC) complex.
  • a peptide-MHC complex can be recognized and bound by a TCR of a T cell (e.g., a cytotoxic T-lymphocyte or a T-helper cell).
  • T cell includes CD4+ T cells and CD8+ T cells.
  • the term T cell also includes both T helper 1 type T cells and T helper 2 type T cells.
  • T cells may be generated by the method described in the application, for a clinical application.
  • T cells or adoptive T cells referred to here are cells isolated from a biological source, manipulated and cultured ex vivo and prepared into a drug candidate for a specific therapy such as a cancer, e.g., melanoma.
  • a drug candidate may be designated a drug product.
  • a drug product is selected from a number of drug candidates.
  • a drug product is a T cell, more specifically, a population of T cells, or more specifically a population of T cells with heterogeneous characteristics and subtypes.
  • a drug product may have a population of T cells comprising CD8+ T cells, CD4+ T cells, with cells at least above a certain exhibiting antigen specificity, a certain percentage of each exhibiting a memory phenotype, among others.
  • An “immune cell” refers to a cell that plays a role in the immune response. Immune cells are of hematopoietic origin, and include lymphocytes, such as B cells and T cells; natural killer cells; myeloid cells, such as monocytes, macrophages, eosinophils, mast cells, basophils, and granulocytes.
  • an “immunogenic” peptide or an “immunogenic” epitope or an “immunogenic” peptide epitope is a peptide that binds to an HLA molecule and induces a cell-mediated or humoral response, for example, a cytotoxic T lymphocyte (CTL) response, a helper T lymphocyte (HTL) response and/or a B lymphocyte response.
  • CTL cytotoxic T lymphocyte
  • HTL helper T lymphocyte
  • B lymphocyte response e.g., a B lymphocyte response.
  • Immunogenic peptides described herein are capable of binding to an HLA molecule and thereafter induce a cell-mediated or humoral response (e.g., a CTL (cytotoxic) response, or a HTL response) to the peptide.
  • a “protective immune response” or “therapeutic immune response” refers to a CTL and/or an HTL response to an antigen derived from a pathogenic antigen (e.g., a tumor antigen), which in some way prevents or at least partially arrests disease symptoms, side effects or progression.
  • the immune response can also include an antibody response which has been facilitated by the stimulation of helper T cells.
  • a “T cell receptor” (“TCR”) refers to a molecule, whether natural or partly or wholly synthetically produced, found on the surface of T lymphocytes (T cells) that recognizes an antigen bound to a major histocompatibility complex (MHC) molecule.
  • MHC major histocompatibility complex
  • TCR The ability of a T cells to recognize an antigen associated with various diseases (e.g., cancers) or infectious organisms is conferred by its TCR, which is made up of both an alpha ( ⁇ ) chain and a beta ( ⁇ ) chain or a gamma ( ⁇ ) and a delta ( ⁇ ) chain.
  • the proteins which make up these chains are encoded by DNA, which employs a unique mechanism for generating the tremendous diversity of the TCR.
  • This multi-subunit immune recognition receptor associates with the CD3 complex and binds peptides presented by the MHC class I and II proteins on the surface of antigen-presenting cells (APCs). Binding of a TCR to a peptide on an APC is a central event in T cell activation.
  • a “chimeric antigen receptor” or “CAR” refers to an antigen binding protein in that includes an immunoglobulin antigen binding domain (e.g., an immunoglobulin variable WSGR Docket No.50401-795.601 domain) and a T cell receptor (TCR) constant domain.
  • a “constant domain” of a TCR polypeptide includes a membrane-proximal TCR constant domain, a TCR transmembrane domain and/or a TCR cytoplasmic domain, or fragments thereof.
  • a CAR is a monomer that includes a polypeptide comprising an immunoglobulin heavy chain variable domain linked to a TCR ⁇ constant domain.
  • the CAR is a dimer that includes a first polypeptide comprising an immunoglobulin heavy or light chain variable domain linked to a TCR ⁇ or TCR ⁇ constant domain and a second polypeptide comprising an immunoglobulin heavy or light chain variable domain (e.g., a ⁇ or ⁇ variable domain) linked to a TCR ⁇ or TCR ⁇ constant domain.
  • a first polypeptide comprising an immunoglobulin heavy or light chain variable domain linked to a TCR ⁇ or TCR ⁇ constant domain
  • a second polypeptide comprising an immunoglobulin heavy or light chain variable domain (e.g., a ⁇ or ⁇ variable domain) linked to a TCR ⁇ or TCR ⁇ constant domain.
  • MHC Major Histocompatibility Complex
  • MHC major histocompatibility complex
  • MHC can include any class of MHC molecule, such as MHC class I and MHC class II molecules, and relate to a complex of genes which occurs in all vertebrates. In humans, the MHC complex is also known as the human leukocyte antigen (HLA) complex.
  • HLA human leukocyte antigen
  • a “Human Leukocyte Antigen” or “HLA” refers to a human Major Histocompatibility Complex (MHC) protein (see, e.g., Stites, et al., Immunology, 8TH Ed., Lange Publishing, Los Altos, Calif. (1994).
  • the major histocompatibility complex in the genome comprises the genetic region whose gene products expressed on the cell surface are important for binding and presenting endogenous and/or foreign antigens and thus for regulating immunological processes.
  • MHC proteins or molecules are important for signaling between lymphocytes and antigen presenting cells or diseased cells in immune reactions. MHC proteins or molecules bind peptides and present them for recognition by T- cell receptors.
  • the proteins encoded by the MHC can be expressed on the surface of cells, and display both self-antigens (peptide fragments from the cell itself) and non-self-antigens (e.g., fragments of invading microorganisms) to a T-cell.
  • MHC binding peptides can result from the proteolytic cleavage of protein antigens and represent potential lymphocyte epitopes. (e.g., T cell epitope and B cell epitope).
  • MHCs can transport the peptides to the cell surface and present them there to specific cells, such as cytotoxic T-lymphocytes, T-helper cells, or B cells.
  • the MHC region can be divided into three subgroups, class I, class II, and class III.
  • MHC class I proteins can contain an ⁇ -chain and ⁇ 2- microglobulin (not part of the MHC encoded by chromosome 15). They can present antigen fragments to cytotoxic T-cells.
  • MHC class II proteins can contain ⁇ - and ⁇ -chains and they can present antigen fragments to T-helper cells.
  • MHC class III region can encode for other immune components, such as complement components and cytokines.
  • the MHC can be both polygenic (there are several MHC class I and MHC class II genes) and polymorphic (there are multiple alleles of each gene).
  • WSGR Docket No.50401-795.601 [0301]
  • a “receptor” refers to a biological molecule or a molecule grouping capable of binding a ligand.
  • a receptor may serve, to transmit information in a cell, a cell formation or an organism.
  • a receptor comprises at least one receptor unit, for example, where each receptor unit may consist of a protein molecule.
  • a receptor has a structure which complements that of a ligand and may complex the ligand as a binding partner. The information is transmitted in particular by conformational changes of the receptor following complexation of the ligand on the surface of a cell.
  • a receptor is to be understood as meaning in particular proteins of MHC classes I and II capable of forming a receptor/ligand complex with a ligand, in particular a peptide or peptide fragment of suitable length.
  • a “ligand” refers to a molecule which has a structure complementary to that of a receptor and is capable of forming a complex with this receptor.
  • a ligand is to be understood as meaning a peptide or peptide fragment which has a suitable length and suitable binding motifs in its amino acid sequence, so that the peptide or peptide fragment is capable of forming a complex with MHC proteins such as MHC class I or MHC class II proteins.
  • a “receptor/ligand complex” is also to be understood as meaning a “receptor/peptide complex” or “receptor/peptide fragment complex”, including a peptide- or peptide fragment- presenting MHC molecule such as MHC class I or MHC class II molecules.
  • a “native” or a “wild type” sequence refers to a sequence found in nature.
  • the term “naturally occurring” as used herein refers to the fact that an object can be found in nature. For example, a peptide or nucleic acid that is present in an organism (including viruses) and can be isolated from a source in nature and which has not been intentionally modified by man in the laboratory is naturally occurring.
  • peptide and peptide epitope are used interchangeably with “oligopeptide” in the present specification to designate a series of residues connected one to the other, typically by peptide bonds between the ⁇ -amino and carboxyl groups of adjacent amino acid residues.
  • a “synthetic peptide” refers to a peptide that is obtained from a non-natural source, e.g., is man-made. Such peptides can be produced using such methods as chemical synthesis or recombinant DNA technology.
  • “Synthetic peptides” include “fusion proteins.”
  • the term “motif” refers to a pattern of residues in an amino acid sequence of defined length, for example, a peptide of less than about 15 amino acid residues in length, or less than about 13 amino acid residues in length, for example, from about 8 to about 13 amino acid residues (e.g., 8, 9, 10, 11, 12, or 13) for a class I HLA motif and from about 6 to about 25 amino acid residues (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25) for a class II HLA motif, which is recognized by a particular HLA molecule.
  • Motifs are typically different for each HLA protein encoded by a given human HLA allele. These motifs differ in their pattern of the primary and secondary anchor residues.
  • an MHC class I motif identifies a peptide of 7, 89, WSGR Docket No.50401-795.601 10, 11, 12 or 13 amino acid residues in length.
  • an MHC class II motif identifies a peptide of 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 amino acid residues in length.
  • a “cross-reactive binding” peptide refers to a peptide that binds to more than one member of a class of a binding pair members (e.g., a peptide bound by both a class I HLA molecule and a class II HLA molecule).
  • the term “residue” refers to an amino acid residue or amino acid mimetic residue incorporated into a peptide or protein by an amide bond or amide bond mimetic, or that is encoded by a nucleic acid (DNA or RNA). The nomenclature used to describe peptides or proteins follows the conventional practice.
  • amino group is presented to the left (the amino- or N-terminus) and the carboxyl group to the right (the carboxy- or C-terminus) of each amino acid residue.
  • amino acid residue positions are referred to in a peptide epitope, they are numbered in an amino to carboxyl direction with the first position being the residue located at the amino terminal end of the epitope, or the peptide or protein of which it can be a part.
  • the amino- and carboxyl-terminal groups although not specifically shown, are in the form they can assume at physiologic pH values, unless otherwise specified.
  • each residue is generally represented by standard three letter or single letter designations.
  • the L-form of an amino acid residue is represented by a capital single letter or a capital first letter of a three-letter symbol
  • the D-form for those amino acid residues having D-forms is represented by a lower case single letter or a lower case three letter symbol.
  • Glycine has no asymmetric carbon atom and is simply referred to as “Gly” or “G”.
  • the amino acid sequences of peptides set forth herein are generally designated using the standard single letter symbol.
  • a “conservative amino acid substitution” is one in which one amino acid residue is replaced with another amino acid residue having a similar side chain.
  • Families of amino acid residues having similar side chains have been defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine).
  • basic side chains e.g., lysine, arginine, histidine
  • acidic side chains e.g., aspartic acid
  • “Pharmaceutically acceptable” refers to a generally non-toxic, inert, and/or physiologically compatible composition or component of a composition.
  • a “pharmaceutical excipient” or “excipient” comprises a material such as an adjuvant, a carrier, pH-adjusting and buffering agents, tonicity adjusting agents, wetting agents, preservatives, and the like.
  • a “pharmaceutical excipient” is an excipient which is pharmaceutically acceptable.
  • the term “vaccine” relates to a pharmaceutical preparation (pharmaceutical composition) or product that upon administration induces an immune response, for example, a cellular or humoral immune response, which recognizes and attacks a pathogen or a diseased cell such as a cancer cell.
  • a vaccine may be used for the prevention or treatment of a disease.
  • polynucleotide and “nucleic acid” are used interchangeably herein and refer to polymers of nucleotides of any length, and include DNA and RNA, for example, mRNA.
  • the nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and/or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase.
  • the polynucleotide and nucleic acid can be in vitro transcribed mRNA.
  • the polynucleotide that is administered using the methods of the present disclosure is mRNA.
  • isolated or “biologically pure” refer to material which is substantially or essentially free from components which normally accompany the material as it is found in its native state.
  • isolated peptides described herein do not contain some or all of the materials normally associated with the peptides in their in situ environment.
  • an “isolated” epitope can be an epitope that does not include the whole sequence of the protein from which the epitope was derived.
  • a naturally-occurring polynucleotide or peptide present in a living animal is not isolated, but the same polynucleotide or peptide, separated from some or all of the coexisting materials in the natural system, is isolated.
  • Such a polynucleotide could be part of a vector, and/or such a polynucleotide or peptide could be part of a composition, and still be “isolated” in that such vector or composition is not part of its natural environment.
  • Isolated RNA molecules include in vivo or in vitro RNA transcripts of the DNA molecules described herein, and further include such molecules produced synthetically.
  • a polypeptide, antibody, polynucleotide, vector, cell, or composition which is isolated is substantially pure.
  • substantially pure refers to material which is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure.
  • the terms “identical” or percent “identity” in the context of two or more nucleic acids or polypeptides refer to two or more sequences or subsequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned (introducing gaps, if necessary) for maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity.
  • the percent identity can be measured using sequence comparison software or algorithms or by visual inspection.
  • Various algorithms and software that can be used to obtain alignments of amino acid or nucleotide sequences are well-known in the art. These include, but are not limited to, BLAST, ALIGN, Megalign, BestFit, GCG Wisconsin Package, and variations thereof.
  • two nucleic acids or polypeptides described herein are substantially identical, meaning they have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, and in some embodiments at least 95%, 96%, 97%, 98%, 99% nucleotide or amino acid residue identity, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection.
  • identity exists over a region of the sequences that is at least about 10, at least about 20, at least about 40-60 residues, at least about 60-80 residues in length or any integral value there between. In some embodiments, identity exists over a longer region than 60-80 residues, such as at least about 80-100 residues, and in some embodiments the sequences are substantially identical over the full length of the sequences being compared, such as an amino acid sequence of a peptide or a coding region of a nucleotide sequence.
  • subject refers to any animal (e.g., a mammal), including, but not limited to, humans, non-human primates, canines, felines, rodents, and the like, which is to be the recipient of a particular treatment. Typically, the terms “subject” and “patient” are used interchangeably herein in reference to a human subject.
  • effective amount or “therapeutically effective amount” or “therapeutic effect” refer to an amount of a therapeutic effective to “treat” a disease or disorder in a subject or mammal.
  • the therapeutically effective amount of a drug has a therapeutic effect and as such can prevent the development of a disease or disorder; slow down the development of a disease or disorder; slow down the progression of a disease or disorder; relieve to some extent one or more of the symptoms associated with a disease or disorder; reduce morbidity and mortality; improve quality of life; or a combination of such effects.
  • the terms “treating” or “treatment” or “to treat” or “alleviating” or “to alleviate” refer to both (1) therapeutic measures that cure, slow down, lessen symptoms of, and/or halt progression of a diagnosed pathologic condition or disorder and (2) prophylactic or preventative measures that prevent WSGR Docket No.50401-795.601 or slow the development of a targeted pathologic condition or disorder.
  • those in need of treatment include those already with the disorder; those prone to have the disorder; and those in whom the disorder is to be prevented.
  • a cell sample e.g., a peripheral blood mononuclear cell (PBMC) sample
  • PBMC peripheral blood mononuclear cell
  • an immune cell sample depleted of CD25 expressing cells refers to an immune cell sample in which CD25 expressing cells have been removed or depleted.
  • one or more binding agents can be used to remove or deplete one or more cells or cell types from a sample.
  • CD14+ cells can be depleted or removed from a PBMC sample, such as by using an antibody that binds to CD14.
  • the “stimulation” refers to a response induced by binding of a stimulatory molecule with its cognate ligand thereby mediating a signal transduction event.
  • stimulation of a T cell can refer to binding of a TCR of a T cell to a peptide-MHC complex.
  • stimulation of a T cell can refer to a step within protocol 1 or protocol 2 in which PBMCs are cultured together with peptide loaded APCs.
  • enriched refers to a composition or fraction wherein an object species has been partially purified such that the concentration of the object species is substantially higher than the naturally occurring level of the species in a finished product without enrichment.
  • induced cell refers to a cell that has been treated with an inducing compound, cell, or population of cells that affects the cell’s protein expression, gene expression, differentiation status, shape, morphology, viability, and the like.
  • a “reference” can be used to correlate and/or compare the results obtained in the methods of the present disclosure from a diseased specimen.
  • a “reference” may be obtained on the basis of one or more normal specimens, in particular specimens which are not affected by a disease, either obtained from an individual or one or more different individuals (e.g., healthy individuals), such as individuals of the same species.
  • a “reference” can be determined empirically by testing a sufficiently large number of normal specimens.
  • a tumor unless otherwise mentioned, is a cancerous tumor, and the terms cancer and tumor are used interchangeably throughout the document. While a tumor is a cancer of solid tissue, several of the compositions and methods described herein are in principle applicable to cancers of the blood, leukemia.
  • T cells e.g., ex vivo activated T cells, or T-cell receptor engineered T cells (TCR-T cells)
  • TCR-T cells T-cell receptor engineered T cells
  • the cells can circulate until they encounter their cognate epitope, typically on a tumor cell.
  • T WSGR Docket No.50401-795.601 cells can infiltrate the tumor and survive the harsh tumor microenvironment.
  • infused T cell numbers and frequency may decline relatively rapidly after infusion.
  • the dose of infused TCR-T cells may be important in clinical response across several studies.
  • One strategy to support the engraftment, expansion and persistence of infused T cells after infusion can include administering a vaccine that encodes the target antigen.
  • the vaccine design can differ and may be a determinant of the success of this approach.
  • the vaccine may encode for the full-length protein to be presented on the surface of cells.
  • the vaccine strings designed to lead to optimal cleavage of the target epitopes can lead to more (e.g., 10-100 times more) of the desired epitope being presented on major histocompatibility complex (MHC) molecules encoded by HLA alleles than when the full-length RAS protein is used.
  • MHC major histocompatibility complex
  • the full-length RAS polypeptide can be a full-length KRAS, NRAS or HRAS polypeptide.
  • the vaccine may encode targets epitopes presented by MHC molecules encoded by HLA- A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA- C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-DRB1*11:01, HLA-A*03:02, HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, and HLA-A*03:05.
  • vaccine constructs to present at least the target epitope on each of these HLA alleles.
  • a series of in vitro and in vivo assays have been defined to prioritize and select the best vaccine design, starting by choosing the best codon optimization approach and then selecting the best order of the epitopes. This information can be used to evaluate the approach in vivo.
  • a mouse model for this approach can utilize mice expressing human HLA and MHC.
  • HLA-engineered tumor cells can also be utilized to evaluate the approach.
  • RAS vaccines comprising RAS polypeptides or recombinant nucleic acids encoding RAS polypeptides that, when expressed, can result in presentation of one or more epitopes of RAS by one or more MHC molecules encoded by one or more HLA alleles.
  • a recombinant nucleic acid encoding a RAS polypeptide comprising a multiepitopic polypeptide.
  • the RAS polypeptide does not comprise a full- length RAS polypeptide.
  • the RAS polypeptide comprises a first RAS amino acid sequence comprising a first RAS epitope sequence.
  • the RAS polypeptide comprises a second RAS amino acid sequence comprising a second RAS epitope sequence.
  • the first RAS epitope sequence and the second RAS epitope sequence are different.
  • the first RAS epitope sequence and the second RAS epitope sequence are linked via a linker.
  • presentation of the first and/or second RAS epitope sequence as a peptide:MHC complex by the antigen presenting cells (APCs) of the subject administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide is higher than the presentation of the first and/or second RAS epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide.
  • the first RAS amino acid sequence is the first epitope sequence.
  • the second RAS amino acid sequence is the second epitope sequence.
  • the first RAS amino acid sequence is the first epitope sequence and the second RAS amino acid sequence is the second epitope sequence. In some embodiments, the first RAS amino acid sequence consists of the first epitope sequence. In some embodiments, the second RAS amino acid sequence consists of the second epitope sequence. In some embodiments, the first RAS amino acid sequence consists of the first epitope sequence and the second RAS amino acid sequence consists of the second epitope sequence. In some cases, each different RAS epitope sequence is separated by a linker. [0325] In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation. In some embodiments, the second RAS amino acid sequence comprises a second RAS mutation.
  • the second RAS mutation is different from the first RAS mutation. In some embodiments, the second RAS mutation is same as the first RAS mutation. In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation, and the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation. In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation, and the second RAS amino acid sequence comprises a second RAS mutation same as the first RAS mutation. [0326] In some embodiments, the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C. In some embodiments, the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C.
  • the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell.
  • the first RAS mutation is G12V, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72.
  • the first RAS mutation is G12D, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79.
  • the first RAS mutation is G12C, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096.
  • the first RAS epitope sequence first RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to WSGR Docket No.50401-795.601 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide.
  • the second RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide. [0328]
  • the first RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide.
  • the second RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide.
  • the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker.
  • the first RAS amino acid sequence comprises the first RAS epitope sequence and one, two, three, four, five or more residues flanking the N-terminus or C-terminus of the first RAS epitope sequence from the full length RAS polypeptide.
  • the second RAS amino acid sequence comprises the second RAS epitope sequence and one, two, three, four, five or more residues flanking the N-terminus or C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide.
  • the multiepitopic polypeptide does not comprise more than 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more consecutive amino acids from the full-length RAS polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise more than 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more consecutive amino acids from the full-length RAS polypeptide.
  • the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a secretory (Sec) sequence.
  • the Sec sequence is at the N terminus of the multiepitopic polypeptide.
  • the Sec sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80% , at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 32.
  • the Sec sequence comprises a sequence of SEQ ID NO: 32.
  • the Sec sequence is operably linked to the multiepitopic polypeptide via a linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 30. In some embodiments, the linker comprises a sequence of SEQ ID NO: 30. In some embodiments, the Sec sequence is operably linked to the multiepitopic polypeptide via a linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112.
  • the linker comprises a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence having at least 60%, at least WSGR Docket No.50401-795.601 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 30. In some cases, the linker comprises a sequence of SEQ ID NO: 31.
  • the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MHC I Trafficking Domain (MITD) sequence.
  • the sequence encoding an MITD sequence is at the C terminus of the multiepitopic polypeptide.
  • the MITD sequence comprises at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 33.
  • the MITD sequence comprises a sequence of SEQ ID NO: 33.
  • the multiepitopic polypeptide is operably linked to the MITD domain.
  • the multiepitopic polypeptide is operably linked to the MITD domain via a linker sequence.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 30.
  • the linker comprises a sequence of SEQ ID NO: 30.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112.
  • the linker comprises a sequence of SEQ ID NO: 112.
  • the multiepitopic polypeptide comprises a RAS polypeptide.
  • the sequence of the multiepitopic polypeptide is the same RAS epitope sequence.
  • the sequence of the multiepitopic polypeptide is a different RAS epitope sequence.
  • the multiepitopic polypeptide comprises at least 2 different RAS epitope sequences.
  • the multiepitopic polypeptide comprises at least 3 different RAS epitope sequences.
  • the multiepitopic polypeptide comprises at least 4 different RAS epitope sequences.
  • the multiepitopic polypeptide comprises at least 5 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 6 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 8 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 9 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 10 or more different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide is a RAS polypeptide comprising the first RAS epitope sequence and the second RAS epitope sequence.
  • the multiepitopic polypeptide comprises a first RAS epitope sequence, operably linked to a second RAS epitope sequence.
  • the first RAS epitope WSGR Docket No.50401-795.601 sequence and the second RAS epitope sequence are the same.
  • the first RAS epitope sequence and the second RAS epitope sequence are different.
  • the first RAS epitope sequence and second RAS epitope sequence are presentable by different HLA alleles.
  • the first RAS epitope sequence and second RAS epitope sequence are presented by different HLA alleles.
  • the first RAS epitope sequence and second RAS epitope sequence are predicted to bind to different HLA alleles. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are predicted to be presented by different HLA alleles. [0335] In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 500nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 400nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 300nM.
  • a first RAS epitope sequence binds to a first HLA allele. In some embodiments, a first RAS epitope sequence is predicted to bind to a first HLA allele. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 200nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 100nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 50nM.
  • a first RAS epitope sequence binds to a first HLA allele with a KD less than 1nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele. In some embodiments, a first RAS epitope sequence is predicted to bind to a second HLA allele. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 200nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 300nM.
  • a first RAS epitope sequence binds to a second HLA allele with a KD of more than 500nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 600nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 700nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 800nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 900nM.
  • a first RAS epitope sequence binds to a second HLA allele with a KD of more than 1000nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 1nM and binds to second HLA allele with a KD of more than 200nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 50nM and binds to second HLA allele with a KD of more than 300nM.
  • a first RAS epitope sequence binds to a first HLA allele with a KD of less than 100nM and binds to second HLA allele with a KD of more than 500nM.
  • a first WSGR Docket No.50401-795.601 RAS epitope sequence binds to a first HLA allele with a KD of less than 200 nM and binds to second HLA allele with a KD of more than 600 nM.
  • the linker comprises at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112.
  • the multiepitopic polypeptide comprises a first RAS epitope sequence, operably linked to a second RAS epitope sequence, operably linked to a third RAS epitope sequence.
  • the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*11:01 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*11:01 allele.
  • the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*11:01 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*11:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*11:01 allele. [0339] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*03:01 allele.
  • the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*03:01 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*03:01 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*03:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*03:01 allele. [0340] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele.
  • the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*30:01 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*30:01 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*30:01 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*30:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*30:01 allele.
  • the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*68:01 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*68:01 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*68:01 allele.
  • the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*68:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*68:01 allele. [0342] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-B allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-B*40:01 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-B*40:01 allele.
  • the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- B*40:01 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-B*40:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-B*40:01 allele. [0343] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*01:02 allele.
  • the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*01:02 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*01:02 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*01:02 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*01:02 allele. [0344] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele.
  • the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*03:03 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*03:03 allele.
  • the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the first RAS epitope WSGR Docket No.50401-795.601 sequence is presented by an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*03:04 allele.
  • the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*03:04 allele. [0346] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-DRB1 allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-DRB1*07:01 allele.
  • the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-DRB1*07:01 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA-DRB1*07:01 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-DRB1*07:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA- DRB1*07:01 allele.
  • the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*03:02 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*03:02 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*03:02 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*03:02 allele.
  • the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*03:02 allele. [0348] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*03:05 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*03:05 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*03:05 allele.
  • the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*03:05 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*03:05 allele.
  • the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-B allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-B*07:02 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-B*07:02 allele.
  • the second RAS epitope sequence binds to an MHC molecule encoded by an HLA- WSGR Docket No.50401-795.601 B*07:02 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-B*07:02 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-B*07:02 allele. [0350] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele.
  • the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*03:04 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*03:04 allele.
  • the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*05:01 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*05:01 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*05:01 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*05:01 allele.
  • the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*05:01 allele. [0352] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*-3:01 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*-3:01 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA-A*- 3:01 allele.
  • the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*-3:01 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*-3:01 allele. [0353] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*-11:01 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*-11:01 allele.
  • the second RAS epitope sequence binds to an MHC molecule encoded by an HLA-A*- 11:01 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*-11:01 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*-11:01 allele. WSGR Docket No.50401-795.601 [0354] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele.
  • the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*-68:01 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*-68:01 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA-A*- 68:01 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*-68:01 allele.
  • the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*-68:01 allele. [0355] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*08:02 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*08:02 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*08:02 allele.
  • the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*08:02 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*08:02 allele. [0356] In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-DRB allele. In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-DRB1*11:01 allele.
  • the third RAS epitope sequence is presented by an MHC molecule encoded by an HLA-DRB1*11:01 allele. In some embodiments, the third RAS epitope sequence binds to an MHC molecule encoded by an HLA-DRB1*11:01 allele. In some embodiments, the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-DRB1*11:01 allele. In some embodiments, the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA- DRB1*11:01 allele.
  • the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*3:01 allele. In some embodiments, the third RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*3:01 allele. In some embodiments, the third RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*3:01 allele. In some embodiments, the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*3:01 allele.
  • the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*3:01 allele. [0358] In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the third RAS epitope sequence is presentable by WSGR Docket No.50401-795.601 an MHC molecule encoded by an HLA-A*11:01 allele. In some embodiments, the third RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*11:01 allele.
  • the third RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*11:01 allele. In some embodiments, the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*11:01 allele. In some embodiments, the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*11:01 allele. [0359] In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*68:01 allele.
  • the third RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*68:01 allele. In some embodiments, the third RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*68:01 allele. In some embodiments, the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*68:01 allele. In some embodiments, the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*68:01 allele. [0360] In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele.
  • the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the third RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the third RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*03:03 allele. In some embodiments, the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*03:03 allele.
  • the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2])x-CT seq, where x is an integer from 1 to 50. In some embodiments, the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2])x-CT seq, where x is an integer from 1 to 25. In some embodiments, the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1- [Antigen2])x-CT seq, where x is an integer from 1 to 10.
  • the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2]-cleavable linker2-[Antigen3])x-CT seq, where x is an integer from 1 to 50. In some embodiments, the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2]-cleavable linker2-[Antigen3])x-CT seq, where x is an integer from 1 to 25.
  • the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2]-cleavable linker2-[Antigen3])x-CT seq, where x is an integer from 1 to 10.
  • NT seq comprises a secretory (Sec) sequence and a N-terminal linker sequence.
  • CT seq comprises a C-terminal linker and a MITD sequence.
  • the Antigen1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 27-29.
  • the Antigen2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 27-29.
  • the Antigen3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 27- 29.
  • the cleavable linker1 or cleavable linker2 comprise a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to any one of SEQ ID NOs: 30 or 31.
  • the cleavable linker1 or cleavable linker2 is selected from the group consisting of SEQ ID NOs: 30 and 31.
  • the N-terminal linker sequence is selected from the group consisting of SEQ ID NOs: 30 and 31. In some embodiments, the C-terminal linker sequence is selected from the group consisting of SEQ ID NOs: 30 and 31.
  • the RAS polypeptide comprises a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises a sequence with at least 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises a sequence with at least 90% sequence identity to SEQ ID NO: 75.
  • the RAS polypeptide comprises a sequence of SEQ ID NO: 27. [0365] In some embodiments, the RAS polypeptide comprises a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises a sequence with at least 80% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises a sequence of SEQ ID NO: 28.
  • the RAS polypeptide comprises a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises a sequence of SEQ ID NO: 29. [0367] In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27.
  • the RAS polypeptide comprises one or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least WSGR Docket No.50401-795.601 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 27. [0368] In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28.
  • the RAS polypeptide comprises one or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 80% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 28. [0369] In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29.
  • the RAS polypeptide comprises one or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 29. [0370] In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27.
  • the RAS polypeptide comprises two copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 27. [0371] In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28.
  • the RAS polypeptide comprises two copies of a sequence with at least 80% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 28. [0372] In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29.
  • the RAS polypeptide comprises two copies of a sequence with at least 80% sequence identity to SEQ WSGR Docket No.50401-795.601 ID NO: 29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 29. [0373] In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27.
  • the RAS polypeptide comprises three copies of a sequence with at least 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 27. [0374] In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 80% sequence identity to SEQ ID NO: 28.
  • the RAS polypeptide comprises three copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 28. [0375] In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29.
  • the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 29. [0376] In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises four copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 80% sequence WSGR Docket No.50401-795.601 identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 28.
  • the RAS polypeptide comprises four copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 29.
  • the RAS polypeptide comprises five copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises five copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 80% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 28.
  • the RAS polypeptide comprises five copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 29.
  • the RAS polypeptide comprises six or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least WSGR Docket No.50401-795.601 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises six or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 80% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence of SEQ ID NO: 28.
  • the RAS polypeptide comprises six or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence of SEQ ID NO: 29.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 operably linked
  • the RAS polypeptide comprises, from N terminus to C terminus, WSGR Docket No.50401-795.601 the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 29 via a linker, and the sequence of SEQ ID NO: 29 operably linked to the sequence of SEQ ID NO: 28 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31.
  • the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO:
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 operably linked to the sequence of SEQ ID NO: 27 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112.
  • the linker comprises a sequence of SEQ ID NO: 112.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29.
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 29.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO:
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 operably linked to the sequence of SEQ ID NO: 29 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112.
  • the linker comprises a sequence of SEQ ID NO: 112.
  • WSGR Docket No.50401-795.601 [0391]
  • the RAS polypeptide comprises two copies of a multiepitopic polypeptide.
  • each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises three copies of a multiepitopic polypeptide.
  • each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises four copies of a multiepitopic polypeptide.
  • each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises five copies of a multiepitopic polypeptide.
  • each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises six copies of a multiepitopic polypeptide.
  • each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises seven copies of a multiepitopic polypeptide.
  • each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 14.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 14.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 16.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID WSGR Docket No.50401-795.601 NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 16.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 17.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 17.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 18.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 18.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 19.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS WSGR Docket No.50401-795.601 polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 19.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 20.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 20.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 21.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 21.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a WSGR Docket No.50401-795.601 sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 23.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 23.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 84.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 84.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 86.
  • the recombinant nucleic WSGR Docket No.50401-795.601 acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 86.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 88.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 88.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 92.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 92.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 93.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% WSGR Docket No.50401-795.601 sequence identity to a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 93.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 93. [0414] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 94.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 94.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 96.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 96.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 97.
  • the WSGR Docket No.50401-795.601 recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 97.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 97. [0417] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 98.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 98.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 100.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 100.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 101.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence WSGR Docket No.50401-795.601 having at least 60% sequence identity to a sequence of SEQ ID NO: 101.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 101.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 101.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 102.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 102.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 104.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 104.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 105.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 105.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 105.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 106.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 106.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at WSGR Docket No.50401-795.601 least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 109.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 109.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 109.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100- 102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a WSGR Docket No.50401-795.601 sequence of SEQ ID NO: 16.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 17.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 19.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 21.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 23.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 86.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 92.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, WSGR Docket No.50401-795.601 at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 93.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 94.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 97.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 100.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 102.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 105.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 108.
  • the recombinant nucleic acid encoding the RAS WSGR Docket No.50401-795.601 polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 109.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences with at least 90% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104- 106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 14.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 17.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 20.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 23.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ WSGR Docket No.50401-795.601 ID NO: 88.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 94.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 98.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 102.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 106.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14- 23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID WSGR Docket No.50401-795.601 NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 19.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 23.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 92.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 97.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 102.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 105. In some embodiments, WSGR Docket No.50401-795.601 the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 110. [0430] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 18.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 88.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 96.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide WSGR Docket No.50401-795.601 comprises two copies of a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 101.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 106.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 20.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 84.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 88. WSGR Docket No.50401-795.601 In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 93.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 98.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 104.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 109.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 110. [0432] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 14.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 19.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid WSGR Docket No.50401-795.601 encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 23.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 92.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 97.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 102.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 110. [0433] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a WSGR Docket No.50401-795.601 sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 17.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 21.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 86.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 94.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 100.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 105.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 108. In some embodiments, the recombinant WSGR Docket No.50401-795.601 nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 20.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 84.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 93.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 98.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 101. WSGR Docket No.50401-795.601 In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 104.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 109.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence having
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence selected from the group consisting of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected WSGR Docket No.50401-795.601 from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 90% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence having at least 90% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence identity the sequence selected from the group consisting of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 operably linked to a sequence selected from the group consisting of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence.
  • the linker sequence encodes a cleavable linker.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence WSGR Docket No.50401-795.601 identity to a sequence of SEQ ID NO: 9.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 8.
  • the linker sequence comprises a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 13.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 80% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence having at least 80% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence having at least 80% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: WSGR Docket No.50401-795.601 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%,
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence selected from the group consisting of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence.
  • the linker sequence encodes a cleavable linker.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or WSGR Docket No.50401-795.601 100% sequence identity to a sequence of SEQ ID NO: 10.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 14.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 9.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 8.
  • the linker sequence comprises a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 13.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at WSGR Docket No.50401
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence selected from the group consisting of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence and the sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-19, via a linker sequence and the sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence and the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence selected from the group consisting of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence.
  • the linker sequence encodes a cleavable linker.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 9.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 6.
  • the linker sequence comprises a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 13. WSGR Docket No.50401-795.601 [0456] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises at least two copies of a string of sequences.
  • each string of sequences comprises, 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of
  • each string of sequences comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108.
  • each string of sequences comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of the string of sequences.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises seven copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises eight copies of the string of sequences.
  • the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a secretory (Sec) sequence.
  • the Sec sequence is at the 5’ end of the string of sequences.
  • the Sec sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 3.
  • the Sec sequence comprises a sequence of SEQ ID NO: 3.
  • the sequence encoding the Sec sequence is operably linked to the string of sequences via a linker sequence.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89.
  • the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89.
  • the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MHC I Trafficking Domain (MITD) sequence.
  • the sequence encoding an MITD sequence is at the 3’ end of the string of sequences.
  • the MITD sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 24 or 90.
  • the MITD sequence comprises a sequence of SEQ ID NO: 24 or 90.
  • the string of sequences is operably linked to the sequence encoding the MITD domain. In some embodiments, the string of sequences is operably linked to the sequence encoding the MITD domain via a linker sequence.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. In some embodiments, the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89.
  • a recombinant nucleic acid comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 1.
  • the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 2.
  • the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 95.
  • the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, WSGR Docket No.50401-795.601 at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 103.
  • the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 111. [0460] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 1.
  • the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 95. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 103.
  • the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 111. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 1.
  • the recombinant nucleic acid comprises a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 95. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 103.
  • the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 111.
  • Immune Cells e.g., T cells
  • T cell receptors can also comprise endogenous T cell receptors WSGR Docket No.50401-795.601 that have been activated. Immune cells expressing a TCR can be activated and/or expanded using methods such as NEO-STIM.
  • T cell receptors can comprise receptors encoded by recombinant nucleic acids that are specific for a RAS polypeptide or fragment thereof.
  • a recombinant nucleic acid encoding a TCR is provided herein.
  • the TCR comprises a TCR beta chain construct.
  • the TCR comprises a TCR alpha chain construct.
  • the TCR comprises a TCR beta chain construct and a TCR alpha chain construct.
  • the TCR binds to a peptide:MHC complex.
  • the peptide:MHC complex comprises a RAS epitope sequence having at least 5 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 27, 58-62 and 65-72 and a human MHC encoded by an HLA allele selected from the group consisting of HLA- A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA- C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05.
  • the peptide:MHC complex comprises a RAS epitope sequence having at least 7 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 27, 58-62 and 65-72 and a human MHC encoded by an HLA allele selected from the group consisting of HLA- A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA- C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05.
  • the peptide:MHC complex comprises a RAS epitope sequence having at least 5 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 28, 75-79 and a human MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01.
  • the peptide:MHC complex comprises a RAS epitope sequence having at least 7 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 28, 75-79 and a human MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01.
  • the peptide:MHC complex comprises a RAS epitope sequence having at least 5 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 29, 81, 82, and 1096 and a human MHC encoded by an HLA allele selected from the group consisting of HLA- DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03.
  • the peptide:MHC complex comprises a RAS epitope sequence having at least 7 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 29, 81, 82, and 1096 and a human MHC encoded by an HLA allele selected from the group consisting of HLA- DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least WSGR Docket No.50401-795.601 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 58.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 59.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 60.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 61.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 62.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 65. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 66. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 67.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 68. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 69.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 70.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 71.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 72.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 75.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence WSGR Docket No.50401-795.601 identity to a sequence of SEQ ID NO: 76.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 77.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 78. In some embodiments the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 79.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 29.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 81.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 82.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 1096.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 58. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 59. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 60. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 61.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 62. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 65. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 66. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 67.
  • the peptide:MHC complex WSGR Docket No.50401-795.601 comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 68. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 69. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 70. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 71.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 72. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 75. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 76. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 77.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 78. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 79. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 29. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 81.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 82. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 1096. [0465] In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 58. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 59.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 60. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 61. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 62. In some embodiments the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 65. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 66.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 67. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 68. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 69. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 70. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 71.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 72. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 75. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 76. In some embodiments the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 77. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 78.
  • the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 79. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 29. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 81. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 82. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 1096.
  • the cell comprising the recombinant nucleic acids presented herein.
  • the cell is an immune cell.
  • the cell is a myeloid lineage cell.
  • the cell is a lymphocyte.
  • the cell is a B cell.
  • the cell is a T cell.
  • the proinflammatory cytokine is IFN- ⁇ .
  • the proinflammatory cytokine is TNF- ⁇ .
  • the proinflammatory cytokine is IL-12.
  • the proinflammatory cytokine is IL-6. In some cases, the proinflammatory cytokine is IL-17. In some embodiments, the proinflammatory cytokine is a chemokine. In some cases, upon binding of the TCR to the peptide:MHC complex, cell division is increased. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex.
  • cytotoxicity of the cell against target cell is increased by 2% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex.
  • cytotoxicity of the cell against target cell is increased by 5% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex.
  • cytotoxicity of the cell against target cell is increased by 10% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 15% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 25% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex.
  • cytotoxicity of the cell against target cell is increased by 50% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 100% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 150% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex.
  • cytotoxicity of the cell against target cell is increased by 200% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 500% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex.
  • a recombinant nucleic acid encoding a TCR comprising a TCR beta chain construct. In some embodiments, the recombinant nucleic acid encoding a TCR comprises a TCR alpha chain construct.
  • the beta chain construct comprises a complementarity determining region 3 (CDR3).
  • CDR3 complementarity determining region 3
  • the beta chain CDR3 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 57.
  • the beta chain CDR3 comprises an amino acid sequence set forth in SEQ ID NO: 57.
  • the TCR beta chain construct comprises a variable region comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to identity to an amino acid sequence set forth in SEQ ID NO: 52 or SEQ ID NO: 53.
  • the TCR beta chain construct comprises a variable region comprising a sequence having at least 80% sequence identity to WSGR Docket No.50401-795.601 an amino acid sequence set forth in SEQ ID NO: 52 or SEQ ID NO: 53.
  • the TCR beta chain construct comprises a variable region comprising an amino acid sequence set forth in SEQ ID NO: 52 or SEQ ID NO: 53.
  • the TCR beta chain construct comprises a complementarity determining region 1 (CDR1) having an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 55 and a complementarity determining region 2 (CDR2) having an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 56.
  • CDR1 complementarity determining region 1
  • CDR2 complementarity determining region 2
  • the TCR beta chain construct comprises a complementarity determining region 1 (CDR1) having an amino acid sequence set forth in SEQ ID NO: 55 and a complementarity determining region 2 (CDR2) having an amino acid set forth in SEQ ID NO: 56.
  • the TCR alpha chain construct comprises a CDR1, a CDR2, and a CDR3.
  • the CDR1 comprises an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence set forth in SEQ ID NO: 46
  • the CDR2 comprises an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to identity toa sequence set forth in SEQ ID NO: 47
  • the CDR3 comprises an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence set forth in SEQ ID NO: 48.
  • the CDR1 comprises an amino acid sequence set forth in SEQ ID NO: 46
  • the CDR2 comprises an amino acid sequence set forth in SEQ ID NO: 47
  • the CDR3 comprises an amino acid sequence set forth in SEQ ID NO: 48.
  • the TCR alpha chain construct comprises a variable region comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to identity to an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44.
  • the TCR alpha chain construct comprises a variable region comprising a sequence having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44. In some embodiments, the TCR alpha chain construct comprises a variable region comprising an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44.
  • the TCR comprises a beta chain having an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to SEQ ID NO: 49 or SEQ ID NO: 51 and an alpha chain having an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to SEQ ID NO: 40 or SEQ ID NO: 42.
  • the TCR comprises a beta chain having an amino acid WSGR Docket No.50401-795.601 sequence that is at least 80% identical to SEQ ID NO: 49 or SEQ ID NO: 51 and an alpha chain having an amino acid sequence that is at least 80% identical to SEQ ID NO: 40 or SEQ ID NO: 42.
  • the TCR comprises a beta chain having an amino acid sequence set forth in SEQ ID NO: 49 or SEQ ID NO: 51 and an alpha chain having an amino acid sequence set forth in SEQ ID NO: 40 or SEQ ID NO: 42.
  • Non- limiting examples of cancers to be treated by the methods of the present disclosure can include melanoma (e.g., metastatic malignant melanoma), renal cancer (e.g., clear cell carcinoma), prostate cancer (e.g., hormone refractory prostate adenocarcinoma), pancreatic adenocarcinoma, breast cancer, colon cancer, lung cancer (e.g., non-small cell lung cancer), cutaneous melanoma, synovial sarcoma, myxoid and round cell liposarcoma, osteosarcoma, and neuroblastoma ,esophageal cancer, squamous cell carcinoma of the head and neck, liver cancer, ovarian cancer, cervical cancer, thyroid cancer, glioblastoma, glioma, leukemia, lymphoma, and other neoplastic malignancies.
  • melanoma e.g., metastatic malignant melanoma
  • renal cancer e.g.
  • a cancer to be treated by the methods of treatment of the present disclosure is selected from the group consisting of carcinoma, squamous carcinoma, adenocarcinoma, sarcomata, endometrial cancer, breast cancer, ovarian cancer, cervical cancer, fallopian tube cancer, primary peritoneal cancer, colon cancer, colorectal cancer, squamous cell carcinoma of the anogenital region, melanoma and renal cell carcinoma.
  • cancers that can be prevented and/or treated in accordance with present disclosure include, but are not limited to, the following: renal cancer, kidney cancer, glioblastoma multiforme, metastatic breast cancer; breast carcinoma; breast sarcoma; neurofibroma; neurofibromatosis; pediatric tumors; neuroblastoma; malignant melanoma; carcinomas of the epidermis; leukemias such as but not limited to, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemias such as myeloblastic, promyelocytic, myelomonocytic, monocytic, erythroleukemia leukemias and myclodysplastic syndrome, chronic leukemias such as but not limited to, chronic myelocytic (granulocytic) leukemia, chronic lymphocytic leukemia, hairy cell leukemia; polycythemia vera; lymphomas such as but not limited to Hod
  • cancers include myxosarcoma, osteogenic sarcoma, endotheliosarcoma, lymphangioendotheliosarcoma, mesothelioma, synovioma, hemangioblastoma, epithelial carcinoma, cystadenocarcinoma, bronchogenic carcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma and papillary adenocarcinomas.
  • Cancers include, but are not limited to, B cell cancer, e.g., multiple myeloma, Waldenstrom’s macroglobulinemia, the heavy chain diseases, such as, for example, alpha chain disease, gamma chain disease, and mu chain disease, benign monoclonal gammopathy, and immunocytic amyloidosis, melanomas, breast cancer, lung cancer, bronchus cancer, colorectal cancer, prostate cancer (e.g., metastatic, hormone refractory prostate cancer), pancreatic cancer, stomach cancer, ovarian cancer, urinary bladder cancer, brain or central nervous system cancer, peripheral nervous system cancer, esophageal cancer, cervical cancer, uterine or endometrial cancer, cancer of the oral cavity or pharynx, liver cancer, kidney cancer, testicular cancer, biliary tract cancer, small bowel or appendix cancer, salivary gland cancer, thyroid gland cancer, adrenal gland cancer, osteosarcoma, chondrosarcoma, cancer of hematological
  • the cancer whose phenotype is determined by the method of the present disclosure is an epithelial cancer such as, but not limited to, bladder cancer, breast cancer, cervical cancer, colon cancer, gynecologic cancers, renal cancer, laryngeal cancer, lung cancer, oral cancer, head and neck cancer, ovarian cancer, pancreatic cancer, prostate cancer, or skin cancer.
  • the cancer is breast cancer, prostate cancer, lung cancer, or colon cancer.
  • the epithelial cancer is non-small-cell lung cancer, nonpapillary renal cell carcinoma, cervical carcinoma, ovarian carcinoma (e.g., serous ovarian carcinoma), or breast carcinoma.
  • the epithelial cancers may be characterized in various other ways including, but not limited to, serous, endometrioid, mucinous, clear cell, brenner, or undifferentiated.
  • the present disclosure is used in the treatment, diagnosis, and/or prognosis of lymphoma or its subtypes, including, but not limited to, mantle cell lymphoma. Lymphoproliferative disorders are also considered to be proliferative diseases.
  • the present disclosure provides a method of treating a subject with a disease or condition.
  • the disease or condition can comprise a cancer.
  • the method can comprise administering to the subject a therapy comprising a multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide.
  • the multiepitopic polypeptide can comprise a RAS polypeptide.
  • the RAS polypeptide may not be a full-length RAS polypeptide.
  • each sequence of the multiepitopic polypeptide can be a different RAS epitope sequence.
  • the antigen presenting cells (APCs) of the subject administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide can present a RAS epitope sequence as a peptide:MHC complex.
  • the APCs of the subject present more of a RAS epitope sequence compared to the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide.
  • the APCs of the subject express more peptide:MHC complexes comprising the RAS epitope sequence compared to the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide.
  • the APCs of the subject express more of the RAS epitope sequence compared to the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide.
  • the full-length RAS polypeptide is a full-length KRAS, NRAS or HRAS polypeptide.
  • the therapy comprises a cell comprising the multiepitopic polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide.
  • the WSGR Docket No.50401-795.601 multiepitopic polypeptide comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence. In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence are different.
  • the presentation of the first and/or second RAS epitope sequence as a peptide:MHC complex by APCs of the subject administered the therapy is higher than the presentation of the first and/or second RAS epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide.
  • the full-length RAS polypeptide is a full-length KRAS, NRAS or HRAS polypeptide.
  • the first RAS amino acid sequence is a first KRAS, NRAS or HRAS amino acid sequence.
  • the second RAS amino acid sequence is a second KRAS, NRAS or HRAS amino acid sequence.
  • the APCs of the subject administered with the multiepitopic polypeptide having different RAS epitopes can present more (e.g., at least 1.1 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 5.5 times, 6 times, 6.5 times, 7 times, 7.5 times, 8 times, 8.5 times, 9 times, 9.5 times, 10 times, 20 times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times, 100 times, 120 times, 150 times, 200 times or more) of a RAS epitope sequence compared to the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide.
  • Presentation can be measured by mass spectrometry detecting RAS -specific MHC molecules following lysis and protein extraction of APCs. Presentation can also be measured by mass spectrometry detecting components of the RAS epitope sequence.
  • the APCs having (e.g., transfected or otherwise delivered with) the multiepitopic polypeptide having different RAS epitopes can present more (e.g., at least 1.1 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 5.5 times, 6 times, 6.5 times, 7 times, 7.5 times, 8 times, 8.5 times, 9 times, 9.5 times, 10 times, 20 times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times, 100 times, 120 times, 150 times, 200 times or more) of a RAS epitope sequence compared to the APCs having the full-length RAS polypeptide or a recombinant nucleic acid encoding the full
  • Presentation can be measured by mass spectrometry detecting RAS -specific MHC molecules following lysis and protein extraction of APCs. Presentation can also be measured by mass spectrometry detecting components of the RAS epitope sequence.
  • the method further comprises administering to the subject a T-cell receptor (TCR) or a cell comprising the TCR. In some embodiments, the method comprises administering to the subject a recombinant nucleic acid encoding the TCR or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR.
  • TCR T-cell receptor
  • the method further WSGR Docket No.50401-795.601 comprises administering to the subject a cell comprising a chimeric antigen receptor (CAR) or a recombinant nucleic acid encoding the CAR.
  • CAR chimeric antigen receptor
  • the multiepitopic polypeptide comprising a RAS polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide administered in the subject can elicit specific T cell responses of the T cells expressing TCRs that can recognize RAS epitopes in complex with MHC molecules.
  • the multiepitopic polypeptide having different RAS epitopes can elicit enhanced T cell responses compared to the full-length RAS polypeptide.
  • the multiepitopic polypeptide comprising a RAS polypeptide comprising a different RAS epitopes (or the recombinant nucleic acid encoding the RAS polypeptide) administered in a subject can lead to increased cytokine release by the RAS specific T cells of at least 1.1 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 5.5 times, 6 times, 6.5 times, 7 times, 7.5 times, 8 times, 8.5 times, 9 times, 9.5 times, 10 times, 20 times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times, or 100 times more compared to that in a subject administered with the full-length RAS polypeptide or a recombinant nucleic acid encoding the full
  • APCs having (e.g., transfected or otherwise delivered with) the multiepitopic polypeptide comprising a RAS polypeptide comprising different RAS epitopes (or the recombinant nucleic acid encoding the RAS polypeptide) can lead to increased cytokine release by the RAS specific T cells of at least 1.1 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 5.5 times, 6 times, 6.5 times, 7 times, 7.5 times, 8 times, 8.5 times, 9 times, 9.5 times, 10 times, 20 times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times, or 100 times more compared to APCs having the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide.
  • Cytokine release can be measured using a cytometric bead assay, ELISA, or any other suitable method of quantifying levels of cytokine release.
  • the first RAS epitope sequence and the second RAS epitope sequence is separated by a linker.
  • the first RAS amino acid sequence is the first epitope sequence.
  • the second RAS amino acid sequence is the second epitope sequence.
  • the first RAS amino acid sequence is the first epitope sequence and the second RAS amino acid sequence is the second epitope sequence.
  • the first RAS amino acid sequence consists of the first epitope sequence.
  • the second the second RAS amino acid sequence consists of the second epitope sequence.
  • the first RAS amino acid sequence consists of the first epitope sequence and the second the second RAS amino acid sequence consists of the second epitope sequence. [0479] In some embodiments, each different RAS epitope sequence is separated by a linker. [0480] In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation. In some embodiments, the second RAS amino acid sequence comprises a second RAS mutation. In some WSGR Docket No.50401-795.601 embodiments, the second RAS mutation is different from the first RAS mutation. In some embodiments, the second RAS mutation is same as the first RAS mutation.
  • the first RAS amino acid sequence comprises a first RAS mutation
  • the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation.
  • the first RAS amino acid sequence comprises a first RAS mutation
  • the second RAS amino acid sequence comprises a second RAS mutation same as the first RAS mutation.
  • the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C.
  • the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C.
  • the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell.
  • the first RAS mutation is G12V, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72. In some embodiments, the first RAS mutation is G12D, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79. In some embodiments, the first RAS mutation is G12C, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096.
  • the first RAS epitope sequence first RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide.
  • the second RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide.
  • the first RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide.
  • the second RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide.
  • the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker.
  • the first RAS amino acid sequence comprises the first RAS epitope sequence and one, two, three, four, five or more residues flanking the N-terminus or C-terminus of the first RAS epitope sequence from the full length RAS polypeptide.
  • the second RAS amino acid sequence comprises the second RAS epitope sequence and one, two, three, four, five or more residues flanking the N-terminus or C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide.
  • the multiepitopic polypeptide does not comprise more than 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more consecutive amino acids from the full-length RAS polypeptide.
  • WSGR Docket No.50401-795.601 In some embodiments, the multiepitopic polypeptide does not comprise more than 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more consecutive amino acids from the full-length RAS polypeptide.
  • the TCR recognizes and binds to a peptide:MHC complex.
  • the peptide:MHC complex comprises the first RAS epitope sequence and a human MHC encoded by an HLA allele.
  • the TCR recognizes and binds to a peptide:MHC complex.
  • the peptide:MHC complex comprises the second RAS epitope sequence and a human MHC encoded by an HLA allele.
  • Also provided herein is a method of treating a subject with a disease or condition.
  • the disease or condition can comprise cancer.
  • the method comprises administering to the subject a RAS polypeptide.
  • the method comprises administering to the subject a recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the method comprises administering to the subject a cell comprising the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the RAS polypeptide comprises a RAS epitope sequence. In some embodiments, the subject has been previously administered a T-cell receptor (TCR). In some embodiments, the subject has been previously administered a recombinant nucleic acid encoding the TCR or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR.
  • TCR T-cell receptor
  • the TCR recognizes and binds to a peptide:MHC complex.
  • the peptide:MHC complex comprises the RAS epitope sequence.
  • the peptide:MHC complex comprises a human MHC encoded by an HLA allele.
  • the peptide:MHC complex comprises (i) the RAS epitope sequence and (ii) a human MHC encoded by an HLA allele.
  • a method of treating a subject with a disease or condition can comprise a cancer.
  • the method comprises administering to the subject a T-cell receptor (TCR).
  • TCR T-cell receptor
  • the method comprises administering to the subject a recombinant nucleic acid encoding the TCR. In some embodiments, the method can comprise administering to the subject an immune cell comprising the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the TCR recognizes and binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence. In some embodiments, the peptide:MHC complex comprises a human MHC encoded by an HLA allele.
  • the peptide:MHC complex comprises (i) a RAS epitope sequence and (ii) a human MHC encoded by an HLA allele.
  • the subject has been previously administered a RAS polypeptide.
  • the subject has been previously administered a recombinant nucleic acid encoding the RAS polypeptide.
  • the RAS polypeptide comprises the RAS epitope sequence.
  • WSGR Docket No.50401-795.601 [0489] Also provided herein is a method of treating a subject with a disease or condition.
  • the disease or condition can comprise a cancer.
  • the method comprises administering to the subject a RAS polypeptide.
  • the method comprises administering to the subject a recombinant nucleic acid encoding the RAS polypeptide.
  • the RAS polypeptide comprises a RAS epitope sequence.
  • the method comprises administering the subject a TCR or an immune cell comprising the TCR.
  • the method comprises administering to the subject a recombinant nucleic acid encoding the TCR or an immune cell comprising the TCR or the recombinant nucleic acid encoding the TCR.
  • the TCR recognizes and binds to a peptide:MHC complex.
  • the peptide:MHC complex comprises a RAS epitope sequence.
  • the peptide:MHC complex comprises a human MHC encoded by an HLA allele. In some embodiments, the peptide:MHC complex comprises (i) a RAS epitope sequence and (ii) a human MHC encoded by an HLA allele. In some embodiments, the method comprises administering to the subject the RAS polypeptide concurrently with the TCR or an immune cell comprising the TCR. In some embodiments, the method comprises administering to the subject the RAS polypeptide concurrently with the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the method comprises administering to the subject the recombinant nucleic acid encoding the RAS polypeptide concurrently with the TCR or an immune cell comprising the TCR. In some embodiments, the method comprises administering to the subject the recombinant nucleic acid encoding the RAS polypeptide concurrently with the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the method comprises administering to the subject the RAS polypeptide prior to the TCR or an immune cell comprising the TCR.
  • the method comprises administering to the subject the RAS polypeptide prior to the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the method comprises administering to the subject the recombinant nucleic acid encoding the RAS polypeptide prior to the TCR or an immune cell comprising the TCR. In some embodiments, the method comprises administering to the subject the recombinant nucleic acid encoding the RAS polypeptide prior to the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the method comprises administering to the subject the RAS polypeptide subsequent to the TCR or an immune cell comprising the TCR. In some embodiments, the method comprises administering to the subject the RAS polypeptide subsequent to the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the method comprises administering to the subject the recombinant WSGR Docket No.50401-795.601 nucleic acid encoding the RAS polypeptide subsequent to the TCR or an immune cell comprising the TCR.
  • the method comprises administering to the subject the recombinant nucleic acid encoding the RAS polypeptide subsequent to the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the TCR described herein can be a soluble TCR.
  • the TCR described herein can be a membrane-bound TCR.
  • the TCR described herein can be expressed by an immune cell.
  • the method comprises administering a cell comprising the RAS polypeptide or nucleic acid encoding the RAS polypeptide concurrently with administering to the subject a TCR, a recombinant nucleic acid encoding the TCR or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS peptide sequence, and (ii) a human MHC encoded by an HLA allele.
  • the method comprises administering a cell comprising the RAS polypeptide or nucleic acid encoding the RAS polypeptide subsequent to administering to the subject a TCR, a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS peptide sequence, and (ii) a human MHC encoded by an HLA allele.
  • the method comprises administering a cell comprising the RAS polypeptide or nucleic acid encoding the RAS polypeptide prior to administering to the subject a TCR, a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS peptide sequence, and (ii) a human MHC encoded by an HLA allele.
  • the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more after the subject has been administered the TCR or the recombinant nucleic acid encoding the TCR.
  • the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more after the subject has been administered an immune cell comprising the TCR or the recombinant nucleic acid encoding the TCR.
  • the TCR or the recombinant nucleic acid encoding the TCR can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, WSGR Docket No.50401-795.601 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more after the subject has been administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide.
  • the immune cell comprising the TCR or the recombinant nucleic acid encoding the TCR can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more after the subject has been administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide.
  • the RAS polypeptide is administered at least 1 hour after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 2 hours after the subject has been administered the TCR or an immune cell comprising the TCR or an immune cell comprising the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 4 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 8 hours after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the RAS polypeptide is administered at least 12 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 1 day after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 2 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 5 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 10 days after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the RAS polypeptide is administered at least 20 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 30 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 1 month after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 2 months after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 3 months after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the RAS polypeptide is administered at least 6 months after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the RAS polypeptide is administered at least 1 year after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the RAS polypeptide is administered at least 2 years after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the RAS polypeptide is administered at least 3 years or more after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 hour after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 4 hours after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 8 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 12 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 day after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 5 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 10 days after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 20 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 30 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 month after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 months after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 3 months after the subject has been administered the TCR or an immune cell comprising the TCR. In some WSGR Docket No.50401-795.601 embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 6 months after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 year after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 years after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 3 years or more after the subject has been administered the TCR or an immune cell comprising the TCR.
  • the RAS polypeptide is administered at least 1 hour after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 2 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 4 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the RAS polypeptide is administered at least 8 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 12 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 1 day after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the RAS polypeptide is administered at least 2 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 5 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 10 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the RAS polypeptide is administered at least 20 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 30 days after the subject has been WSGR Docket No.50401-795.601 administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the RAS polypeptide is administered at least 1 month after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 2 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 3 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the RAS polypeptide is administered at least 6 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 1 year after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 2 years after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the RAS polypeptide is administered at least 3 years or more after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 hour after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 4 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 8 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 12 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the recombinant nucleic acid WSGR Docket No.50401-795.601 encoding the RAS polypeptide is administered at least 1 day after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 5 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 10 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 20 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 30 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 month after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 3 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 6 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 year after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 years after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the recombinant nucleic acid encoding the RAS WSGR Docket No.50401-795.601 polypeptide is administered at least 3 years or more after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR.
  • the TCR or an immune cell comprising the TCR is administered at least 1 hour after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 hours after the subject has been administered the RAS polypeptide.
  • the TCR or an immune cell comprising the TCR is administered at least 4 hours after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 8 hours after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 12 hours after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 day after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 days after the subject has been administered the RAS polypeptide.
  • the TCR or an immune cell comprising the TCR is administered at least 5 days after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 10 days after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 20 days after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 30 days after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 month after the subject has been administered the RAS polypeptide.
  • the TCR or an immune cell comprising the TCR is administered at least 2 months after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 3 months after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 6 months after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 year after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 years after the subject has been administered the RAS polypeptide.
  • the TCR or an immune cell comprising the TCR is administered at least 3 years or more after the subject has been administered the RAS polypeptide.
  • WSGR Docket No.50401-795.601 [0498]
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 hour after the subject has been administered the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 hours after the subject has been administered the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 4 hours after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 8 hours after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 12 hours after the subject has been administered the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 day after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 days after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 5 days after the subject has been administered the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 10 days after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 20 days after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 30 days after the subject has been administered the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 month after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 months after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 3 months after the subject has been administered the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an WSGR Docket No.50401-795.601 immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 6 months after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 year after the subject has been administered the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 years after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 3 years or more after the subject has been administered the RAS polypeptide. [0499] In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 hour after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the TCR or an immune cell comprising the TCR is administered at least 2 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 4 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 8 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the TCR or an immune cell comprising the TCR is administered at least 12 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 day after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the TCR or an immune cell comprising the TCR is administered at least 5 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 10 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 20 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the TCR or an immune cell comprising the TCR is administered at least 30 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 month after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some WSGR Docket No.50401-795.601 embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the TCR or an immune cell comprising the TCR is administered at least 3 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 6 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 year after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the TCR or an immune cell comprising the TCR is administered at least 2 years after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 3 years or more after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. [0500] In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 hour after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 4 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 8 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 12 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 day after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 5 days after the subject has WSGR Docket No.50401-795.601 been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 10 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic encoding the TCR is administered at least 20 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 30 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 month after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 3 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 6 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 year after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 years after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 3 years or more after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide.
  • the TCR is expressed by a cell.
  • the cell is an immune cell.
  • the recombinant nucleic acid encoding the TCR is expressed by a cell.
  • the cell is an immune cell.
  • the TCR is a soluble TCR.
  • the method comprises administering two or more different TCRs. In some embodiments, the method comprises administering two or more recombinant nucleic acids encoding the two or more different TCRs. In some embodiments, the two or more TCRs comprise a first TCR and a second TCR. In some embodiments, the two or more different TCRs are expressed on the surface of two different immune cells. In some embodiments, the first TCR and the second TCR bind to different peptide:MHC complexes, each peptide:MHC complex comprising (i) an epitope sequence and (ii) a human MHC encoded by an HLA allele.
  • the two or more different TCRs are administered separately or co-administered in a same mixture.
  • recombinant nucleic acids encoding the two or more different TCRs are administered separately or co-administered in a same mixture.
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12V mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05
  • the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12D mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA- C*05:01, HLA-A*-3:01, HLA
  • the TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12V mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05
  • the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12C mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA- A*68:01, and HLA-C*03:03.
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12D mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01.
  • the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12C mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA- A*68:01, and HLA-C*03:03.
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05 and the second TCR binds to a peptide:MHC WSGR Docket No.50401-795.601 complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75- 79 and an MHC encoded by an HLA allele selected from the group consisting of HLA-B
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01 and, HLA-A*03 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75-79 and an MHC encoded by an HLA allele selected from the group consisting of HLA- B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA- A*68:01 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03.
  • the RAS polypeptide does not comprise a full-length RAS protein sequence.
  • the RAS polypeptide comprises a RAS epitope sequence.
  • the RAS epitope sequence comprises a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NOs: 58 or 59.
  • the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NOs: 58 or 59.
  • the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NOs: 58 or 59. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 59. In some cases, the HLA allele is an HLA-A allele. In some cases, the HLA allele is selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*03:02, HLA-A*03:05, HLA-B*40:01, and HLA-A*68:01.
  • the RAS epitope sequence comprises a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 60.
  • the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 60.
  • the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO 60.
  • the RAS epitope sequence comprises a WSGR Docket No.50401-795.601 sequence of SEQ ID NO: 60.
  • the HLA allele is an HLA-C allele. In some embodiments, the HLA allele is an HLA-C*01:02 allele.
  • the RAS epitope sequence comprises a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NOs: 61 or 62. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NOs: 61 or 62.
  • the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NOs: 61 or 62. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 61 or 62. In some embodiments, the HLA allele is an HLA-C allele. In some embodiments, the HLA allele is an HLA-C*03:03, or HLA-C*03:04. [0507] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NOs: 58 or 59.
  • the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NOs: 58 or 59. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NOs: 58 or 59. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 59. In some embodiments, the HLA allele is an HLA-A allele. In some embodiments, the HLA allele is an HLA-A*11:01.
  • the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 65-71. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 65-71. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 65-71. In some embodiments, the RAS epitope sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 65-71. In some embodiments, the HLA allele is an HLA-DRB1 allele.
  • the HLA allele is an HLA-DRB1*07:01.
  • the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NOs: 58 or 72. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NOs: 58 or 72. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NOs: 58 or 72. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 72. In some embodiments, the HLA allele is an HLA-A allele.
  • the HLA allele is selected from the group consisting of A*03:01, HLA-A*03:02, and HLA-A*03:05.
  • WSGR Docket No.50401-795.601 [0510]
  • the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 75. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 75. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 75. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 75.
  • the HLA allele is an HLA-B allele. In some embodiments, the HLA allele is an HLA-B*07:02. In some embodiments, the HLA allele is an HLA- C allele. In some embodiments, the HLA allele is selected from the group consisting of HLA- C*08:02, HLA-C*03:04, and HLA-C*05:01. [0511] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 76. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 76.
  • the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 76. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 76. In some embodiments, the HLA allele is an HLA-A allele. In some embodiments, the HLA allele is selected from the group consisting of HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01. [0512] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 77.
  • the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 77. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 77. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 77. In some embodiments, the HLA allele is an HLA-A allele. In some embodiments, the HLA allele is HLA-A*11:01. [0513] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NOs: 78 or 79.
  • the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NOs: 78 or 79. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NOs: 78 or 79. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 78 or 79. In some embodiments, the HLA allele is an HLA-C allele. In some embodiments, the HLA allele is HLA-C*08:02. [0514] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 29.
  • the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to WSGR Docket No.50401-795.601 a sequence of SEQ ID NO: 29. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 29. In some embodiments, the HLA allele is an HLA-DRB1 allele. In some embodiments, the HLA allele is HLA-DRB1*11:01. [0515] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 81.
  • the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 81. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 81. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 81. In some embodiments, the HLA allele is an HLA-A allele. In some embodiments, the HLA allele is selected from a group consisting of HLA-A*3:01, HLA-A*11:01, and HLA-A*68:01.
  • the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 1096. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 1096. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 1096. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 1096. In some embodiments, the HLA allele is an HLA-A allele.
  • the HLA allele is selected from a group consisting of HLA- A*3:01, HLA-A*11:01, and HLA-A*68:01.
  • the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 82. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 82. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 82. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 82.
  • the HLA allele is an HLA-C allele. In some embodiments, the HLA allele is HLA-C*03:03. [0518]
  • the RAS polypeptide comprises a multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise a full-length RAS polypeptide. In some embodiments, the sequence of the multiepitopic polypeptide is the same RAS epitope sequence. In some embodiments, the multiepitopic polypeptide comprises two or more different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 2 different RAS epitope sequences.
  • the multiepitopic polypeptide comprises at least 3 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 4 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 5 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide WSGR Docket No.50401-795.601 comprises at least 6 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 8 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 9 different RAS epitope sequences.
  • the multiepitopic polypeptide comprises at least 10 or more different RAS epitope sequences. In some embodiments, the different RAS epitope sequences are separated. In some embodiments, the different RAS epitope sequences are separated by linker sequences. In some embodiments, the RAS polypeptide is a multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide is a RAS polypeptide. [0519] In some embodiments, antigen presenting cells (APCs) of subject administered the RAS polypeptide present a RAS epitope sequence as a peptide:MHC complex.
  • APCs antigen presenting cells
  • antigen presenting cells of subject administered the nucleic acid encoding the RAS polypeptide comprising the multiepitopic polypeptide present a RAS epitope sequence as a peptide:MHC complex.
  • the APCs present more of a RAS epitope as a peptide:MHC complex compared to the APCs of a subject administered a full length RAS polypeptide or recombinant nucleic acid encoding the full-length RAS polypeptide.
  • T cells of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide exhibit increased expansion compared to T cells of a subject administered a full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide.
  • the multiepitopic polypeptide comprises a first RAS amino acid sequence comprising a first RAS epitope sequence.
  • the multiepitopic polypeptide comprises a second RAS amino acid sequence comprising a second RAS epitope sequence.
  • the first RAS epitope sequence and the second RAS epitope sequence are different. In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence is separated by a linker.
  • the first amino acid sequence is the first epitope sequence. In some embodiments the second amino acid sequence is the second epitope sequence. In some embodiments, the first amino acid sequence is the first epitope sequence, and the second amino acid sequence is the second epitope sequence. In some embodiments, the first amino acid sequence consists of the first epitope sequence. In some embodiments, the second amino acid sequence consists of the second epitope sequence.
  • the first amino acid sequence consists of the first epitope sequence
  • the second amino acid sequence consists of the second epitope sequence.
  • the first RAS amino acid sequence comprises a first RAS mutation.
  • the second RAS amino acid sequence comprises a second RAS mutation.
  • the first RAS mutation is different from the second RAS mutation.
  • the first RAS amino acid sequence comprises a first RAS mutation
  • the second RAS amino acid sequence comprises a second RAS mutation.
  • the first RAS amino acid sequence comprises a first RAS mutation
  • the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation.
  • the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C.
  • the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C.
  • the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell.
  • the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell.
  • the first RAS mutation is G12V, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72.
  • the first RAS mutation is G12D, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79. In some embodiments, the first RAS mutation is G12C, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096. [0525] In some embodiments, the first RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide.
  • the second RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide.
  • the first RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide.
  • the second RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide.
  • the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker.
  • the first amino acid sequence comprises the first RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first RAS epitope sequence from the full length RAS polypeptide.
  • the second amino acid sequence comprises the second RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second RAS epitope sequence from the full length RAS polypeptide.
  • the multiepitopic polypeptide does not comprise more than 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more consecutive amino acids from the full-length RAS polypeptide.
  • the multiepitopic polypeptide comprises a first RAS epitope sequence.
  • the first RAS epitope sequence is operably linked to a second RAS epitope sequence.
  • the first RAS epitope sequence and the second RAS epitope sequence are the same.
  • the first RAS epitope sequence and second RAS epitope sequence are different.
  • the first RAS epitope sequence and second RAS epitope sequence are presentable by different HLA alleles. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are presented by different HLA alleles. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are predicted to bind to different HLA alleles. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are predicted to be presented by different HLA alleles. [0530] In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 500nM.
  • a first RAS epitope sequence binds to a first HLA allele with a KD less than 400nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 300nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele. In some embodiments, a first RAS epitope sequence is predicted to bind to a first HLA allele. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 200nM.
  • a first RAS epitope sequence binds to a first HLA allele with a KD less than 100nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 50nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 1nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele. In some embodiments, a first RAS epitope sequence is predicted to bind to a second HLA allele.
  • a first RAS epitope sequence binds to a second HLA allele with a KD of more than 200nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 300nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 500nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 600nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 700nM.
  • a first RAS epitope sequence binds to a second HLA allele with a KD of more than 800nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 900nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 1000nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 1nM and binds to second HLA allele with WSGR Docket No.50401-795.601 a KD of more than 200nM.
  • a first RAS epitope sequence binds to a first HLA allele with a KD of less than 50nM and binds to second HLA allele with a KD of more than 300nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 100nM and binds to second HLA allele with a KD of more than 500nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 200 nM and binds to second HLA allele with a KD of more than 600nM.
  • the first RAS epitope sequence is operably linked to the second RAS epitope sequence. In some aspects, the first RAS epitope sequence is operably linked to the second RAS epitope sequence via a linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0532] In some embodiments, the multiepitopic polypeptide comprises a first RAS epitope sequence, operably linked to a second RAS epitope sequence, operably linked to a third RAS epitope sequence.
  • the multiepitopic polypeptide comprises a first amino acid sequence comprising a first RAS epitope sequence, operably linked to a second amino acid sequence comprising a second RAS epitope sequence, operably linked to a third amino acid sequence comprising a third RAS epitope sequence.
  • the first RAS epitope sequence, the second RAS epitope sequence, or the third RAS epitope sequence comprises a RAS mutation selected from the group consisting of G12V, G12D, and G12C.
  • the first RAS epitope sequence, the second RAS epitope sequence, and the third RAS epitope sequence comprises a RAS mutation selected from the group consisting of G12V, G12D, and G12C. In some embodiments, the first RAS epitope sequence, the second RAS epitope sequence, and the third RAS epitope sequence comprise different RAS mutations. In some embodiments, the first RAS epitope sequence comprises a G12V mutation. In some embodiments, the first RAS epitope sequence comprises a G12D mutation. In some embodiments, the first RAS epitope sequence comprises a G12C mutation. In some embodiments, the second RAS epitope sequence comprises a G12V mutation.
  • the second RAS epitope sequence comprises a G12D mutation. In some embodiments, the second RAS epitope sequence comprises a G12C mutation. In some embodiments, the third RAS epitope sequence comprises a G12V mutation. In some embodiments, the third RAS epitope sequence comprises a G12D mutation. In some embodiments, the third RAS epitope sequence comprises a G12C mutation.
  • the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05.
  • the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA- C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05.
  • the first RAS epitope sequence binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA- A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA- A*03:02, and HLA-A*03:05.
  • the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA- A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA- C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05.
  • HLA- A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA- C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05 HLA- A*11:01, HLA-A*03
  • the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05.
  • the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA- C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02.
  • the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02.
  • the second RAS epitope sequence binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02.
  • the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA- C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02.
  • the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA- C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02.
  • the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03.
  • the third RAS epitope WSGR Docket No.50401-795.601 sequence is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03.
  • the third RAS epitope sequence binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03.
  • the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03.
  • the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03.
  • the subject does not express an HLA that binds to each RAS epitope of the multiepitopic polypeptide. In some cases, the subject only expresses HLA alleles that bind to a subset of RAS epitope sequences of the multiepitopic polypeptide.
  • the RAS polypeptide comprises a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27- 29.
  • the RAS polypeptide comprises a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises a sequence with at least 90% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 27- 29.
  • the RAS polypeptide comprises a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises a sequence with at least 70% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises a sequence with at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises a sequence selected from the group consisting of SEQ ID NOs: 27-29. WSGR Docket No.50401-795.601 [0540] In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises one or more copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 70% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27- 29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence selected from the group consisting of SEQ ID NOs: 27-29. [0542] In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises two copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of one or more sequences with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises two copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 70% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 80% sequence identity to each sequence of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises two copies of one or more sequences with at least 90% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of each sequence of SEQ ID NOs: 27-29. [0544] In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises three copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of one or more sequences with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises three copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 70% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 80% sequence identity to each sequence of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises three copies of one or more sequences with at least 90% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of each sequence of SEQ ID NOs: 27-29. [0546] In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises four copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least WSGR Docket No.50401-795.601 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of one or more sequences with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises four copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0547] In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 70% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 80% sequence identity to each sequence of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises four copies of one or more sequences with at least 90% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of each sequence of SEQ ID NOs: 27-29. [0548] In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises five copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of one or more sequences with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises five copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 70% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 80% sequence identity to each sequence of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises five copies of one or more sequences with at least 90% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of each sequence of SEQ ID NOs: 27-29.
  • WSGR Docket No.50401-795.601 [0550] In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises six or more copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of one or more sequences with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises six or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 70% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 80% sequence identity to each sequence of SEQ ID NOs: 27- 29.
  • the RAS polypeptide comprises six or more copies of one or more sequences with at least 90% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of each sequence of SEQ ID NOs: 27-29.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28.
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 28.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a WSGR Docket No.50401-795.601 sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 29 via a linker, and the sequence of SEQ ID NO: 29 operably linked to the sequence of SEQ ID NO: 28 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO:
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 operably linked to the sequence of SEQ ID NO: 27 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29.
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 29.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO:
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 operably linked to the sequence of SEQ ID NO: 29 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence WSGR Docket No.50401-795.601 having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31.
  • the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29.
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 29.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO:
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 operably linked to the sequence of SEQ ID NO: 29 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence WSGR Docket No.50401-795.601 identity to a sequence of SEQ ID NO: 112.
  • the linker comprises a sequence of SEQ ID NO: 112.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO:
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 29 via a linker, and the sequence of SEQ ID NO: 29 operably linked to the sequence of SEQ ID NO: 27 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably WSGR Docket No.50401-795.601 linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28.
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 28.
  • the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO:
  • the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 operably linked to the sequence of SEQ ID NO: 28 via a linker.
  • the linker is a cleavable linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31.
  • the linker comprises a sequence of SEQ ID NO: 31.
  • the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112.
  • the RAS polypeptide comprises at least two copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, and operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises at least two copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises three copies of the multiepitopic polypeptide.
  • the RAS polypeptide comprises five copies of the multiepitopic polypeptide.
  • the RAS polypeptide comprises at three copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, and operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises at three copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises at four copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, and operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises at four copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises at five copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at WSGR Docket No.50401-795.601 least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, and operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27.
  • the RAS polypeptide comprises at five copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27.
  • the RAS polypeptide further comprises a secretory domain (Sec) sequence.
  • the Sec sequence is at the N terminus of the multiepitopic polypeptide.
  • the Sec comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 32.
  • the Sec sequence comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 32.
  • the Sec sequence comprises a sequence of SEQ ID NO: 32. [0569] In some cases, the Sec sequence is operably linked to the multiepitopic polypeptide. In some embodiments, the Sec sequence is operably linked to the multiepitopic polypeptide via a linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 30. In some embodiments, the linker comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 30. In some cases, the linker comprises a sequence of SEQ ID NO: 30. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31.
  • the linker comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 31. In some cases, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 112. In some cases, the linker comprises a sequence of SEQ ID NO: 112.
  • the RAS polypeptide further comprises an MHC Class I trafficking domain (MITD) sequence.
  • the MITD sequence is at the C terminus of the multiepitopic polypeptide.
  • the MITD sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 33.
  • the MITD sequence comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: WSGR Docket No.50401-795.601 33.
  • the Sec sequence comprises a sequence of SEQ ID NO: 33.
  • the multiepitopic polypeptide is operably linked to the MITD sequence via a linker.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 30.
  • the linker comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 30.
  • the linker comprises a sequence of SEQ ID NO: 30In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0571] In some embodiments, the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to sequence identity to a sequence of SEQ ID NO: 25.
  • the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to sequence identity to a sequence of SEQ ID NO: 26. In some embodiments, the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to sequence identity to a sequence of SEQ ID NO: 113.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 14.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 14.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 15.
  • the WSGR Docket No.50401-795.601 recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 16.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 16.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 17.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 17.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 18.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence WSGR Docket No.50401-795.601 having at least 60% sequence identity to a sequence of SEQ ID NO: 18.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 18.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 18.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 19.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 19.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 20.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 20.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 21.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 21.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 21.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 21.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences with at least 90% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 9. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 14.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 18.
  • the recombinant nucleic WSGR Docket No.50401-795.601 acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 21.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 22. [0582] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 14.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 19.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100- 102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 16.
  • the recombinant nucleic acid encoding the RAS WSGR Docket No.50401-795.601 polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 17.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 19.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 21.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences with at least 90% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104- 106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 16.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 19.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ WSGR Docket No.50401-795.601 ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14- 23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 19.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 20.
  • the recombinant nucleic acid WSGR Docket No.50401-795.601 encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 22. [0587] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 18.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 20.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 22. WSGR Docket No.50401-795.601 [0589] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 18.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 15.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 20.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 22.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of WSGR Docket No.50401-795.601 SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence a having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence of any one of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs:
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% WSGR Docket No.50401-795.601 sequence identity to any one of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 operably linked to a sequence of any one of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence.
  • the linker sequence encodes a cleavable linker.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13.
  • the linker sequence comprises a sequence of SEQ ID NO: 8.
  • the linker sequence comprises a sequence of SEQ ID NO: 5.
  • the linker sequence comprises a sequence of SEQ ID NO: 6.
  • the linker sequence comprises a sequence of SEQ ID NO: 8.
  • the linker sequence comprises a sequence of SEQ ID NO: 9.
  • the linker sequence comprises a sequence of SEQ ID NO: 10.
  • the linker sequence comprises a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 13. WSGR Docket No.50401-795.601 [0598] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19,
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14- 16, 84, 92, 96, 100, 104, and 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence of any one of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs:
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence WSGR Docket No.50401-795.601 identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence.
  • the linker sequence encodes a cleavable linker.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 9.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 60%, at WSGR Docket No.50401-795.601 least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%,
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence of any one of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence and the sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence and the sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence and the sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence of any one of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence.
  • the linker sequence encodes a cleavable linker.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 9.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12.
  • the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises at least two copies of a string of sequences.
  • each string of sequences comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, WSGR Docket No.50401-795.601 at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20
  • each string of sequences comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108.
  • each string of sequences comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence of any one of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of the string of sequences.
  • the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises seven copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises eight copies of the string of sequences.
  • the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a secretory (Sec) sequence.
  • the Sec sequence is at the 5’ end of the string of sequences.
  • the Sec sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 3.
  • the string of sequences is operably linked to the Sec sequence.
  • the string of sequences is operably linked to the Sec sequence via a linker sequence.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 4. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 7. In some embodiments, the linker comprises a sequence of SEQ ID NO: 4. In some embodiments, the linker comprises a sequence of SEQ ID NO: 7.
  • the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MHC I Trafficking Domain (MITD) sequence.
  • the sequence encoding an MITD sequence is at the 3’ end of the string of sequences.
  • the MITD sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 24 or 90.
  • the string of sequences is operably linked to the MITD sequence.
  • the string of sequences is operably linked to the MITD sequence via a linker sequence.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 4.
  • the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 7.
  • the linker comprises a sequence of SEQ ID NO: 4.
  • the linker comprises a sequence of SEQ ID NO: 7.
  • the recombinant nucleic acid is codon optimized. In some embodiments, the recombinant nucleic acid is not codon optimized. In some embodiments, the recombinant nucleic acid is DNA. In some embodiments, the recombinant nucleic acid is RNA. In some embodiments the recombinant nucleic acid is mRNA.
  • the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 1.
  • the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 2.
  • the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 95.
  • the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 103.
  • the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at WSGR Docket No.50401-795.601 least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 111.
  • the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 95. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 99.
  • the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 103. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 111. [0619] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 2.
  • the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 95. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 103.
  • the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 111. [0620] In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 95.
  • the recombinant nucleic acid comprises a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 103. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 111. WSGR Docket No.50401-795.601 [0621] In some embodiments, the subject expresses more of the RAS epitope when administered with the codon optimized recombinant nucleic acid than administered with wild-type recombinant nucleic acid.
  • the TCR comprises a beta chain construct. In some embodiments, the TCR comprises an alpha chain construct. In some embodiments, the TCR comprises a beta chain construct and an alpha chain construct. In some embodiments, the TCR beta chain construct comprises a complementarity determining region 3 (CDR3). In some embodiments the TCR beta chain construct comprises a CDR3 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 57. In some embodiments the TCR beta chain construct comprises a CDR3 having an amino acid sequence set forth in SEQ ID NO: 57. In some embodiments, the TCR beta chain construct comprises a variable region.
  • CDR3 complementarity determining region 3
  • the TCR beta chain construct comprises a variable region having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 52 or SEQ ID NO: 53. In some embodiments, the TCR beta chain construct comprises a CDR1. In some embodiments, the TCR beta chain construct comprises a CDR1 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 55. In some embodiments, the TCR beta chain construct comprises a CDR1 having an amino acid set forth in SEQ ID NO: 55. In some embodiments, the TCR beta chain construct comprises a CDR2.
  • the TCR beta chain construct comprises a CDR2 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 56. In some embodiments, the TCR beta chain construct comprises a CDR2 having an amino acid sequence set forth in SEQ ID NO: 56. [0623] In some embodiments, the TCR comprises an alpha chain construct. In some embodiments, the alpha chain construct comprises a CDR1. In some embodiments, the alpha chain construct comprises a CDR2. In some embodiments, the alpha chain construct comprises a CDR3.
  • the alpha chain construct comprises a CDR1 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 46. In some embodiments, the alpha chain construct comprises a CDR1 having an amino acid sequence set forth in SEQ ID NO: 46. In some embodiments, the alpha chain construct comprises a CDR2 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 47. In some embodiments, the alpha chain construct comprises a CDR2 having an amino acid sequence set forth in SEQ ID NO: 47.
  • the alpha chain construct comprises a CDR3 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 100. In some embodiments, the alpha chain construct comprises a CDR3 having an amino acid WSGR Docket No.50401-795.601 sequence set forth in SEQ ID NO: 48. In some embodiments, the alpha chain construct comprises a variable region. In some embodiments the alpha chain construct comprises a variable region having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44.
  • the alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44.
  • the TCR comprises a beta chain having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 49 or SEQ ID NO: 51.
  • the TCR comprises a beta chain having an amino acid sequence set forth in SEQ ID NO: 49 or SEQ ID NO: 51.
  • the TCR comprises an alpha chain having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 40 or SEQ ID NO: 42.
  • the TCR comprises an alpha chain having an amino acid sequence set forth in SEQ ID NO: 40 or SEQ ID NO: 42. [0625] In some embodiments, the TCR comprises a beta chain construct. In some embodiments, the TCR comprises an alpha chain construct. In some embodiments, the TCR comprises a beta chain construct and an alpha chain construct. In some embodiments, the TCR beta chain construct comprises a complementarity determining region 3 (CDR3). In some embodiments the TCR beta chain construct comprises a CDR3 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one of TCR beta chain CDR3 presented in Tables 8A-8D.
  • CDR3 complementarity determining region 3
  • the TCR beta chain construct comprises a CDR3 having an amino acid sequence of any one TCR beta chain CDR3 presented in Tables 8A-8D. In some embodiments, the TCR beta chain construct comprises a variable region. In some embodiments the TCR beta chain construct comprises a variable region having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR beta variable domain presented in Tables 8A-8D. In some embodiments, the TCR beta chain construct comprises a CDR1. In some embodiments, the TCR beta chain construct comprises a CDR1 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR beta chain CDR1 presented in Tables 8A-8D.
  • the TCR beta chain construct comprises a CDR1 having an amino acid sequence of any one TCR beta chain CDR1 presented in Tables 8A-8D. In some embodiments, the TCR beta chain construct comprises a CDR2. In some embodiments, the TCR beta chain construct comprises a CDR2 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence any one TCR beta chain CDR2 presented in Tables 8A-8D. In some embodiments, the TCR beta chain WSGR Docket No.50401-795.601 construct comprises a CDR2 having an amino acid sequence of any one TCR beta chain CDR2 presented in Tables 8A-8D. [0626] In some embodiments, the TCR comprises an alpha chain construct.
  • the alpha chain construct comprises a CDR1. In some embodiments, the alpha chain construct comprises a CDR2. In some embodiments, the alpha chain construct comprises a CDR3. In some embodiments, the alpha chain construct comprises a CDR1 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR alpha chain CDR1 presented in Tables 8A-8D. In some embodiments, the alpha chain construct comprises a CDR1 having an amino acid sequence of any one TCR alpha chain CDR1 presented in Tables 8A- 8D.
  • the alpha chain construct comprises a CDR2 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR alpha chain CDR2 presented in Tables 8A-8D. In some embodiments, the alpha chain construct comprises a CDR2 having an amino acid sequence of any one TCR alpha chain CDR2 presented in Tables 8A-8D. In some embodiments, the alpha chain construct comprises a CDR3 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR alpha chain CDR3 presented in Tables 8A-8D.
  • the alpha chain construct comprises a CDR3 having an amino acid sequence of any one TCR alpha chain CDR3 presented in Tables 8A-8D. In some embodiments, the alpha chain construct comprises a variable region. In some embodiments the alpha chain construct comprises a variable region having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR alpha variable domain presented in Tables 8A-8D. In some embodiments the alpha chain construct comprises a variable region having an amino acid sequence of any one TCR alpha variable domain presented in Tables 8A-8D.
  • the TCR comprises a beta chain having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR beta chain presented in Tables 8A-8D. In some embodiments, the TCR comprises a beta chain having an amino acid sequence of any one TCR beta chain presented in Tables 8A-8D. In some embodiments, the TCR comprises an alpha chain having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR alpha chain presented in Tables 8A-8D. In some embodiments, the TCR comprises an alpha chain having an amino acid sequence of any one TCR alpha chain presented in Tables 8A-8D. [0628] Table 8A.
  • the disease or condition is a cancer.
  • the method comprises administering to the subject a therapy.
  • the therapy comprises a multiepitopic polypeptide.
  • the therapy comprises a recombinant nucleic acid encoding the multiepitopic polypeptide.
  • the therapy comprises a cell comprising the multiepitopic polypeptide.
  • the therapy comprises a cell comprising the recombinant nucleic acid encoding the multiepitopic polypeptide.
  • the multiepitopic polypeptide comprises a first amino acid sequence comprising a first epitope sequence from a cancer protein.
  • the multiepitopic polypeptide comprises a second amino acid sequence comprising a second epitope sequence from the cancer protein.
  • the first epitope sequence and the second epitope sequence are the same.
  • the first epitope sequence and the second epitope sequence are different.
  • the first epitope sequence or the second epitope sequence are linked by a linker.
  • the multiepitopic polypeptide does not comprise the full-length cancer protein.
  • the subject has been previously treated with a TCR. In some embodiments, the subject has been previously treated with a recombinant acid encoding the TCR.
  • the TCR recognizes and binds to a peptide:MHC complex.
  • the peptide:MHC complex comprises the first epitope sequence and a human MHC encoded by an HLA allele.
  • the peptide:MHC complex comprises the second epitope sequence and a human MHC encoded by an HLA allele.
  • Provided herein is a method of treating a subject with a disease or condition.
  • the disease or condition is a cancer.
  • the method comprises administering to the subject a therapy.
  • the therapy comprises a TCR.
  • the therapy comprises a recombinant nucleic acid encoding the TCR.
  • the therapy comprises a cell comprising the TCR. In some embodiments, the therapy comprises a cell comprising a recombinant nucleic acid encoding the TCR. In some embodiments, the TCR recognizes and binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises an epitope sequence form a cancer protein and a human MHC encoded by an HLA allele. In some embodiments, the subject has been previously treated with a multiepitopic polypeptide. In some embodiments, the subject has been previously treated with a recombinant nucleic acid encoding the multiepitopic polypeptide.
  • the subject has been previously treated with a cell comprising a multiepitopic polypeptide.
  • the WSGR Docket No.50401-795.601 subject has been previously treated with a cell comprising a recombinant nucleic acid encoding the multiepitopic polypeptide.
  • the multiepitopic polypeptide comprises a first amino acid sequence comprising a first epitope sequence from a cancer protein.
  • the multiepitopic polypeptide comprises a second amino acid sequence comprising a second epitope sequence from the cancer protein.
  • the first epitope sequence and the second epitope sequence are the same.
  • the first epitope sequence and the second epitope sequence are different. In some embodiments, the first epitope sequence or the second epitope sequence are linked by a linker. In some embodiments, the multiepitopic polypeptide does not comprise the full-length cancer protein. In some embodiments the first epitope sequence or the second epitope sequence is the epitope sequence recognized by the TCR. [0634] Provided herein is a method of treating a subject with a disease or condition. In some embodiments, the disease or condition is a cancer. In some embodiments, the method comprises administering to the subject a first therapy. In some embodiments the first therapy comprises a multiepitopic polypeptide.
  • the first therapy comprises a recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the first therapy comprises a cell comprising a multiepitopic polypeptide. In some embodiments, the first therapy comprises a cell comprising a recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide comprises a first amino acid sequence comprising a first epitope sequence from a cancer protein. In some embodiments, the multiepitopic polypeptide comprises a second amino acid sequence comprising a second epitope sequence from the cancer protein. In some embodiments, the first epitope sequence and the second epitope sequence are the same.
  • the first epitope sequence and the second epitope sequence are different. In some embodiments, the first epitope sequence or the second epitope sequence are linked by a linker. In some embodiments, the multiepitopic polypeptide does not comprise the full-length cancer protein. In some embodiments, the method comprises administering to the subject a second therapy. In some embodiments, the second therapy comprises a TCR. In some embodiments, the second therapy comprises a recombinant nucleic acid encoding the TCR. In some embodiments, the second therapy comprises a cell comprising a TCR. In some embodiments, the second therapy comprises a cell comprising a recombinant nucleic acid encoding the TCR.
  • the TCR recognizes and binds to a peptide:MHC complex.
  • the peptide:MHC complex comprises the first epitope sequence and a human MHC encoded by an HLA allele.
  • the peptide:MHC complex comprises the second epitope sequence and a human MHC encoded by an HLA allele.
  • the first therapy is administered prior to the second therapy. In some embodiments, the first therapy is administered concurrently with the second therapy. In some embodiments, the first therapy is administered subsequent to the second therapy.
  • presentation of the first and/or second epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject is higher than the presentation of the first and/or second epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length cancer protein or a recombinant nucleic acid encoding the full-length cancer protein.
  • the cancer protein is RAS.
  • the TCR recognizes an epitope derived from the cancer protein.
  • the method comprises administering two or more different TCRs.
  • the method comprises administering two or more recombinant nucleic acids encoding the two or more different TCRs.
  • the two or more TCRs comprise a first TCR and a second TCR.
  • the two or more different TCRs are expressed on the surface of two different immune cells.
  • the first TCR and the second TCR bind to different peptide:MHC complexes, each peptide:MHC complex comprising (i) an epitope sequence and (ii) a human MHC encoded by an HLA allele.
  • the two or more different TCRs are administered separately or co-administered in a same mixture.
  • recombinant nucleic acids encoding the two or more different TCRs are administered separately or co-administered in a same mixture.
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75-79
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 27, 58- 62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA- A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA- C*03:03, HLA-C*03:04, HLA-DRB1*07:01 and, HLA-A*03 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:
  • the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75-79 and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01 and the second TCR binds to a peptide:MHC WSGR Docket No.50401-795.601 complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting HLA- DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03.
  • the APCs of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide present more of an epitope sequence derived from the cancer protein as a peptide:MHC complex compared to the APCs of a subject administered a full-length cancer protein.
  • the T cells of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide exhibit increased expansion compared to T cells of a subject administered a full-length cancer protein or a recombinant nucleic acid encoding the full-length cancer protein.
  • the cell is an APC.
  • the APC has been incubated with the multiepitopic polypeptide.
  • the APC has been incubated with the recombinant nucleic acid encoding the multiepitopic polypeptide.
  • the multiepitopic polypeptide comprises at least 2, 3, 4, 5, or more different epitope sequences derived from a cancer protein. [0637]
  • binding of the TCR to the peptide:MHC complex results in production of a cytokine by the immune cell.
  • the cytokine is IFN- ⁇ .
  • the cytokine is IL-2.
  • the cytokine is TNF- ⁇ . In some embodiments, production of the cytokine is increased by about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% or more compared to an otherwise identical TCR recognizing an irrelevant peptide:MHC complex. In some embodiments, production of the cytokine is increased by about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% or more compared to an otherwise identical APC presenting a wild type RAS antigen.
  • T Cell Activation [0638]
  • the methods and compositions disclosed herein can comprise RAS-specific T cells that can be delivered to a subject having cancer.
  • RAS -specific T cells can be generated by NEO-STIM, a process of T cell activation and/or expansion.
  • Generating antigen specific (e.g., RAS -specific) T cells by controlled ex vivo induction or expansion of T cells can provide highly specific and beneficial T cell and T- cell receptors (TCRs).
  • TCRs T cell manufacturing methods, TCRs, therapeutic T cell compositions which can be used for treating cancer.
  • the TCRs can be used for validating a whether its cognate epitope sequence is presented by a cell of interest and can be used for validating whether a candidate antigen is suitable for use as a part of a vaccine design.
  • the first step is to expand and induce antigen specific T cells with a favorable phenotype and function.
  • the present disclosure provides compositions and methods for WSGR Docket No.50401-795.601 manufacturing of T cells which can be used for antigen specific T cell therapy (e.g., personal or personalized T cell therapies for treating cancer).
  • the T cell compositions provided herein can be personal antigen specific T cell therapies.
  • the process includes on one hand, identification of the cancer-specific antigens, leading to the production of antigenic peptides or mRNAs encoding such antigenic peptides; and on the other hand, preparing activated, antigen specific cells for immunotherapy and identification of functional TCRs that can be used in TCR recognition assays as described herein.
  • the NEO-STIM process can comprise methods of preparing activated, antigen-specific T cells.
  • Provided herein are methods for stimulating T cells.
  • the methods provided herein can be used to stimulate antigen specific T cells.
  • the methods provided herein can be used to induce or activate T cells.
  • the methods provided herein can be used to expand activated T cells.
  • the methods provided herein can be used to induce na ⁇ ve T cells.
  • the methods provided herein can be used to expand antigen specific CD8+ T cells.
  • the methods provided herein can be used to expand antigen specific CD4+ T cells.
  • the methods provided herein can be used to expand antigen specific CD8+ T cells having memory phenotype.
  • the therapeutic compositions can comprise antigen specific CD8+ T cells.
  • the therapeutic compositions can comprise antigen specific memory T cells.
  • T cells can be activated ex vivo with a composition comprising antigenic peptides or polynucleotides encoding the antigenic peptides.
  • T cells can be activated ex vivo with a composition comprising antigen loaded antigen- presenting cells.
  • the APCs and/or T cells are derived from a biological sample which is obtained from a subject.
  • the APCs and/or T cells are derived from a biological sample which is peripheral blood mononuclear cells (PBMC).
  • PBMC peripheral blood mononuclear cells
  • the subject is administered FLT3L prior to obtaining the biological sample for preparing the APCs and/or T cells.
  • the APCs and/or T cells are derived from a biological sample, for example, from healthy human donors.
  • antigen-presenting cells are first loaded with antigenic peptides ex vivo and used to prepare antigen activated T cells.
  • the compositions provided herein comprise T cells that are stimulated by APCs, such as APCs pre-loaded with antigen peptides.
  • compositions can comprise a population of immune cells comprising T cells from a sample (e.g., a WSGR Docket No.50401-795.601 biological sample), wherein the T cells comprise APC-stimulated T cells.
  • a sample e.g., a WSGR Docket No.50401-795.601 biological sample
  • mRNA encoding one or more antigenic peptides are introduced into APCs for expression of the antigenic peptides.
  • Such APCs are used for stimulating or activating T cells.
  • the biological sample comprises a percentage of the at least one antigen specific T cell in the composition is at least about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%.
  • the biological sample comprises less than 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%.1%, 2%, 3%, 4%, 5%, or less than 10% antigen activated T cells of the total cell count in the biological sample that is derived from peripheral blood or leukapheresis. In some embodiments, the biological sample comprises less than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30% antigen activated T cells of the total cell count in the biological sample that is derived from peripheral blood.
  • the biological sample comprises antigen naive T cells.
  • the biological sample comprises greater than about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% antigen naive cells of the total cell count in the biological sample that is derived from peripheral blood or leukapheresis.
  • a percentage of at least one antigen specific CD8+ T cell in the composition is less than about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5% in the biological sample derived from peripheral blood or leukapheresis.
  • a percentage of at least one antigen specific CD4+ T cell in the composition is at least about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, of in the biological sample derived from peripheral blood or leukapheresis.
  • a percentage of the at least one antigen specific T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of the total immune cells.
  • a percentage of at least one antigen specific CD8+ T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of the total immune cells.
  • a percentage of at least one antigen specific CD4+ T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of the total immune cells. In some embodiments, a percentage of antigen specific T cells in the biological sample is at most about 0.5%. In some embodiments, a percentage of antigen specific WSGR Docket No.50401-795.601 CD8+ T cells in the biological sample is at most about 0.5%. In some embodiments, a percentage of antigen specific CD4+ T cells in the biological sample is at most about 0.5% in the biological sample.
  • the NEO-STIM process can comprise methods of preparing antigen loaded APCs.
  • a composition comprises a population of immune cells that has been incubated with one or more cytokines, growth factors or ligands, such as a ligand that binds to a cell surface receptor of an APC or a T cell.
  • cytokines, growth factors and ligands include, for example, GM-CSF, IL-4, IL-7, FLT3L, TNF- ⁇ , IL-1 ⁇ , IL-15, PGE1, IL-6, IFN- ⁇ , INF- ⁇ , R848, LPS, ss-rna40, and poly(I:C).
  • a composition comprises a population of immune cells that has been incubated with one or more APCs or APC preparations.
  • a composition can comprise a population of immune cells that has been incubated with one or more cytokine, growth factor and/or ligand stimulated APCs or cytokine, growth factor and/or ligand stimulated APC preparations.
  • a composition can comprise a population of immune cells that has been incubated with one or more cytokine stimulated APCs or cytokine stimulated APC preparations.
  • a composition can comprise a population of immune cells that have been incubated with one or more growth factor stimulated APCs or growth factor stimulated APC preparations.
  • a composition can comprise a population of immune cells that has been incubated with one or more ligand stimulated APCs or ligand stimulated APC preparations.
  • the APC is an autologous APC, an allogenic APC, or an artificial APC.
  • the APC is an artificial APC.
  • Immune cells can be characterized by cell surface molecules.
  • the immune cells are preferably selected based on the cell surface markers, for example, from the biological sample, by using antibodies that can bind to the cell surface receptors. In some embodiments some cells are negatively selected to enrich one or more cell types that do not express the cell surface molecule that they are negatively selected for.
  • antigen-presenting cells are prepared from the biological sample by selecting from APCs or precursor cells that can be cultured in presence of antigenic peptides to generate antigen-loaded APCs, which are used for activating T cells.
  • CD1 cluster of differentiation 1 is a family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells.
  • CD11b or Integrin alpha M is one protein subunit that forms heterodimeric integrin alpha-M beta-2 ( ⁇ M ⁇ 2) molecule, also known as macrophage-1 antigen (Mac-1) or complement receptor 3(CR3). ITGAM is also known as CR3A, and cluster of WSGR Docket No.50401-795.601 differentiation molecule 11b (CD11b).
  • the second chain of ⁇ M ⁇ 2 is the common integrin ⁇ 2 subunit known as CD18, and integrin ⁇ M ⁇ 2 thus belongs to the ⁇ 2 subfamily (or leukocyte) integrins.
  • ⁇ M ⁇ 2 is expressed on the surface of many leukocytes involved in the innate immune system, including monocytes, granulocytes, macrophages, and natural killer cells. It mediates inflammation by regulating leukocyte adhesion and migration and has been implicated in several immune processes such as phagocytosis, cell-mediated cytotoxicity, chemotaxis and cellular activation. It is involved in the complement system due to its capacity to bind inactivated complement component 3b (iC3b).
  • iC3b inactivated complement component 3b
  • CD11c also known as Integrin, alpha X (complement component 3 receptor 4 subunit) (ITGAX), is a gene that encodes for CD11c.
  • CD11c is an integrin alpha X chain protein. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This protein combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as inactivated-C3b (iC3b) receptor 4 (CR4).
  • CD11c is a type I transmembrane protein found at high levels on most human dendritic cells, but also on monocytes, macrophages, neutrophils, and some B cells that induces cellular activation and helps trigger neutrophil respiratory burst; expressed in hairy cell leukemias, acute nonlymphocytic leukemias, and some B-cell chronic lymphocytic leukemias.
  • CD14 is a surface antigen that is preferentially expressed on monocytes/macrophages.
  • CD14 exists in two forms, one anchored to the membrane by a glycosylphosphatidylinositol tail (mCD14), the other a soluble form (sCD14). Soluble CD14 either appears after shedding of mCD14 (48 kDa) or is directly secreted from intracellular vesicles (56 kDa). CD14 acts as a co-receptor (along with the Toll-like receptor TLR 4 and MD-2) for the detection of bacterial lipopolysaccharide (LPS).
  • mCD14 glycosylphosphatidylinositol tail
  • sCD14 soluble form
  • Soluble CD14 either appears after shedding of mCD14 (48 kDa) or is directly secreted from intracellular vesicles (56 kDa).
  • CD14 acts as a co-receptor (along with the Toll-like receptor TLR 4 and MD-2) for the detection of bacterial lipopolysacc
  • CD14 can bind LPS only in the presence of lipopolysaccharide-binding protein (LBP). Although LPS is considered its main ligand, CD14 also recognizes other pathogen-associated molecular patterns such as lipoteichoic acid.
  • LBP lipopolysaccharide-binding protein
  • CD14 also recognizes other pathogen-associated molecular patterns such as lipoteichoic acid.
  • CD25 is expressed by conventional T cells after stimulation, and it has been shown that in human peripheral blood, only the CD4+CD25hi T cells are 'suppressors'.
  • the APC comprises a dendritic cell (DC).
  • the APC is derived from a CD14+ monocyte.
  • the APCs can be obtained from skin, spleen, bone marrow, thymus, lymph nodes, peripheral blood, or cord blood.
  • WSGR Docket No.50401-795.601 the CD14+ monocyte is from a biological sample from a subject comprising PBMCs.
  • a CD14+ monocyte can be isolated from, enriched from, or purified from a biological sample from a subject comprising PBMCs.
  • the CD14+ monocyte is stimulated with one or more cytokines or growth factors.
  • the one or more cytokines or growth factors comprise GM-CSF, IL-4, FLT3L, TNF- ⁇ , IL-1 ⁇ , PGE1, IL-6, IL-7, IL-15, IFN- ⁇ , IFN- ⁇ , R848, LPS, ss-rna40, poly I:C, or a combination thereof.
  • the CD14+ monocyte is from a second biological sample comprising PBMCs.
  • an isolated population of APCs can be enriched or substantially enriched. In some embodiments, the isolated population of APCs is at least 30%, at least 50%, at least 75%, or at least 90% homogeneous.
  • the isolated population of APCs is at least 60%, at least 75%, or at least 90% homogeneous.
  • APCs such as APCs can include, for example, APCs derived in culture from monocytic dendritic precursors as well as endogenously-derived APCs present in tissues such as, for example, peripheral blood, cord blood, skin, spleen, bone marrow, thymus, and lymph nodes.
  • APCs and cell populations substantially enriched for APCs can be isolated by methods also provided by the present disclosure.
  • the methods generally include obtaining a population of cells that includes APC precursors, differentiation of the APC precursors into immature or mature APCs, and can also include the isolation of APCs from the population of differentiated immature or mature APCs.
  • APC precursor cells can be obtained by methods known in the art.
  • APC precursors can be isolated, for example, by density gradient separation, fluorescence activated cell sorting (FACS), immunological cell separation techniques such as panning, complement lysis, rosetting, magnetic cell separation techniques, nylon wool separation, and combinations of such methods.
  • Methods for immuno-selecting APCs include, for example, using antibodies to cell surface markers associated with APC precursors, such as anti-CD34 and/or anti-CD14 antibodies coupled to a substrate.
  • Enriched populations of APC precursors can also be obtained. Methods for obtaining such enriched precursor populations are known in the art. For example, enriched populations of APC precursors can be isolated from a tissue source by selective removal of cells that adhere to a substrate. Using a tissue source such as, e.g., bone marrow or peripheral blood, adherent monocytes can be removed from cell preparations using a commercially-treated plastic substrate (e.g., beads or magnetic beads) to obtain a population enriched for nonadherent APC precursors. [0668] Monocyte APC precursors can also be obtained from a tissue source by using an APC precursor-adhering substrate.
  • tissue source such as, e.g., bone marrow or peripheral blood
  • adherent monocytes can be removed from cell preparations using a commercially-treated plastic substrate (e.g., beads or magnetic beads) to obtain a population enriched for nonadherent APC precursors.
  • Monocyte APC precursors can also be obtained from
  • peripheral blood leukocytes isolated by, e.g., leukapheresis are contacted with a monocytic APC precursor-adhering substrate having a high surface area to volume ratio and the adherent monocytic APC precursors are separated.
  • the substrate coupled can be a particulate or fibrous substrate having a high surface-to- volume ratio, such as, for example, microbeads, microcarrier beads, pellets, granules, powder, capillary tubes, microvillous membrane, and the like.
  • the particulate or fibrous substrate can be glass, polystyrene, plastic, glass-coated polystyrene microbeads, and the like.
  • the APC precursors can also be cultured in vitro for differentiation and/or expansion. Methods for differentiation/expansion of APC precursors are known in the art. Generally, expansion can be achieved by culturing the precursors in the presence of at least one cytokine that induces APC (e.g., dendritic cell) differentiation/proliferation. Typically, these cytokines are granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor (GM-CSF).
  • G-CSF granulocyte colony stimulating factor
  • GM-CSF granulocyte/macrophage colony stimulating factor
  • cultures of APC precursors during expansion, differentiation, and maturation to the APC phenotype can include plasma to promote the development of APCs.
  • a typical plasma concentration is about 5%.
  • plasma can be included in the culture media during the adherence step to promote the CD14+ phenotype early in culture.
  • a typical plasma concentration during adherence is about 1% or more.
  • the monocytic APC precursors can be cultured for any suitable time.
  • suitable culture times for the differentiation of precursors to immature APCs can be about 1 to about 10 days, e.g., about 4 to about 7 days.
  • the differentiation of immature APCs from the precursors can be monitored by methods known to those skilled in the art, such as by the presence or absence of cell surface markers (e.g., CD11c+, CD83low, CD86 ⁇ /low, HLA-DR+).
  • Immature APCs can also be cultured in appropriate tissue culture medium to maintain the immature APCs in a state for further differentiation or antigen uptake, processing and presentation.
  • immature APCs can be maintained in the presence of GM-CSF and IL-4.
  • Non-adhering CD14 ⁇ cells are then washed from the substrate, and the adherent cells are then eluted to obtain an isolated cell population substantially enriched in APC precursors.
  • the CD14 specific probe can be, for example, an anti-CD14 antibody.
  • the substrate can be, for example, commercially available tissue culture plates or beads (e.g., glass or magnetic beads). Methods for affinity isolation of cell populations using substrate-coupled antibodies specific for surface markers are generally known.
  • immature APCs can optionally be exposed to a predetermined antigen. Suitable predetermined antigens can include any antigen for which T-cell modulation is desired.
  • Antigens can include, for example, bacterial cells, viruses, partially purified or purified bacterial, viral, fungal, protozoan, or helminth antigens, recombinant cells expressing an antigen on its surface, and any other antigen. Any of the antigens can also be presented as a peptide or recombinantly produced protein or portion thereof. Following contact with antigen, the cells can be cultured for any suitable time to allow antigen uptake and processing, to expand the population of antigen-specific APCs, and the like. [0676] For example, in some embodiments, the immature APCs can be cultured following antigen uptake to promote maturation of the immature APCs into mature APCs that present antigen in the context of MHC molecules.
  • APC maturation can be performed, for example, by culture in the presence of known maturation factors, such as cytokines (e.g., TNF- ⁇ , IL-1 ⁇ , or CD40 ligand), bacterial products (e.g., LPS or BCG), and the like.
  • cytokines e.g., TNF- ⁇ , IL-1 ⁇ , or CD40 ligand
  • bacterial products e.g., LPS or BCG
  • the maturation of immature APCs to mature APCs can be monitored by methods known in the art, such as, for example by measuring the presence or absence of cell surface markers (e.g., upregulation of CD83, CD86, and MHC molecules) or testing for the expression of mature APC specific mRNA or proteins using, for example, an oligonucleotide array.
  • the immature APCs can be cultured in an appropriate tissue culture medium to expand the cell population and/or maintain the immature APCs in state for further differentiation or WSGR Docket No.50401-795.601 antigen uptake.
  • immature APCs can be maintained and/or expanded in the presence of GM-CSF and IL-4.
  • the immature APCs can be cultured in the presence of anti-inflammatory molecules such as, for example, anti-inflammatory cytokines (e.g., IL-10 and TGF- ⁇ ) to inhibit immature APC maturation.
  • the isolated population of APCs is enriched for mature APCs.
  • the isolated population of mature APCs can be obtained by culturing a differentiated population of immature APCs in the presence of maturation factors as described above (e.g., bacterial products, and/or proinflammatory cytokines), thereby inducing maturation. Immature APCs can be isolated by removing CD14+ cells. [0679] According to yet another aspect of the present disclosure, APCs can be preserved, e.g., by cryopreservation either before exposure or following exposure to a suitable antigen.
  • maturation factors as described above (e.g., bacterial products, and/or proinflammatory cytokines)
  • Cryopreservation agents which can be used include dimethyl sulfoxide (DMSO), glycerol, polyvinylpyrrolidone, polyethylene glycol, albumin, dextran, sucrose, ethylene glycol, i-erythritol, D-ribitol, D-mannitol, D- sorbitol, i-inositol, D-lactose, choline chloride, amino acids, methanol, acetamide, glycerol monoacetate, and inorganic salts.
  • a controlled slow cooling rate can be critical. Different cryoprotective agents and different cell types may have different optimal cooling rates.
  • the heat of fusion phase where water turns to ice typically can be minimal.
  • the cooling procedure can be carried out by use of, e.g., a programmable freezing device or a methanol bath procedure.
  • Programmable freezing apparatuses allow determination of optimal cooling rates and facilitate standard reproducible cooling.
  • Programmable controlled-rate freezers such as Cryomed or Planar permit tuning of the freezing regimen to the desired cooling rate curve.
  • APCs can be rapidly transferred to a long-term cryogenic storage vessel.
  • samples can be cryogenically stored in liquid nitrogen ( ⁇ 196 °C) or its vapor ( ⁇ 165 °C).
  • Frozen cells are preferably thawed quickly (e.g., in a water bath maintained at 37-41 °C) and chilled immediately upon thawing. It can be desirable to treat the cells in order to prevent cellular clumping upon thawing. To prevent clumping, various procedures can be used, including the addition before and/or after freezing of DNAse, low molecular weight dextran and citrate, hydroxyethyl starch, and the like.
  • a composition for T cell activation comprises a population of immune cells that has been depleted of one or more types of immune cells.
  • a composition can comprise a population of immune cells that has been depleted of one or more types of immune cells that express one or more proteins, such as one or more cell surface receptors.
  • a composition comprises a population of immune cells from a biological sample comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, wherein an amount of CD14 and/or CD25 expressing immune cells in the population is proportionally different from an amount of immune cells expressing CD14 and/or CD25 in the biological sample.
  • a composition can comprise a population of immune cells from a biological sample comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, wherein an amount of CD14 expressing immune cells in the population is proportionally different from an amount of immune cells expressing CD14 in the biological sample.
  • a composition can comprise a population of immune cells from a biological sample comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, wherein an amount of CD25 expressing immune cells in the population is proportionally different from an amount of immune cells expressing CD25 in the biological sample.
  • a composition can comprise a population of immune cells from a biological sample comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, wherein an amount of CD14 and CD25 expressing immune cells in the population is proportionally different from an amount of immune cells expressing CD14 and CD25 in the biological sample.
  • TCR T-cell receptor
  • a composition can comprise a population of immune cells from a biological sample, wherein an amount of immune cells expressing CD14 and CD25 in the population is proportionally less than an amount of immune cells expressing CD14 and CD25 in the biological sample.
  • a method of preparing antigen-specific T cells ex vivo the method comprises (a) depleting CD14+ cells and/or CD25+ cells from a population of immune cells comprising antigen-presenting cells (APCs) and T cells, thereby forming a CD14 and/or CD25 depleted population of immune cells comprising a first population of APCs and T cells, wherein the population of immune cells is from a biological sample from a human subject; (b) incubating the first population of APCs and T cells from (a) for a first time period in the presence of: (i) FMS-like tyrosine kinase 3 receptor ligand (FLT3L), and (ii) (A) a polypeptide comprising
  • the expanded population of cells comprises from at least 5x105 to at least 5x1011 total cells. In some embodiments, the expanded population of cells comprises at least 1x106 total cells. In some embodiments, the expanded population of cells comprises at least 5x106 total cells. In some embodiments, the expanded population of cells comprises at least 1x107 total cells. In some embodiments, the expanded population of cells comprises at least 5x107 total cells. In some embodiments, the expanded population of cells comprises at least 1x108 total cells. In some embodiments, the expanded population of cells comprises at least 5x108 total cells. In some embodiments, the expanded population of cells comprises at least 1x109 total cells. In some embodiments, the expanded population of cells comprises at least 5x109 total cells.
  • the expanded population of cells comprises at least 1x1010 total cells. In some embodiments, the expanded population of cells comprises at least 5x1010 total cells. In some embodiments, the expanded population of cells comprises at least 1x1011 total cells. In some embodiments, the expanded population of cells comprises at least 5x1011 total cells. In some embodiments, the expanded population of cells comprises from 1x108 to 1x1011 total cells. In some embodiments, the expanded population of cells comprises from 0,75x108 to 1.25x1010 total cells. In some embodiments the expanded population of cells comprises from 5x108 to 1x109 total cells. In some embodiments, the expanded population of cells comprises 5x108 to 1x109 total cells. In some embodiments, the expanded population of cells comprises 5x108 to 2x109 total cells.
  • the subject is pretreated with FLT3L at least about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 1 week before isolation of PBMC or leukapheresis. In some embodiments, the subject is pretreated with FLT3L at least about 1 week, 2 weeks, 3 weeks, 4 weeks, or 5 weeks before isolation of PBMC or leukapheresis. [0686] In some embodiments, the cell population is enriched for CD11c+ cells. In some embodiments, the antigen loaded APC comprises dendritic cells (DCs).
  • DCs dendritic cells
  • the antigen loaded APC comprises plasmacytoid dendritic cells (pDCs). In some embodiments, the antigen loaded APC comprises CD1c+ DCs. In some embodiments, the antigen loaded APC comprises CD141+ DCs. In some embodiments, the cell population comprises macrophages. In some embodiments, the method further comprises reducing or depleting CD19+ cells from the cell population for activating or enriching antigen activated T cells. In some embodiments, the method further comprises reducing or depleting both CD11b+ and CD19+ cells from the cell population for activating or enriching antigen activated T cells.
  • the method further comprises reducing or depleting CD14+ cells from the cell population for preparing and enriching antigen activated T cells. In some embodiments, the method further comprises reducing or depleting CD25+ cells from the cell population for preparing and enriching antigen activated T cells. In some embodiments, the method further comprises reducing or depleting one or more of CD19+, CD14+, CD25+ or CD11b+ cells from the cell population for activating or enriching antigen activated T cells. In some embodiments, depleting comprises depleting CD14+ cells directly from a washed peripheral blood mononuclear cell (PBMC) sample from a human subject.
  • PBMC peripheral blood mononuclear cell
  • depleting comprises depleting CD25+ cells directly from a washed peripheral blood mononuclear cell (PBMC) sample from a human subject. In some embodiments, depleting comprises depleting CD14+ cells and CD25+ cells directly from a washed peripheral blood mononuclear cell (PBMC) sample from a human subject. In some embodiments, depleting comprises depleting CD14+ cells directly from a cryopreserved peripheral blood mononuclear cell (PBMC) sample from a human subject. In some embodiments, depleting comprises depleting CD25+ cells directly from a cryopreserved peripheral blood mononuclear cell (PBMC) sample from a human subject.
  • PBMC washed peripheral blood mononuclear cell
  • depleting comprises depleting CD14+ cells and CD25+ cells directly from a cryopreserved peripheral blood mononuclear cell (PBMC) sample from a human subject.
  • PBMC peripheral blood mononuclear cell
  • the depleted population of cells is incubated for a first time period in the presence of FLT3L and a polypeptide comprising at least two different epitope sequences.
  • the depleted population of cells is incubated for a first time period in the presence of FLT3L and a polynucleic acid encoding a polypeptide comprising at least two different epitope sequences.
  • each of the at least two different epitope sequences is from the same protein encoded by the genome of a cancer cell.
  • each of the at least two different epitope sequences is from a different protein encoded by the genome of a cancer cell.
  • the same protein encoded by the genome of a cancer cell is RAS.
  • a first epitope sequence of the at least two different epitope sequences are connected to a second epitope sequence of the at least 2 different epitope sequences via a linker sequence.
  • the at least two different epitope sequences are expressed as a single polypeptide chain.
  • the polypeptide comprises at least 2 to at least 15 or more different epitope sequences from two or more different proteins encoded by the genome of a cancer cell.
  • the polypeptide comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10 or more different epitope sequences from two or more different proteins encoded by the genome of a cancer cell.
  • the method comprises introducing the polynucleotide encoding the polypeptide or the mRNA encoding the polypeptide into the APCs of the first population of APCs and T cells.
  • introducing comprises electroporating.
  • WSGR Docket No.50401-795.601 introducing comprises nucleofecting.
  • introducing is carried out without separating the T cells from the APCs of the first population of APCs and T cells.
  • the method is performed in less than 35 days. In some embodiments, the method is performed in less than 30 days. In some embodiments, the method is performed in less than 28 days. In some embodiments, the method is performed in less than 25 days. In some embodiments, the method is performed in less than 20 days, in some embodiments. the method is performed in less than 15 days. In some embodiments, the method is performed in less than 10 days. In some embodiments, the method is performed in less than 5 days. In some embodiments, CD8+ antigen-specific T cells are expanded. In some embodiments CD4+ antigen-specific T cells are expanded.
  • the fraction of CD8+ antigen-specific T cells of the total number of T cells in the expanded population of cells is at least two-fold higher than the fraction of CD8+ antigen-specific T cells of the total number of CD8+ T cells in the CD14 and/or CD25 depleted population of immune cell.
  • the fraction of CD8+ antigen-specific T cells of the total number of T cells in the expanded population of cells is at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold higher than the fraction of CD8+ antigen-specific T cells of the total number of CD8+ T cells in the CD14 and/or CD25 depleted population of immune cell.
  • the fraction of CD4+ antigen-specific T cells of the total number of T cells in the expanded population of cells is at least two-fold higher than the fraction of CD4+ antigen-specific T cells of the total number of CD4+ T cells in the CD14 and/or CD25 depleted population of immune cell.
  • the fraction of CD4+ antigen-specific T cells of the total number of T cells in the expanded population of cells is at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold higher than the fraction of CD4+ antigen-specific T cells of the total number of CD4+ T cells in the CD14 and/or CD25 depleted population of immune cell.
  • at least 0.1% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from na ⁇ ve CD8+ T cells.
  • At least 0.5% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from na ⁇ ve CD8+ T cells. In some embodiments, at least 1% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from na ⁇ ve CD8+ T cells. In some embodiments, at least 5% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from na ⁇ ve CD8+ T cells. In some embodiments, at least 10% of the CD8+ T cells in the expanded population of cells are CD8+ antigen- specific T cells derived from na ⁇ ve CD8+ T cells.
  • At least 20% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from na ⁇ ve CD8+ T cells. In some embodiments, at least 30% of the CD8+ T cells in the expanded population of cells WSGR Docket No.50401-795.601 are CD8+ antigen-specific T cells derived from na ⁇ ve CD8+ T cells. In some embodiments, at least 40% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from na ⁇ ve CD8+ T cells.
  • At least 50% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from na ⁇ ve CD8+ T cells. In some embodiments, at least 60% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from na ⁇ ve CD8+ T cells. In some embodiments, at least 70% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from na ⁇ ve CD8+ T cells. In some embodiments, at least 80% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from na ⁇ ve CD8+ T cells.
  • At least 90% of the CD8+ T cells in the expanded population of cells are CD8+ antigen- specific T cells derived from na ⁇ ve CD8+ T cells.
  • at least 0.1% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from na ⁇ ve CD4+ T cells.
  • at least 0.5% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from na ⁇ ve CD4+ T cells.
  • at least 1% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from na ⁇ ve CD4+ T cells.
  • At least 5% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from na ⁇ ve CD4+ T cells. In some embodiments, at least 10% of the CD4+ T cells in the expanded population of cells are CD4+ antigen- specific T cells derived from na ⁇ ve CD4+ T cells. In some embodiments, at least 20% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from na ⁇ ve CD4+ T cells. In some embodiments, at least 30% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from na ⁇ ve CD4+ T cells.
  • At least 40% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from na ⁇ ve CD4+ T cells. In some embodiments, at least 50% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from na ⁇ ve CD4+ T cells. In some embodiments, at least 60% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from na ⁇ ve CD4+ T cells. In some embodiments, at least 70% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from na ⁇ ve CD4+ T cells.
  • the expanding comprises contacting the population of cells comprising stimulated T cells with a second population of mature APCs. In some embodiments, the second population of mature APCs have been incubated with FLT3L.
  • the second WSGR Docket No.50401-795.601 population of mature APCs have been incubated with FLT3L for at least 1 day prior to contacting the population of cells comprising stimulated T cells with the second population of mature APCs.
  • the second population of mature APCs have been incubated with FLT3L for 2 days.
  • the second population of mature APCs have been incubated with FLT3L for 3 days.
  • the second population of mature APCs have been incubated with FLT3L for 4 days.
  • the second population of mature APCs have been incubated with FLT3L for 5 days.
  • the second population of mature APCs present the peptide consisting of the epitope sequence from the protein encoded by the genome of the cancer cells.
  • the second population of mature APCs have been incubated with FLT3L and present the peptide consisting of the epitope sequence from the protein encoded by the genome of the cancer cell.
  • expanding comprises expanding the population of cells comprising stimulated T cells for a second time period, thereby forming an expanded population of T cells.
  • depleting CD14+ cells from the population of immune cells comprising a first population of APCs and T cells comprises contacting the population of immune cells comprising a first population of APCs and T cells with a CD14 binding agent.
  • depleting CD25+ cells from the population of immune cells comprising a first population of APCs and T cells comprises contacting the population of immune cells comprising a first population of APCs and T cells with a CD25 binding agent.
  • depleting CD14+ cells and/or CD25+ cells from the population of immune cells comprising a first population of APCs and T cells comprises contacting the population of immune cells comprising a first population of APCs and T cells with a CD14 binding agent and/or a CD25 binding agent.
  • the stimulant for activating the cells comprises FL3TL.
  • the agent promoting cell growth and maintenance ex vivo comprises a growth factor, a cytokine, an amino acid, a supplement or a combination thereof.
  • the antigen loaded APCs can stimulate T cells for 2, 3, 4, 5, 6, or 7 days.
  • the antigenic peptides used to prepare antigen loaded APCs are long peptides comprising at least 20 amino acids, or at least 30 amino acids or at least 40 amino acids or at least 50 amino acids, or any number of amino acids in between.
  • the antigenic peptides used to prepare antigen loaded APCs comprise the amino acids flanking on either side of the epitope that facilitate endogenous processing of the antigenic peptide for increased rate of presentation to a T cell.
  • a longer immunogenic peptide can be designed in several ways. In some embodiments, when HLA-binding peptides are predicted or known, a longer immunogenic peptide could consist of (1) individual binding peptides with extensions of 2-5 amino acids toward the N- and C-terminus of each WSGR Docket No.50401-795.601 corresponding gene product; or (2) a concatenation of some or all of the binding peptides with extended sequences for each.
  • a longer antigen peptide when sequencing reveals a long (>10 residues) epitope sequence, e.g., an epitope derived from a protein encoded by a gene in a cancer cell (e.g., due to a frameshift, read-through or intron inclusion that leads to a novel peptide sequence), a longer antigen peptide could consist of the entire stretch of novel antigen-specific amino acids as either a single longer peptide or several overlapping longer peptides. In some embodiments, use of a longer peptide is presumed to allow for endogenous processing by patient cells and can lead to more effective antigen presentation and induction of T cell responses.
  • each of the plurality of antigenic peptide comprises the same antigenic epitope. In some embodiments the plurality of antigenic peptide comprises more than one antigenic epitope.
  • the one or more polynucleotides encoding the plurality of antigen peptides is DNA.
  • the one or more polynucleotides encoding the plurality of antigen peptides is inserted in one or more mammalian expression vectors.
  • the one or more polynucleotides encoding the plurality of antigen peptides is messenger RNA.
  • the present disclosure provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising a modified nucleoside.
  • the present disclosure provides gene therapy vectors comprising the RNA, oligoribonucleotide, and polyribonucleotide.
  • the present disclosure provides gene therapy methods and gene transcription silencing methods comprising same.
  • the polynucleotide encodes a single antigenic peptide.
  • the one polynucleotide encodes more than one antigenic peptide.
  • the polynucleotide is messenger RNA.
  • each messenger RNA comprises coding sequence for two or more antigenic peptides in tandem.
  • each messenger RNA comprises a coding sequence for two, three, four, five, six, seven, eight, nine or ten or more antigenic peptides in tandem.
  • an mRNA comprises a 5'-UTR, a protein coding region, and a 3'-UTR. mRNA only possesses limited half-life in cells and in vitro.
  • the mRNA is self-amplifying mRNA.
  • mRNA can be generated by in vitro transcription from a DNA template.
  • the in vitro transcription methodology is known to the skilled person.
  • the stability and translation efficiency of RNA can be modified.
  • RNA can be stabilized, and its translation increased by one or more modifications having a stabilizing effect and/or increasing translation efficiency of RNA. Such modifications are described, for example, in PCT/EP2006/009448 incorporated herein by reference.
  • an mRNA can include multiple antigenic epitopes.
  • a mRNA of a large portion of, or even the entire coding region of a gene comprising sequences encoding antigenic peptides are delivered into an immune cell for endogenous processing and presentation of antigens.
  • the coding sequence for each antigenic peptide is 24-120 nucleotides long.
  • the mRNA is 50-10,000 nucleotides long. In some embodiments, the mRNA is 100- 10,000 nucleotides long. In some embodiments, the mRNA is 200-10,000 nucleotides long. In some embodiments, the mRNA is 50-5,000 nucleotides long. In some embodiments, the mRNA is 100-5,000 nucleotides long. In some embodiments, the mRNA is 100-1,000 nucleotides long. In some embodiments, the mRNA is 300-800 nucleotides long.
  • the mRNA is 400-700 nucleotides long. In some embodiments, the mRNA is 450-600 nucleotides long. In some embodiments, the mRNA is at least 200 nucleotides long. In some embodiments the mRNA is greater than 250 nucleotides, greater than 300 nucleotides, greater than 350 nucleotides, greater than 400 nucleotides, greater than 450 nucleotides, greater than 500 nucleotides, greater than 550 nucleotides, greater than 600 nucleotides, greater than 650 nucleotides, greater than 700 nucleotides, greater than 750 nucleotides, greater than 800 nucleotides, greater than 850 nucleotides long, greater than 900 nucleotides long greater than 950 nucleotides long, greater than 1000 nucleotides long, greater than 2000 nucleotides long, greater than 3000 nucleotides long, greater than 4000 nucleotides long
  • mRNA encoding one or more antigenic peptide is modified, wherein the modification relates to the 5’-UTR.
  • the modification relates to providing an RNA with a 5'-cap or 5’- cap analog in the 5’-UTR.
  • the term “5'-cap” refers to a cap structure found on the 5'-end of an mRNA molecule and generally consists of a guanosine nucleotide connected to the mRNA via an unusual 5' to 3' triphosphate linkage. In some embodiments, this guanosine is methylated at the 7-position.
  • RNA 5'-cap refers to a naturally occurring RNA 5'- cap, to the 7-methylguanosine cap (m G).
  • the term “5'-cap” WSGR Docket No.50401-795.601 includes a 5'-cap analog that resembles the RNA cap structure and is modified to possess the ability to stabilize RNA and/or enhance translation of RNA if attached thereto, in vivo and/or in a cell.
  • mRNA is capped co-transcriptionally.
  • the mRNA encoding one or more antigenic peptides comprise a 3’- UTR comprising a poly A tail.
  • the poly A tail is 100-200 bp long. In some embodiments, the poly A tail is longer than 20 nucleotides. In some embodiments, the poly A tail is longer than 50 nucleotides. In some embodiments, the poly A tail is longer than 60 nucleotides. In some embodiments, the poly A tail is longer than 70 nucleotides. In some embodiments, the poly A tail is longer than 80 nucleotides. In some embodiments, the poly A tail is longer than 90 nucleotides. In some embodiments, the poly A tail is longer than 100 nucleotides. In some embodiments, the poly A tail is longer than 110 nucleotides. In some embodiments, the poly A tail is longer than 120 nucleotides.
  • the poly A tail is longer than 130 nucleotides. In some embodiments, the poly A tail is longer than 140 nucleotides. In some embodiments, the poly A tail is longer than 150 nucleotides. In some embodiments, the poly A tail is longer than 160 nucleotides. In some embodiments, the poly A tail is longer than 170 nucleotides. In some embodiments, the poly A tail is longer than 180 nucleotides. In some embodiments, the poly A tail is longer than 190 nucleotides. In some embodiments, the poly A tail is longer than 200 nucleotides. In some embodiments, the poly A tail is longer than 210 nucleotides.
  • the poly A tail is longer than 220 nucleotides. In some embodiments, the poly A tail is longer than 230 nucleotides. In some embodiments, the poly A tail is longer than 100 nucleotides. In some embodiments, the poly A tail is longer than 240 nucleotides. In some embodiments, the poly A tail is longer than 100 nucleotides. In some embodiments, the poly A tail is about 250 nucleotides. [0712] In some embodiments, the poly A tail comprises 100-250 adenosine units. In some embodiments, the poly A tail comprises 120-130 adenine units. In some embodiments, the poly A tail comprises 120 adenine units.
  • the poly A tail comprises 121 adenine units. In some embodiments, the poly A tail comprises 122 adenine units. In some embodiments, the poly A tail comprises 123 adenine units. In some embodiments, the poly A tail comprises 124 adenine units. In some embodiments, the poly A tail comprises 125 adenine units. In some embodiments, the poly A tail as 129 bases. [0713] In some embodiments, the coding sequence for two consecutive antigenic peptides are separated by a spacer or linker. [0714] In some embodiments, the spacer or linker comprises up to 5000 nucleotide residues. An exemplary spacer sequence is GGCGGCAGCGGCGGCGGCGGCAGCGGCGGC.
  • Another exemplary spacer sequence is GGCGGCAGCCTGGGCGGCGGCGGCAGCGGC.
  • Another exemplary spacer sequence is GGCGTCGGCACC.
  • Another exemplary spacer sequence is WSGR Docket No.50401-795.601 CAGCTGGGCCTG.
  • Another exemplary spacer is a sequence that encodes a lysine, such as AAA or AAG.
  • Another exemplary spacer sequence is CAACTGGGATTG.
  • the mRNA comprises one or more additional structures to enhance antigen epitope processing and presentation by APCs.
  • the linker or spacer region can contain cleavage sites.
  • cleavage sites ensure cleavage of the protein product comprising strings of epitope sequences into separate epitope sequences for presentation.
  • the preferred cleavage sites are placed adjacent to certain epitopes in order to avoid inadvertent cleavage of the epitopes within the sequences.
  • the design of epitopes and cleavage regions on the mRNA encoding strings of epitopes are non-random.
  • an mRNA encoding an antigen peptide of the present disclosure is administered to a subject in need thereof.
  • the mRNA to be administered comprises at least one modified nucleoside-phosphate.
  • T cells are activated with antigenic peptides by artificial antigen- presenting cells.
  • artificial scaffolds are used to activate a T cell with antigenic peptides, the artificial scaffolds are loaded with antigenic peptides couples with an MHC antigen to which the antigenic peptide can bind with high affinity.
  • the additional structures comprise encoding specific domains from the proteins selected from a group MITD, SP1, and 10th Fibronectin Domain: 10FnIII.
  • the cells derived from peripheral blood or from leukapheresis are contacted with the plurality of antigen peptides, or one or more polynucleotides encoding the plurality of antigen peptides once or more than once to prepare the antigen loaded APCs.
  • the method comprises incubating the APC or one or more of the APC preparations with a first medium comprising at least one cytokine or growth factor for a first time period.
  • the method comprises incubating one or more of the APC preparations with at least one peptide for a second time period.
  • the enriched cells further comprise CD1c+ cells.
  • the cell population is enriched for CD11c+ and CD141+ cells.
  • the cell population comprising the antigen loaded APCs comprises greater than 1%, 2%, 3%, 4%, 5%, 6,7%, 8%, 9%, 10%, 15%, 20%, 25%, 30% 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% or more CD11c+ cells.
  • the cell population comprising the antigen loaded APCs comprises less than 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 20%, 10%, 8%, 7%, 6%, 5%, 4% or lower CD11b+ expressing cells.
  • the cell population comprising the antigen loaded APCs comprises greater than 1%, 2%, 3%, 4%, 5%, 6,7%, 8%, 9%, 10%, 15%, 20%, 25%, 30% 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% antigenic peptide expressing cells that are CD11c+.
  • the cell population comprising the antigen loaded APCs comprises greater than 1%, 2%, 3%, 4%, 5%, 6,7%, 8%, 9%, 10%, 15%, 20%, 25%, 30% 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% antigenic peptide expressing cells that are CD11c+ CD1c+, or CD141+ cells.
  • the antigen loaded APCs comprise mature APCs.
  • the method comprises obtaining a biological sample from a subject comprising at least one APC and at least one PBMC or at least on T cell.
  • the method comprises depleting cells expressing CD14 and/or CD25 and/or CD19 from a biological sample, thereby obtaining a CD14 and/or CD25 and/or CD19 cell depleted sample.
  • the method comprises incubating a CD14 and/or CD25 and/or CD19 cell depleted sample with FLT3L for a first time period.
  • the method comprises incubating at least one peptide with a CD14 and/or CD25 and/or CD19 cell depleted sample for a second time period, thereby obtaining a first matured APC peptide loaded sample.
  • the NEO-STIM process can comprise methods of preparing antigen activated (e.g., RAS activated) T cells using antigen loaded APCs.
  • the antigen loaded APC (APC) prepared by the methods described above is incubated with T cells to obtain antigen activated T cells.
  • the method can comprise generating at least one antigen specific T cell where the antigen is an antigen derived from a cancer cell.
  • the generating at least one antigen specific T cell comprises generating a plurality of antigen specific T cells.
  • the T cells are obtained from a biological sample from a subject.
  • the T cells are obtained from a biological sample from the same subject from whom the APCs are derived. In some embodiments, the T cells are obtained from a biological sample from a different subject than the subject from whom the APCs are derived. [0739] In some embodiments, the APCs and/or T cells are derived from a biological sample which is peripheral blood mononuclear cells (PBMC). In some embodiments, the APCs and/or T cells are derived from a biological sample which is a leukapheresis sample. [0740] In some embodiments, the APC comprises a dendritic cell (DC).
  • DC dendritic cell
  • the APC is derived from a CD14+ monocyte, or is a CD14 enriched APC, or is a CD141 enriched APC.
  • the CD14+ monocyte is enriched from a biological sample from a subject comprising peripheral blood mononuclear cells (PBMCs).
  • PBMCs peripheral blood mononuclear cells
  • the APC is PBMC.
  • the PBMC is freshly isolated PBMC.
  • the PBMC is frozen PBMC.
  • the PBMC is autologous PBMC isolated from the subject or the patient.
  • the PBMC is loaded with antigens, where the antigens can be peptides or polypeptides or polynucleotides, such as mRNA, that encode the peptides and polypeptides.
  • PBMCs monoocytes, DCs phagocytic cells
  • Peptides or polypeptides loaded on the PBMCs can be supplemented with adjuvants to increase immunogenicity.
  • the PBMC is loaded with nucleic acid antigens. Nucleic acid antigens can be in the form of mRNA, comprising sequences encoding one or more antigens.
  • mRNA antigen loading does not require adjuvant supplementation, because, for example, RNA can act as a self-adjuvant.
  • PBMCs are directly isolated or thawed from a frozen sample, and subjected to incubating with one or more antigens.
  • the PBMC sample is not further cultured for differentiation or subjected to further maturation of one or more cell components within the PBMC, (for example, maturation of antigen-presenting cells, or differentiation of monocytes to dendritic cells), before exposing the PBMCs to one or more antigens or nucleic acid encoding the one or more antigens.
  • one or more cell types are depleted or removed from the freshly isolated PBMC cell population or a freshly thawed PBMC population before exposing or incubating the cells to one or more antigens or nucleic acid encoding the one or more antigens.
  • CD14+ cells are depleted from the PBMC.
  • CD25+ cells are depleted from the PBMC.
  • CD11b+ cells are depleted from the PBMC.
  • the CD14+ and CD25+ cells are depleted from the PBMCs, before incubating with one or more antigens or one or more nucleic acids encoding the one or more antigens.
  • the CD11b+, and/or the CD14+ and/or CD25+ cells are depleted from the PBMC.
  • a method provided herein comprises preparing antigen-specific T cells by depleting CD14+ cells and/or CD25+ cells from a PBMC sample from a human subject containing about the same percentage of immature dendritic cells (DCs) as the percentage of immature DCs in the peripheral blood of the human subject.
  • a method provided herein comprises preparing antigen-specific T cells by depleting CD14+ cells and/or CD25+ cells from a PBMC sample from a human subject containing about the same percentage of mature DCs as the percentage of mature DCs in the peripheral blood of the human subject.
  • a method provided herein comprises preparing antigen-specific T cells by depleting CD14+ cells and/or CD25+ cells from a PBMC sample from a human subject containing about the same ratio of immature DCs to mature DCs as the ratio of immature DCs to mature DCs in the peripheral blood of the human subject.
  • a method provided herein comprises preparing antigen-specific T cells by depleting CD14+ cells and/or CD25+ cells from a PBMC sample from a human subject that has not been subject to a step of maturing immature DCs into mature DCs.
  • the antigen is from a cancer cell.
  • the CD14+ monocyte is stimulated with one or more cytokines or growth factors.
  • one or more cytokines or growth factors comprise GM-CSF, IL-4, FLT3L, TNF- ⁇ , IL-1 ⁇ , PGE1, IL-6, IL-7, IL-15, IFN- ⁇ , IFN- ⁇ , R848, LPS, ss-rna40, poly I:C, or a combination thereof.
  • the CD14+ monocyte is from a second biological sample comprising PBMCs.
  • the second biological sample is from the same subject.
  • the biological sample comprises peripheral blood mononuclear cells (PBMCs).
  • PBMCs peripheral blood mononuclear cells
  • the at least one antigen-specific T cell is stimulated in a medium comprising IL-7, IL-15, an indoleamine 2,3-dioxygenase-1 (IDO) inhibitor, an anti-PD-1 antibody, IL-12, or a combination thereof.
  • IDO inhibitor is epacadostat, navoximod, 1-methyltryptophan, or a combination thereof.
  • the subject is administered FLT3L prior to obtaining the biological sample for preparing the APCs and/or T cells.
  • the T cells are obtained from a biological sample from a subject as described in the previous sections of this disclosure.
  • the biological sample is freshly obtained from a subject or is a frozen sample.
  • the incubating is in presence of at least one cytokine or growth factor, which comprises GM-CSF, IL-4, FLT3L, TNF- ⁇ , IL-1 ⁇ , PGE1, IL-6, IL-7, IL-15, IFN- ⁇ , IFN- ⁇ , IL- 15, R848, LPS, ss-rna40, poly I:C, or any combination thereof.
  • cytokine or growth factor which comprises GM-CSF, IL-4, FLT3L, TNF- ⁇ , IL-1 ⁇ , PGE1, IL-6, IL-7, IL-15, IFN- ⁇ , IFN- ⁇ , IL- 15, R848, LPS, ss-rna40, poly I:C, or any combination thereof.
  • a method comprises stimulating T cells with IL-7, IL-15, or a combination thereof. In some embodiments, a method comprises stimulating T cells with IL-7, IL-15, or a combination thereof, in the presence of an IDO inhibitor, a PD-1 antibody or IL-12. In some embodiments, the stimulated T cell is expanded in presence of the one or more antigen epitope WSGR Docket No.50401-795.601 sequence or APCs loaded with the one or more antigen or epitope sequence, or APCs loaded with (e.g.
  • nucleic acid sequences such as mRNA sequences
  • one or more cytokines or growth factors comprise GM-CSF, IL-4, FLT3L, TNF- ⁇ , IL-1 ⁇ , PGE1, IL-6, IL-7, IL-15, IFN- ⁇ , IFN- ⁇ , R848, LPS, ss-rna40, poly I:C, or a combination thereof, FLT3L, under suitable T cell growth conditions ex vivo.
  • the method further comprises administering the antigen specific T cells to a subject.
  • the method comprises incubating the APC prepared as described in the previous sections with T cells in presence of a medium comprising the at least one cytokines or growth factor to generate antigen activated T cells.
  • the incubating comprises incubating a first APC preparation of the APC preparations to the T cells for more than 7 days.
  • the incubated T cells are stimulated T cells that expand in vitro on presence of the APC preparation, cytokines and growth factors for more than 7 days.
  • the incubating comprises incubating a first APC preparation of the APC preparations to the T cells for more than 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 days.
  • the first time period of the one or more time periods is about 1, 23, 4, 5, 6, 7, 8, or 9 days.
  • a total time period of the separate time periods is less than 28 days.
  • a total time period of the separate time periods is from 20-27 days.
  • a total time period of the separate time periods is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, or 39 days.
  • a method comprises incubating a first APC preparation of the APC preparations with the T cells for more than 7 days.
  • a method comprises incubating a first APC preparation of the APC preparations with the T cells for more than 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 days. In some embodiments, a method comprises incubating a first APC preparation of the APC preparations with the T cells for from 7-20, 8-20, 9-20, 10-20, 11- 20, or 12-20 days. In some embodiments, a method comprises incubating a first APC preparation of the APC preparations with the T cells for about 10-15 days. [0764] In some embodiments, a method comprises incubating a second APC preparation of the APC preparations to the T cells for 5-9 days.
  • a method comprises incubating a second APC preparation of the APC preparations to the T cells for 5, 6, 7, 8, or 9 days. In some embodiments, the method further comprises removing the one or more cytokines or growth factors of the second medium after the third time period and before a start of the fourth time period.
  • WSGR Docket No.50401-795.601 [0765]
  • a method comprises incubating a third APC preparation of the APC preparations to the T cells for 5-9 days. In some embodiments, the method comprises incubating a third APC preparation of the APC preparations to the T cells for 5, 6, 7, 8, or 9 days.
  • the method comprises incubating a first APC preparation of the APC preparations with the T cells for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 days, incubating a second APC preparation of the APC preparations to the T cells for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 days, and incubating a third APC preparation of the APC preparations to the T cells for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 days.
  • the method is performed ex vivo.
  • the T cells are cultured in a medium containing a cytokine.
  • an example of cytokines includes IL-7.
  • an example of cytokines includes IL-15.
  • an example of cytokines includes IL-7 and IL-15.
  • the T cells are cultured in a medium comprising IL-7, and/or IL-15.
  • the cytokine in a T cell culture or a medium has a final concentration of at least 0.05 ng/mL, 0.1 ng/mL, 0.2 ng/mL, 0.3 ng/mL, 0.4 ng/mL, 0.5 ng/mL, 0.8 ng/mL, 1 ng/mL, 2 ng/mL, 3 ng/mL, 4 ng/mL, 5 ng/mL, 6 ng/mL, 7 ng/mL, 8 ng/mL, 9 ng/mL, 10 ng/mL, 12 ng/mL, 15 ng/mL, 18 ng/mL, or 20 ng/mL.
  • the IL-7 in a T cell culture or a medium has a final concentration of at least 0.05 ng/mL, 0.1 ng/mL, 0.2 ng/mL, 0.3 ng/mL, 0.4 ng/mL, 0.5 ng/mL, 0.8 ng/mL, 1 ng/mL, 2 ng/mL, 3 ng/mL, 4 ng/mL, 5 ng/mL, 6 ng/mL, 7 ng/mL, 8 ng/mL, 9 ng/mL, 10 ng/mL, 12 ng/mL, 15 ng/mL, 18 ng/mL, or 20 ng/mL.
  • the IL-15 in a T cell culture or a medium has a final concentration of at least 0.05 ng/mL, 0.1 ng/mL, 0.2 ng/mL, 0.3 ng/mL, 0.4 ng/mL, 0.5 ng/mL, 0.8 ng/mL, 1 ng/mL, 2 ng/mL, 3 ng/mL, 4 ng/mL, 5 ng/mL, 6 ng/mL, 7 ng/mL, 8 ng/mL, 9 ng/mL, 10 ng/mL, 12 ng/mL, 15 ng/mL, 18 ng/mL, or 20 ng/mL.
  • the T cells are cultured in a medium further containing FLT3L.
  • the FLT3L in a T cell culture or a medium has a final concentration of in a T cell culture or a medium has a final concentration of at least 1 ng/mL, 2 ng/mL, 3 ng/mL, 4 ng/mL, 5 ng/mL, 6 ng/mL, 7 ng/mL, 8 ng/mL, 9 ng/mL, 10 ng/mL, 12 ng/mL, 15 ng/mL, 18 ng/mL, 20 ng/mL, 30 ng/mL, 40 ng/mL, 50 ng/mL, 60 ng/mL, 70 ng/mL, 80 ng/mL, 90 ng/mL, 100 ng/mL, or 200 ng/mL.
  • the T cells are incubated, induced, or stimulated in a medium containing FLT3L for a first period time. In some embodiments, the T cells are incubated, induced, or stimulated in a medium containing additionally added FLT3L for a second period time. In some embodiments, the T cells are incubated, induced, or stimulated in a medium containing additional added FLT3L for a third period time. In some embodiments, the T cells are incubated, induced, or stimulated in a medium containing additional added FLT3L for a fourth, a fifth, or a sixth period time, with freshly added FLT3L in each time period.
  • the T cells are cultured in presence of an antigen, e.g., an antigen presented by an APC, wherein the media comprises high potassium [K]+ content.
  • the T cells are cultured in presence of high [K]+ content in the media for at least a period of time during the incubation with APCs or T cells.
  • the [K]+ content in the media is altered for at least a period of time during the incubation with APCs or T cells.
  • the content in the media is kept constant over the period of T cell ex vivo culture.
  • the [K]+ content in the T cell culture medium is ⁇ 5 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 6 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 7 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 8 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 9 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 10 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 11 mM.
  • the [K]+ content in the T cell culture medium is ⁇ 12 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 13 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 14 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 15 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 16 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 17 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 18 mM.
  • the [K]+ content in the T cell culture medium is ⁇ 19 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 20 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 22 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 25 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 30 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 35 mM. In some embodiments, the [K]+ content in the T cell culture medium is ⁇ 40 mM.
  • the [K]+ content in the T cell culture medium is about 40 mM. [0769] In some embodiments, the [K]+ content in the T cell culture medium is about 40 mM for at least a period of time during the incubation of T cells with antigen.
  • the antigen can be presented by the antigen loaded APCs.
  • the T cells in the presence of [K]+ are tested for T effector functions, CD8+ cytotoxicity, cytokine production, and for memory phenotype. In some embodiments, T cells are grown in the presence of high [K]+ express effector T cell phenotype. In some embodiments, T cells grown in presence of high [K]+ express memory cell marker.
  • T cells grown in presence of high [K]+ do not express T cell exhaustion markers.
  • the stimulated T cell is a population of immune cells comprising the activated T cells stimulated with APCs comprising an antigenic peptide-MHC complex.
  • a method can comprise incubating a population of immune cells from a biological sample with APCs comprising a peptide-MHC complex, thereby obtaining a stimulated immune cell sample; determining expression of one or more cell markers of at least one immune cell of the stimulated immune cell sample; and determining binding of the at least one immune cell of the stimulated immune cell sample to a peptide-MHC complex; wherein determining expression of certain cell surface markers or other determinant markers, such as intracellular factors, or released agents, such as cytokines etc., and determining binding to the antigen-MHC complex are performed simultaneously.
  • the one or more cell markers comprise TNF- ⁇ , IFN- ⁇ , LAMP- 1, 4-1BB, IL-2, IL-17A, Granzyme B, PD-1, CD25, CD69, TIM3, LAG3, CTLA-4, CD62L, CD45RA, CD45RO, FoxP3, or any combination thereof.
  • the one or more cell markers comprise a cytokine.
  • the one or more cell markers comprise a degranulation marker.
  • the one or more cell markers comprise a cell-surface marker.
  • the one or more cell markers comprise a protein.
  • determining binding of the at least one immune cell of the stimulated immune cell sample to the peptide-MHC complex comprises determining binding of the at least one immune cell of the stimulated immune cell sample to an MHC tetramer comprising the peptide and the MHC of the peptide-MHC complex.
  • the MHC is a class I MHC or a class II MHC.
  • the peptide-MHC complex comprises one or more labels. [0771]
  • activation of T cell is verified by detecting the release of a cytokine by the activated T cell.
  • the cytokine is one or more of: TNF- ⁇ , IFN- ⁇ , IL-2, or IL- 18.
  • the activation of T cell is verified by its specific antigen binding and cytokine release. In some embodiments, the activation of T cells is verified by its ability to kill infected cells in vitro. A sample of activated T cells can be used to verify the activation status of the T cells. In some embodiments, a sample from the T cells is withdrawn from the T cell culture to determine the cellular composition and activation state by flow cytometry.
  • a percentage of the at least one antigen specific T cell in the composition is at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of total T cells or total immune cells.
  • the percentage of the at least one antigen specific T cell in the composition is about 5%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 7%.
  • the percentage of the at least one antigen specific T cell in the composition is about 10%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 12%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 15%. In some embodiments, the percentage of the at least one antigen WSGR Docket No.50401-795.601 specific T cell in the composition is about 20%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 25%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 30%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 40%.
  • the percentage of the at least one antigen specific T cell in the composition is about 50%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 60%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 70%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 80%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 90%.
  • a percentage of at least one antigen specific CD8+ T cell in the composition is at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 5%.
  • the percentage of the at least one antigen specific CD8+ T cells in the composition is about 7%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 10%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 12%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 15%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 20%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 25%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 30%.
  • the percentage of the at least one antigen specific CD8+ T cells in the composition is about 40%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 50%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 60%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 70% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells.
  • a percentage of the at least one antigen specific T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells.
  • a percentage of at least one antigen specific CD8+ T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells.
  • a percentage of at least one antigen specific CD4+ T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells.
  • the antigen is an overexpressed antigen, a viral antigen, a bacterial antigen, a protozoan antigen, a helminth antigen, or a combination thereof.
  • the number of at least one antigen specific CD8+ T cell in the composition is at least about 1x10 ⁇ 6, 2x10 ⁇ 6, 5x10 ⁇ 6, 1x10 ⁇ 7, 2x10 ⁇ 7, 5x10 ⁇ 7, 1x10 ⁇ 8, 2x10 ⁇ 8, or 5x10 ⁇ 8, antigen specific CD8+ T cells.
  • a number of at least one antigen specific CD4+ T cell in the composition is at least about 1x10 ⁇ 6, 2x10 ⁇ 6, 5x10 ⁇ 6, 1x10 ⁇ 7, 2x10 ⁇ 7, 5x10 ⁇ 7, 1x10 ⁇ 8, 2x10 ⁇ 8, or 5x10 ⁇ 8, antigen specific CD4+ T cells.
  • Method of T cell Manufacturing Provided herein are methods for antigen specific T cell manufacturing.
  • methods of preparing T cell compositions such as therapeutic T cell compositions.
  • a method can comprise expanding or inducing antigen specific T cells.
  • Preparing (e.g., inducing or expanding) T cells can also refer to manufacturing T cells, and broadly encompasses procedures to isolate, stimulate, culture, induce, and/or expand any type of T cells (e.g., CD4+ T cells and CD8+ T cells).
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprising incubating an APC with a population of immune cells from a biological sample depleted of cells expressing CD14 and/or CD25.
  • the method comprises preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating an APC with a population of immune cells from a biological sample depleted of cells expressing CD11b and/or CD19.
  • the WSGR Docket No.50401-795.601 method comprises incubating an APC with a population of immune cells from a biological sample depleted of cells expressing any CD11b and/or CD19 and/or CD14 and/or CD25 or any combination thereof.
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating an FMS-like tyrosine kinase 3 receptor ligand (FLT3L)-stimulated APC with a population of immune cells from a biological sample.
  • TCR T-cell receptor
  • FLT3L FMS-like tyrosine kinase 3 receptor ligand
  • a method of preparing a pharmaceutical composition comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising: incubating FMS-like tyrosine kinase 3 receptor ligand (FLT3L) with a population of immune cells from a biological sample for a first time period; and thereafter incubating at least one T cell of the biological sample with an APC.
  • TCR T-cell receptor
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods of less than 28 days from incubating the population of immune cells with a first APC preparation of the one or more APC preparations, wherein at least one antigen specific memory T cell is expanded, or at least one antigen specific na ⁇ ve T cell is induced.
  • TCR T-cell receptor
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating a population of immune cells from a biological sample with 3 or less APC preparations for 3 or less separate time periods, wherein at least one antigen specific memory T cell is expanded or at least one antigen specific na ⁇ ve T cell is induced.
  • TCR T-cell receptor
  • a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods, thereby stimulating T cells to become antigen specific T cells, wherein a percentage of antigen specific T cells is at least about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of total CD4+ T cells, total CD8+ T cells,
  • a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with 3 or less APC preparations for 3 or less WSGR Docket No.50401-795.601 separate time periods, thereby stimulating T cells to become antigen specific T cells.
  • a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with 2 or less APC preparations for 2 or less separate time periods, thereby stimulating T cells to become antigen specific T cells.
  • a method that comprises incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods, thereby stimulating T cells to become antigen specific T cells, wherein the APC preparation is a PBMC cell population from which cells expressing one or more cell surface markers are depleted prior to antigen loading of the APC population.
  • the APC preparation is a PBMC cell population from which cells expressing one or more cell surface markers are depleted prior to antigen loading of the APC population.
  • CD14+ cells are depleted prior to antigen loading of an APC population.
  • CD25+ cells are depleted prior to antigen loading of an APC population.
  • CD11b+ cells are depleted prior to antigen loading of an APC population.
  • CD19+ cells are depleted prior to antigen loading of an APC population.
  • CD3+ cells are depleted prior to antigen loading of an APC population.
  • CD25+ cells and CD14+ cells are depleted prior to antigen loading of an APC population.
  • CD11b+ and CD25+ cells are depleted prior to antigen loading of an APC population.
  • CD11b+ and CD14+ cells are depleted prior to antigen loading of an APC population.
  • CD11b+, CD14+ and CD25+ cells are depleted prior to antigen loading of an APC population.
  • CD11b+, and CD19+ cells are depleted prior to antigen loading of an APC population.
  • CD11b+, CD19+ and CD25+ cells are depleted prior to antigen loading of an APC population.
  • CD11b+, CD14+, CD19+ and CD25+ cells are depleted prior to antigen loading of an APC population.
  • the method comprises adding to any of the depleted APC population described above, an APC enriched cell PBMC-derived population that are depleted of CD3+ cell.
  • the APC enriched cell PBMC-derived population is depleted of CD3+ and cells depleted of any one or more of CD11b+, CD14+, CD19+, or CD25+.
  • a biological sample comprises peripheral blood mononuclear cells (PBMCs).
  • the method comprises adding to a PBMC sample, a composition comprising one or more antigenic peptides or nucleic acids encoding the same, thereby loading the APCs within the PBMCs with antigens for antigen presentation to T cells in the PBMC.
  • a method comprises: (a) obtaining a biological sample from a subject comprising at least one antigen-presenting cell (APC); (b) enriching cells expressing CD11c from the biological sample, thereby obtaining a CD11c+ cell enriched sample; (c) incubating the CD11c+ cell enriched sample with at least one cytokine or growth factor for a first time period; (d) incubating at WSGR Docket No.50401-795.601 least one peptide with the CD11c+ enriched sample of (c) for a second time period, thereby obtaining an APC peptide loaded sample; (e) incubating the APC peptide loaded sample with one or more cytokines or growth factors for a third time period, thereby obtaining a matured APC sample; (f) incubating APCs of the matured APC sample with a CD11b and/or CD14 and/or CD25 depleted sample comprising PBMCs for a fourth time
  • a method comprises: (a) obtaining a biological sample from a subject comprising at least one antigen-presenting cell (APC); (b) enriching cells expressing CD14 from the biological sample, thereby obtaining a CD14+ cell enriched sample; (c) incubating the CD14+ cell enriched sample with at least one cytokine or growth factor for a first time period; (d) incubating at least one peptide with the CD14+ enriched sample of (c) for a second time period, thereby obtaining an APC peptide loaded sample; (e) incubating the APC peptide loaded sample with one or more cytokines or growth factors for a third time period, thereby obtaining a matured APC sample; (f) incubating APCs of the matured APC sample with a CD14 and/or CD25 depleted sample comprising PBMCs for a fourth time period; (g) incubating the PBMCs with APCs of a matured APC
  • a method comprises: (a) obtaining a biological sample from a subject comprising at least one APC and at least one PBMC; (b) depleting cells expressing CD11b and/or CD19 from the biological sample, thereby obtaining a CD11b and/or CD19 cell depleted sample; (c) incubating the CD11b and/or CD19 cell depleted sample with FLT3L for a first time period; (d) incubating at least one peptide with the CD11b and/or CD19 cell depleted sample of (c) for a second time period, thereby obtaining an APC peptide loaded sample; (e) incubating the APC peptide loaded sample with the at least one PBMC for a third time period, thereby obtaining a first stimulated PBMC sample; (f) incubating a PBMC of the first stimulated PBMC sample with an APC of a matured APC sample for a fourth time period, thereby obtaining a
  • a method comprises: (a) obtaining a biological sample from a subject comprising at least one APC and at least one PBMC; (b) depleting cells expressing CD11b and/or CD19 and/or CD14 and/or CD25 from the biological sample, thereby obtaining a CD11b and/or CD19 cell depleted sample; (c) incubating the CD11b and/or CD19 and/or CD14 and/or CD25 cell WSGR Docket No.50401-795.601 depleted sample with FLT3L for a first time period; (d) incubating at least one peptide with the CD11b and/or CD19 and/or CD14 and/or CD25 cell depleted sample of (c) for a second time period, thereby obtaining an APC peptide loaded sample; (e) incubating the APC peptide loaded sample with the at least one PBMC for a third time period, thereby obtaining a first stimulated PBMC sample; (a) obtaining a biological sample
  • a method comprises: (a) obtaining a biological sample from a subject comprising at least one APC and at least one PBMC; (b) depleting cells expressing CD14 and/or CD25 from the biological sample, thereby obtaining a CD14 and/or CD25 cell depleted sample; (c) incubating the CD14 and/or CD25 cell depleted sample with FLT3L for a first time period; (d) incubating at least one peptide with the CD14 and/or CD25 cell depleted sample of (c) for a second time period, thereby obtaining an APC peptide loaded sample; (e) incubating the APC peptide loaded sample with the at least one PBMC for a third time period, thereby obtaining a first stimulated PBMC sample; (f) incubating a PBMC of the first stimulated PBMC sample with an APC of a matured APC sample for a fourth time period, thereby obtaining a second stimulated
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating an APC with a population of immune cells from a biological sample depleted of cells expressing CD14 and/or CD25.
  • TCR T-cell receptor
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods of less than 28 days from incubating the population of immune cells with a first APC preparation of the one or more APC preparations, wherein at least one antigen specific memory T cell is expanded, or at least one antigen specific na ⁇ ve T cell is induced.
  • TCR T-cell receptor
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating a population of immune cells from a biological sample with 3 or WSGR Docket No.50401-795.601 less APC preparations for 3 or less separate time periods, wherein at least one antigen specific memory T cell is expanded or at least one antigen specific na ⁇ ve T cell is induced.
  • TCR T-cell receptor
  • a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises contacting a population of immune cells (e.g., PBMCs) to APCs.
  • a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells (e.g., PBMCs) with APCs for a time period.
  • the population of immune cells is from a biological sample.
  • the population of immune cells is from a sample (e.g., a biological sample) depleted of CD14 expressing cells.
  • the population of immune cells is from a sample (e.g., a biological sample) depleted of CD25 expressing cells. In some embodiments, the population of immune cells is from a sample (e.g., a biological sample) depleted of CD14 expressing cells and CD25 expressing cells.
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating an FMS- like tyrosine kinase 3 receptor ligand (FLT3L)-stimulated APC with a population of immune cells from a biological sample.
  • TCR T-cell receptor
  • a method of preparing a pharmaceutical composition comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising: incubating FMS-like tyrosine kinase 3 receptor ligand (FLT3L) with a population of immune cells from a biological sample for a first time period; and thereafter incubating at least one T cell of the biological sample with an APC.
  • TCR T-cell receptor
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises contacting a population of immune cells from a sample (e.g., a biological sample) with FMS-like tyrosine kinase 3 receptor ligand (FLT3L).
  • a sample e.g., a biological sample
  • FMS-like tyrosine kinase 3 receptor ligand FMS-like tyrosine kinase 3 receptor ligand
  • a method of preparing at least one antigen specific T cell comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises contacting a population of immune cells from a sample (e.g., a biological sample) with FMS-like tyrosine kinase 3 receptor ligand (FLT3L)-stimulated APCs.
  • TCR T-cell receptor
  • FLT3L FMS-like tyrosine kinase 3 receptor ligand
  • TCR T-cell receptor
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises contacting a population of immune cells from a sample (e.g., a biological sample) to one or more APC preparations.
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a sample (e.g., a biological sample) to one or more APC preparations for one or more separate time periods.
  • a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a sample (e.g., a biological sample) to one or more APC preparations for 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 separate time periods.
  • the one or more separate time periods is less than 28 days calculated from incubating the population of immune cells with a first APC preparation of the one or more APC preparations.
  • a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells to APCs for a time period, wherein the population of immune cells is from a biological sample comprising PBMCs.
  • a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells to APCs for a time period, wherein the population of immune cells is from a biological sample depleted of CD14 and/or CD25 expressing cells.
  • a method of preparing antigen specific T cells comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with FMS-like tyrosine kinase 3 receptor ligand (FLT3L)- stimulated APCs for a time period.
  • TCR T-cell receptor
  • TCR T-cell receptor
  • a method of preparing antigen specific T cells comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods, thereby inducing or expanding antigen specific T cells, wherein the one or more separate time periods is less than 28 days calculated from incubating the population of immune cells with a WSGR Docket No.50401-795.601 first APC preparation of the one or more APC preparations.
  • TCR T-cell receptor
  • incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods is performed in a medium containing IL-7, IL-15, or a combination thereof.
  • the medium further comprises an indoleamine 2,3-dioxygenase-1 (IDO) inhibitor, an anti-PD-1 antibody, IL-12, or a combination thereof.
  • IDO indoleamine 2,3-dioxygenase-1
  • the IDO inhibitor can be epacadostat, navoximod, 1-Methyltryptophan, or a combination thereof.
  • the IDO inhibitor can increase the number of antigen-specific CD8+ cells.
  • the IDO inhibitor can maintain the functional profile of memory CD8+ T cell responses.
  • the PD-1 antibody can increase the absolute number of antigen-specific memory CD8+ T cell responses.
  • the PD-1 antibody can increase proliferation rate of the cells treated with such antibody.
  • the additional of IL- 12 can result in an increase of antigen-specific cells and/or an increase in the frequency of CD8+ T cells.
  • a method of preparing antigen specific T cells comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells comprising from a biological sample with one or more APC preparations for one or more separate time periods, thereby expanding or inducing antigen specific T cells, wherein a percentage of antigen specific T cells, antigen specific CD4+ T cells, or antigen specific CD8+ T cells is at least about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%,
  • a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with 3 or less APC preparations for 3 or less separate time periods, thereby stimulating T cells to become antigen specific T cells.
  • the population of immune cells is from a biological sample depleted of CD14 and/or CD25 expressing cells.
  • the APCs are FMS-like tyrosine kinase 3 receptor ligand (FLT3L)-stimulated APCs.
  • the APCs comprise one or more APC preparations.
  • the APC preparations comprise 3 or less APC preparations. In some embodiments, the APC preparations are incubated with the immune cells sequentially within one or more separate time periods.
  • the biological sample is from a subject. In some embodiments, the subject is a human. For example, the subject can be a patient or a donor. In some embodiments, the subject has a disease or disorder. In some embodiments, the disease or disorder is cancer.
  • the antigen specific T cells comprise CD4+ and/or CD8+ T cells. In some WSGR Docket No.50401-795.601 embodiments, the antigen specific T cells comprise CD4 enriched T cells and/or CD8 enriched T cells.
  • a CD4+ T cell and/or CD8+ T cell can be isolated from, enriched from, or purified from a biological sample from a subject comprising PBMCs.
  • the antigen specific T cells are na ⁇ ve CD4+ and/or na ⁇ ve CD8+ T cells.
  • the antigen specific T cells are memory CD4+ and/or memory CD8+ T cells.
  • each of the at least one antigen peptide sequence binds to a protein encoded by an HLA allele expressed by the subject. In some embodiments, each of the at least one antigen peptide sequence is not present in non-cancer cells of the subject.
  • each of the at least one antigen peptide sequences is encoded by genome of a cancer cell. In some embodiments, one or more of the at least one antigen peptide sequence has a length of from 8-50 naturally occurring amino acids. In some embodiments, the at least one antigen peptide sequence comprises a plurality of antigen peptide sequences. In some embodiments, the plurality of antigen peptide sequences comprises from 2-50, 3-50, 4-50, 5-5-, 6-50, 7-50, 8-50, 9-50, or 10-50 antigen peptide sequences. [0809] In some embodiments, the APCs comprise APCs loaded with one or more antigen peptides comprising one or more of the at least one antigen peptide sequence.
  • the APCs are autologous APCs or allogenic APCs. In some embodiments, the APCs comprise dendritic cells (DCs).
  • a method comprises depleting CD14 and/or CD25 expressing cells from the biological sample. In some embodiments, depleting CD14+ cells comprises contacting a CD14 binding agent to the APCs. In some embodiments, the APCs are derived from CD14+ monocytes. In some embodiments, the APCs are enriched from the biological sample. For example, an APC can be isolated from, enriched from, or purified from a biological sample from a subject comprising PBMCs.
  • the APCs are stimulated with one or more cytokines or growth factors.
  • the one or more cytokines or growth factors comprise GM-CSF, IL-4, FLT3L, or a combination thereof.
  • the one or more cytokines or growth factors comprise IL-4, IFN- ⁇ , LPS, GM-CSF, TNF- ⁇ , IL-1 ⁇ , PGE1, IL-6, IL-7 or a combination thereof.
  • the APCs are from a second biological sample. In some embodiments, the second biological sample is from the same subject.
  • a percentage of antigen specific T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells.
  • a percentage of antigen specific T cells in the method is from about 0.1% to about 5%, from about 5 % to 10%, from about 10% to 15%, from about 15% to 20%, from about 20% to 25%, from about 25% to 30%, from about 30% to 35%, WSGR Docket No.50401-795.601 from about 35% to about 40%, from about 40% to about 45%, from about 45% to about 50%, from about 50% to about 55%, from about 55% to about 60%, from about 60% to 65%, or from about 65% to about 70% of total T cells or total immune cells.
  • a percentage of antigen specific CD8+ T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells.
  • a percentage of antigen specific na ⁇ ve CD8+ T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells.
  • a percentage of antigen specific memory CD8+ T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells.
  • a percentage of antigen specific CD4+ T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells.
  • a percentage of antigen specific CD4+ T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells.
  • a percentage of antigen specific T cells in the biological sample is at most about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%.
  • a percentage of antigen specific CD8+ T cells in the biological sample is at most about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%.
  • a percentage of antigen specific na ⁇ ve CD8+ T cells in the biological sample is at most about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%.
  • a percentage of antigen specific memory CD8+ T cells in the biological sample is at most about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%.
  • a percentage of antigen specific CD4+ T cells in the biological sample is at most about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%.
  • a biological sample is freshly obtained from a subject or is a frozen sample.
  • a method comprises incubating one or more of the APC preparations with a first medium comprising at least one cytokine or growth factor for a first time period.
  • the first time period is at lease 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17, or 18 days.
  • the first time period is no more than 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 days.
  • the first time period is at least 1, 23, 4, 5, 6, 7, 8, or 9 days.
  • the first time period is no more than 3, 4, 5, 6, 7, 8, 9, or 10 days.
  • the at least one cytokine or growth factor comprises GM-CSF, IL-4, FLT3L, TNF- ⁇ , IL-1 ⁇ , PGE1, IL-6, IL-7, IFN- ⁇ , LPS, IFN- ⁇ , R848, LPS, ss-rna40, poly I:C, or any combination thereof.
  • a method comprises incubating one or more of the APC preparations with at least one peptide for a second time period. In some embodiments, the second time period is no more than 1 hour.
  • a method comprises incubating one or more of the APC preparations with a second medium comprising one or more cytokines or growth factors for a third time period, thereby obtaining matured APCs.
  • the one or more cytokines or growth factors comprises GM-CSF (granulocyte macrophage colony-stimulating factor), IL-4, FLT3L, IFN- ⁇ , LPS, TNF- ⁇ , IL-1 ⁇ , PGE1, IL-6, IL-7, IFN- ⁇ , R848 (resiquimod), LPS, ss-rna40, poly I:C, CpG, or a combination thereof.
  • the third time period is no more than 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 days. In some embodiments, the third time period is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 days. In some embodiments, the third time period is no more than 2, 3, 4, or 5 days. In some embodiments, the third time period is at least 1, 2, 3, or 4 days. [0818] In some embodiments, the method further comprises removing the one or more cytokines or growth factors of the second medium after the third time period and before a start of the fourth time period.
  • the NEO-STIM process may comprise methods of generating antigen loaded PBMCs for induction of T cells (e.g., RAS-specific T cells).
  • the methods provided herein comprise isolating PBMCs from a human blood sample, and directly loading the PBMCs with antigens. PBMCs directly contacted with antigens can readily take up antigens by phagocytosis and present antigens to T cells that can be in the culture or added to the culture.
  • the methods provided herein comprise isolating PBMCs from a human blood sample, and nucleofecting or electroporating a polynucleotide, such as an mRNA, that encodes one or more antigens into the PBMCs.
  • antigens delivered to PBMCs instead of antigen-presenting cells maturing to DCs, provides a great advantage in terms of time and manufacturing efficiency.
  • the PBMCs can be further depleted of one or more cell types.
  • the PBMCs can be depleted of CD3+ cells for an initial period of antigen loading and the CD3+ cells returned to the culture for the PBMCs to stimulate the CD3+ T cells.
  • the PBMCs can be depleted of CD25+ cells. In some embodiments, the PBMCs can be depleted of CD14+ cells. In some embodiments, the PBMCs can be depleted of CD19+ cells. In some embodiments, the PBMCs can be depleted of both CD14 and CD25 expressing WSGR Docket No.50401-795.601 cells. In some embodiments, CD11b+ cells are depleted from the PBMC sample before antigen loading. In some embodiments, CD11b+ and CD25+ cells are depleted from the PBMC sample before antigen loading.
  • the PBMCs isolated from a human blood sample can be handled as minimally as possible prior to loading with antigens. Increased handling of PBMCs, for example freezing and thawing cells, multiple cell depletion steps, etc., can impair cell health and viability.
  • the PBMCs are allogeneic to the subject of therapy. In some embodiments the PBMCs are allogeneic to the subject of adoptive cell therapy with antigen specific T cells.
  • the PBMCs are HLA-matched for the subject of therapy.
  • the PBMCs are allogeneic, and matched for the subject’s HLA subtypes, whereas the CD3+ T cells are autologous.
  • the PBMCs are loaded with the respective antigens (e.g., derived from analysis of a peptide presentation analysis platform such as RECON), cocultured with subject’s PBMC comprising T cells in order to stimulate antigen specific T cells.
  • mRNA is used as the immunogen for uptake and antigen presenting.
  • the mRNA comprises shortmer constructs, encoding 9-10 amino acid peptides comprising an epitope. In some embodiments, the mRNA comprises longmer constructs, encoding bout 25 amino acid peptides. In some embodiments, the mRNA comprises a concatenation of multiple epitopes. In some embodiments, the concatemers can comprise one or more epitopes from the same antigenic protein. In some embodiments, the concatemers can comprise one or epitopes from several different antigenic proteins. Several embodiments are described in the Examples section.
  • Antigen loading of PBMCs by antigen loading can comprise various mechanisms of delivery ad incorporation of nucleic acid into the PBMCs.
  • the delivery or mechanism of incorporation includes transfection, electroporation, nucleofection, chemical delivery, for example, lipid encapsulated, or liposome mediated delivery.
  • Use of antigen loaded PBMCs to stimulate T cells can save the maturation time needed in a method that generates DCs from a PBMC sample prior to T cell stimulation.
  • use of antigen loaded PBMCs for example, mRNA loaded PBMCs as APCs reduces the total manufacturing time by 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days.
  • use of antigen loaded PBMCs as APCs reduces the total manufacturing time by 3 days. In some embodiments, use of antigen loaded PBMCs as APCs reduces the total manufacturing time by 4 days. In some embodiments, use of antigen loaded PBMCs as APCs reduces the total manufacturing time by 5 days. In some embodiments, use of antigen loaded PBMCs as APCs reduces the total manufacturing time WSGR Docket No.50401-795.601 by 6 days. In some embodiments, use of antigen loaded PBMCs as APCs reduces the total manufacturing time by 7 days.
  • mRNA loaded PBMCs can stimulate T cells and generate higher antigen specific T cells. In some embodiments, mRNA loaded PBMCs can stimulate T cells and generate higher yield of antigen specific T cells. In some embodiments, mRNA loaded PBMCs can stimulate T cells and generate antigen specific T cells that have higher representation of the input antigens, i.e., reactive to diverse antigens. In some embodiments, mRNA loaded PBMCs can stimulate T cells that have at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more antigen reactivity in the pool of expanded cells.
  • the mRNA loaded PBMCs can stimulate T cells that have at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more antigen reactivity than conventional antigen loaded APCs (such as peptide loaded DCs).
  • T-Cell Receptors [0827] Also disclosed herein are T cell receptors (TCRs) and recombinant nucleic acids encoding the same.
  • TCRs T cell receptors
  • recombinant nucleic acid encoding a TCR that recognizes epitopes (e.g., epitopes derived from RAS) derived from a protein encoded by a gene of a cancer cell.
  • the T-cell receptor can comprise a TCR beta chain construct and a TCR alpha chain construct.
  • TCR The ability of T cells to recognize antigens associated with infectious organisms or cancers is conferred by its TCR, which is made up of both an alpha ( ⁇ ) chain and a beta ( ⁇ ) chain or a gamma ( ⁇ ) and a delta ( ⁇ ) chain.
  • the proteins which make up these chains are encoded by DNA, which employs a unique mechanism for generating the diversity of the TCR.
  • This multi-subunit immune recognition receptor can associate with the CD3 complex and bind peptides presented by the MHC class I and II proteins on the surface of antigen-presenting cells (APCs).
  • APCs antigen-presenting cells

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Abstract

The present disclosure provides a therapy with vaccine compositions including multiepitopic polypeptides, recombinant nucleic acids encoding multiepitopic polypeptides and methods of use thereof. Also provided herein are T-cell receptors (TCRs) that can recognize one or more epitopes of the multiepitopic polypeptides. The therapy provided herein can comprise (i) a TCR, a recombinant nucleic acid encoding the TCR, or cells comprising the TCR or the recombinant nucleic acid encoding the TCR, and (ii) a vaccine composition described herein. The methods and compositions provided herein can be used for the treatment of cancer.

Description

WSGR Docket No.50401-795.601 RAS VACCINE COMPOSITIONS AND METHODS OF USE CROSS-REFERENCE [0001] This application claims the benefit of U.S. Provisional Application No.63/638,565, filed on April 25, 2024, which is incorporated herein by reference in its entirety. BACKGROUND [0002] Cancer is a leading cause of death worldwide, accounting for nearly one in six deaths globally. While cell-based immunotherapies have led to advances in treatment options for cancer, they are often limited in their long-term efficacy. There is a need for methods and compositions to improve the efficacy of cell-based immunotherapy. SUMMARY [0003] Provided herein is a method of treating a subject with a disease or condition comprising administering to the subject a therapy comprising (i) a multiepitopic polypeptide, (ii) a recombinant nucleic acid encoding the multiepitopic polypeptide, or (iii) a cell comprising the multiepitopic polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length RAS polypeptide and comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, wherein the first RAS epitope sequence and the second RAS epitope sequence are different, and wherein presentation of the first and/or second RAS epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the therapy is higher than the presentation of the first and/or second RAS epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. [0004] Also provided herein is a method of treating a subject with a disease or condition comprising administering to the subject a therapy comprising (i) a multiepitopic polypeptide, (ii) a recombinant nucleic acid encoding the multiepitopic polypeptide, or (iii) a cell comprising the multiepitopic polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length RAS polypeptide and comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, wherein the first RAS epitope sequence and the second RAS epitope sequence are different, and wherein the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker. [0005] In some embodiments, the full-length RAS polypeptide is a full-length KRAS, NRAS or HRAS polypeptide, wherein the first RAS amino acid sequence is a first KRAS, NRAS or HRAS WSGR Docket No.50401-795.601 amino acid sequence, and wherein the second RAS amino acid sequence is a second KRAS, NRAS or HRAS amino acid sequence. [0006] In some embodiments, the method of any one of the preceding embodiments further comprises administering the subject a T-cell receptor (TCR), a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR. [0007] In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence is separated by a linker. [0008] In some embodiments, the first RAS amino acid sequence is the first epitope sequence and/or the second RAS amino acid sequence is the second epitope sequence. [0009] In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation, and/or the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation. [0010] In some embodiments, the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C. [0011] In some embodiments, the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C. [0012] In some embodiments, the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell. [0013] In some embodiments, the first RAS mutation is G12V, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 58-62 and 65-72. [0014] In some embodiments, the first RAS mutation is G12D, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79. [0015] In some embodiments, the first RAS mutation is G12C, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096. [0016] In some embodiments, the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length RAS polypeptide. [0017] In some embodiments, the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length RAS polypeptide. [0018] In some embodiments, the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker. [0019] In some embodiments, the first RAS amino acid sequence comprises the first RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first RAS epitope sequence from the full-length RAS polypeptide. WSGR Docket No.50401-795.601 [0020] In some embodiments, the second RAS amino acid sequence comprises the second RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide. [0021] In some embodiments, the multiepitopic polypeptide does not comprise more than 12 or more consecutive amino acids from the full-length RAS polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length RAS polypeptide. [0022] In some embodiments, the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the first or the second RAS epitope sequence, and (ii) a human MHC encoded by an HLA allele. [0023] In some embodiments, the multiepitopic polypeptide is a RAS polypeptide comprising the first RAS epitope sequence and the second RAS epitope sequence. [0024] In some embodiments, the linker is a cleavable linker. [0025] Also provided herein is a method of treating a subject with a disease or condition comprising administering to the subject (a) a RAS polypeptide, (b) a recombinant nucleic acid encoding the RAS polypeptide, or (c) a cell comprising the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide, wherein the RAS polypeptide comprises a RAS epitope sequence, wherein the subject has been previously administered a T-cell receptor (TCR), a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS epitope sequence, and (ii) a human MHC encoded by an HLA allele. [0026] Also provided herein is a method of treating a subject with a disease or condition comprising administering to the subject a T-cell receptor (TCR), a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) a RAS epitope sequence, and (ii) a human MHC encoded by an HLA allele, wherein the subject has been previously administered (a) a RAS polypeptide, (b) a recombinant nucleic acid encoding the RAS polypeptide, or (c) a cell comprising the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide, wherein the RAS polypeptide comprises the RAS epitope sequence. [0027] Also provided herein is a method of treating a subject with a disease or condition comprising, administering to the subject (i) a RAS polypeptide, (ii) a recombinant nucleic acid encoding the RAS polypeptide, or (iii) a cell comprising the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide, wherein the RAS polypeptide comprises a RAS epitope sequence; and administering to the subject a TCR, a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes WSGR Docket No.50401-795.601 and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS peptide sequence, and (ii) a human MHC encoded by an HLA allele. [0028] In some embodiments, administering in (a) is performed concurrently with administering in (b). [0029] In some embodiments, administering in (a) is prior to administering in (b). [0030] In some embodiments, administering in (a) is subsequent to administering in (b). [0031] In some embodiments, the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years or more after the subject has been administered the TCR or the recombinant nucleic acid encoding the TCR. [0032] In some embodiments, the TCR or the recombinant nucleic acid encoding the TCR is administered at least 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years or more after the subject has been administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide. [0033] In some embodiments, the cell is an immune cell. [0034] In some embodiments, the T-cell receptor (TCR) or the recombinant nucleic acid encoding the TCR is expressed by an immune cell. [0035] In some embodiments, the TCR is a soluble TCR. [0036] In some embodiments, the method of any one of the preceding embodiments further comprises administering two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs, or cells comprising the two or more different TCRs or the recombinant nucleic acids encoding the two or more different TCRs and wherein the two or more different TCRs comprise a first TCR and a second TCR. [0037] In some embodiments, the two or more different TCRs are expressed on surface of two different immune cells. [0038] In some embodiments, the first TCR and the second TCR bind to different peptide:MHC complexes, each peptide:MHC complex comprising (i) an epitope sequence and (ii) a human MHC encoded by an HLA allele. [0039] In some embodiments, the two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs are administered separately or co-administered in a same mixture. [0040] In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12V mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA- C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, and the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12D WSGR Docket No.50401-795.601 mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA- B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA- A*68:01. [0041] In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12V mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA- C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, and the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12C mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA- DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. [0042] In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12D mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA- A*11:01, and HLA-A*68:01., and the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12C mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA- C*03:03. [0043] In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 58-62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75- 79 and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01; the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA- B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, and, HLA-A*03 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA- A*68:01, and HLA-C*03:03; or the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75-79 and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, WSGR Docket No.50401-795.601 HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. [0044] In some embodiments, the RAS polypeptide does not comprise a full-length RAS protein sequence. [0045] In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 59. [0046] In some embodiments, the HLA allele is selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*03:02, HLA-A*03:05, HLA-B*40:01, and HLA-A*68:01. [0047] In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 60. [0048] In some embodiments, the HLA allele is HLA-C*01:02. [0049] In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 61 or 62. [0050] In some embodiments, the HLA allele is HLA-C*03:03, or HLA-C*03:04. [0051] In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 59. [0052] In some embodiments, the MHC allele is HLA-A*11:01. [0053] In some embodiments, the RAS epitope sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 65-71. [0054] In some embodiments, the MHC allele is HLA-DRB1*07:01. [0055] In some embodiments, the RAS epitope sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 58 or 72. [0056] In some embodiments, the MHC allele is selected from the group consisting of HLA- A*03:01, HLA-A*03:02, and HLA-A*03:05. [0057] In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 75. [0058] In some embodiments, the MHC allele is selected from the group consisting of HLA- B*07:02, HLA-C*08:02, HLA-C*03:04, and HLA-C*05:01. [0059] In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 76. [0060] In some embodiments, the MHC allele is selected from the group consisting of HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01. [0061] In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 77. [0062] In some embodiments, the MHC allele is HLA-A*11:01. WSGR Docket No.50401-795.601 [0063] In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 78 or 79. [0064] In some embodiments, the MHC allele is HLA-C*08:02. [0065] In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 29. [0066] In some embodiments, the MHC allele is HLA-DRB1*11:01. [0067] In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 81 or 1096. [0068] In some embodiments, the MHC allele is selected from the group consisting of HLA-A*3:01, HLA-A*11:01, and HLA-A*68:01. [0069] In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 82. [0070] In some embodiments, the MHC allele is HLA-C*03:03. [0071] In some embodiments, the RAS polypeptide is a multiepitopic polypeptide, and wherein the multiepitopic polypeptide does not comprise a full-length RAS polypeptide and comprises two or more different RAS epitope sequences. [0072] In some embodiments, the multiepitopic polypeptide comprises at least 3, 4, 5, or more different RAS epitope sequences. [0073] In some embodiments, the two or more different RAS epitope sequences are separated by linker sequences. [0074] In some embodiments, antigen presenting cells (APCs) of the subject administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide comprising the multiepitopic polypeptide present more of a RAS epitope sequence as a peptide:MHC complex compared to the APCs of a subject administered a full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. [0075] In some embodiments, T cells of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide exhibit increased expansion compared to T cells of a subject administered a full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. [0076] In some embodiments, the multiepitopic polypeptide comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, and wherein the first RAS epitope sequence and the second RAS epitope sequence are different or wherein the first RAS amino acid sequence and the second RAS amino acid sequence comprise different RAS mutations. [0077] In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence is separated by a linker. WSGR Docket No.50401-795.601 [0078] In some embodiments, the first amino acid sequence is the first epitope sequence and/or the second amino acid sequence is the second epitope sequence. [0079] In some embodiments, the first amino acid sequence consists of the first epitope sequence, and/or the second amino acid sequence consists of the second epitope sequence. [0080] In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation, and/or the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation. [0081] In some embodiments, the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C. [0082] In some embodiments, the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C. [0083] In some embodiments, the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell. [0084] In some embodiments, the first RAS mutation is G12V, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72. [0085] In some embodiments, the first RAS mutation is G12D, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79. [0086] In some embodiments, the first RAS mutation is G12C, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096. [0087] In some embodiments, the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length RAS polypeptide. [0088] In some embodiments, the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length RAS polypeptide. [0089] In some embodiments, the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker. [0090] In some embodiments, the first amino acid sequence comprises the first RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first RAS epitope sequence from the full-length RAS polypeptide. [0091] In some embodiments, the second amino acid sequence comprises the second RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide. [0092] In some embodiments, the multiepitopic polypeptide does not comprise more than 12 or more consecutive amino acids from the full-length RAS polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length RAS polypeptide. WSGR Docket No.50401-795.601 [0093] In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence are presentable by different HLA alleles, are presented by different HLA alleles, bind to different HLA alleles, are predicted to bind to different HLA alleles, or are predicted to be presented by different HLA alleles. [0094] In some embodiments, a first RAS epitope sequence (i) binds to or is predicted to bind to a first HLA allele with a KD of less than 100 nM and (ii) to binds to or is predicted to bind to a second HLA allele with a KD of more than 500 nM. [0095] In some embodiments, the first amino acid sequence is operably linked to the second amino acid sequence via a linker. [0096] In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. [0097] In some embodiments, the multiepitopic polypeptide comprises a first amino acid sequence comprising a first RAS epitope sequence, operably linked to a second amino acid sequence comprising a second RAS epitope sequence, operably linked to a third amino acid sequence comprising a third RAS epitope sequence. [0098] In some embodiments, the first RAS epitope sequence, the second RAS epitope sequence, and/or the third RAS epitope sequence comprises a RAS mutation selected from the group consisting of G12V, G12D, and G12C, and wherein the first RAS epitope sequence, the second RAS epitope sequence, and the third RAS epitope sequence comprise different RAS mutations. [0099] In some embodiments, the first RAS epitope sequence comprises a G12V mutation. [0100] In some embodiments, the second RAS epitope sequence comprises a G12D mutation. [0101] In some embodiments, the third RAS epitope sequence comprises a G12C mutation. [0102] In some embodiments, (i) the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA- B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA- A*03:05, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA- WSGR Docket No.50401-795.601 B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, (ii) the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA- C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA- C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, and (iii) the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA- DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA- A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA- A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. [0103] In some embodiments, the subject does not express an HLA allele that recognizes each RAS epitope sequence of the multiepitopic polypeptide. [0104] In some embodiments, the subject only expresses HLA alleles that recognize a subset of RAS epitope sequences of the multiepitopic polypeptide. [0105] In some embodiments, the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0106] In some embodiments, the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0107] In some embodiments, the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0108] In some embodiments, the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 27-29. WSGR Docket No.50401-795.601 [0109] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 27, operably linked to a sequence of SEQ ID NO: 29, and operably linked to a sequence of SEQ ID NO: 28. [0110] In some embodiments, the sequence of SEQ ID NO: 27 is operably linked to the sequence of SEQ ID NOs: 29 via a linker, and the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker. [0111] In some embodiments, the linker is a cleavable linker. [0112] In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. [0113] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NOs: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. [0114] In some embodiments, the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker. [0115] In some embodiments, the linker is a cleavable linker. [0116] In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. [0117] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 28, operably linked to a sequence of SEQ ID NO: 27, and operably linked to a sequence of SEQ ID NO: 29. [0118] In some embodiments, the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 is operably linked to a sequence of SEQ ID NO: 29 via a linker. [0119] In some embodiments, the linker is a cleavable linker. [0120] In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. [0121] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 27, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 29. [0122] In some embodiments, the sequence of SEQ ID NO: 27 is operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 is operably linked to a sequence of SEQ ID NO: 29 via a linker. [0123] In some embodiments, the linker is a cleavable linker. [0124] In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. [0125] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 28, operably linked to a sequence of SEQ ID NO: 29, and operably linked to a sequence of SEQ ID NO: 27. WSGR Docket No.50401-795.601 [0126] In some embodiments, the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 29 via a linker, and the sequence of SEQ ID NO: 29 is operably linked to a sequence of SEQ ID NO: 27 via a linker. [0127] In some embodiments, the linker is a cleavable linker. [0128] In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. [0129] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 27, and operably linked to a sequence of SEQ ID NO: 28. [0130] In some embodiments, the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 is operably linked to a sequence of SEQ ID NO: 28 via a linker. [0131] In some embodiments, the linker is a cleavable linker. [0132] In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. [0133] In some embodiments, the RAS polypeptide comprises at least two copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. [0134] In some embodiments, the RAS polypeptide comprises three copies of the multiepitopic polypeptide. [0135] In some embodiments, the RAS polypeptide comprises five copies of the multiepitopic polypeptide. [0136] In some embodiments, the RAS polypeptide further comprises a secretory domain (Sec) sequence at the N terminus of the multiepitopic polypeptide. [0137] In some embodiments, the Sec sequence comprises a sequence of SEQ ID NO: 32. [0138] In some embodiments, the Sec sequence is operably linked to the multiepitopic polypeptide via a linker. [0139] In some embodiments, the linker comprises a sequence of SEQ ID NO: 30 or 112. [0140] In some embodiments, the RAS polypeptide further comprises an MHC class I trafficking domain (MITD) sequence at the C terminus of the multiepitopic polypeptide. [0141] In some embodiments, the MITD sequence comprises a sequence of SEQ ID NO: 33. [0142] In some embodiments, the multiepitopic polypeptide is operably linked to the MITD sequence via a linker. [0143] In some embodiments, the linker comprises a sequence of SEQ ID NO: 30 or 112. WSGR Docket No.50401-795.601 [0144] In some embodiments, the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 25. [0145] In some embodiments, the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 26. [0146] In some embodiments, the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 113. [0147] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. [0148] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14- 23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. [0149] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. [0150] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. [0151] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 14- 16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109. [0152] In some embodiments, the sequence selected from the group consisting of SEQ ID NOs: 14- 16, 84, 92, 96, 100, 104, and 108 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence. [0153] In some embodiments, the linker sequence encodes a cleavable linker. [0154] In some embodiments, the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13. [0155] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20- 23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of WSGR Docket No.50401-795.601 SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. [0156] In some embodiments, the sequence selected from the group consisting of SEQ ID NOs: 20- 23, 88, 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 via a linker sequence. [0157] In some embodiments, the linker sequence encodes a cleavable linker. [0158] In some embodiments, the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13. [0159] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110. [0160] In some embodiments, the sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 is operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 via a linker sequence. [0161] In some embodiments, the linker sequence is a cleavable linker. [0162] In some embodiments, the linker sequence comprises a sequence of selected from the group consisting of SEQ ID NOs: 5, 6, 8-13. [0163] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises at least two copies of a string of sequences, and wherein each string of sequences comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. [0164] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of the string of sequences. [0165] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of the string of sequences. WSGR Docket No.50401-795.601 [0166] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a secretory (Sec) sequence at the 5’end of the string of sequences. [0167] In some embodiments, the sequence encoding the Sec sequence comprises a sequence of SEQ ID NO: 3. [0168] In some embodiments, the sequence encoding the Sec sequence is operably linked to the string of sequences via a linker sequence. [0169] In some embodiments, the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. [0170] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MITD sequence at the 3’ end of the string of sequences. [0171] In some embodiments, the sequence encoding the MITD domain comprises a sequence of SEQ ID NO: 24 or 90. [0172] In some embodiments, the string of sequences is operably linked to the sequence encoding the MITD sequence via a linker sequence. [0173] In some embodiments, the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. [0174] In some embodiments, the recombinant nucleic acid is codon-optimized. [0175] In some embodiments, the recombinant nucleic acid is an RNA. [0176] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 91, 95, 99, 103, 107, 111. [0177] In some embodiments, the subject expresses more of the RAS epitope when administered with the codon-optimized recombinant nucleic acid than administered with wild-type recombinant nucleic acid. [0178] In some embodiments, the TCR comprises a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR beta chain construct comprises a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO: 57. [0179] In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence with at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 52 or SEQ ID NO: 53. [0180] In some embodiments, the TCR beta chain construct comprises a complementarity determining region 1 (CDR1) having an amino acid sequence set forth in SEQ ID NO: 55 and a complementarity determining region 2 (CDR2) having an amino acid sequence set forth in SEQ ID NO: 56. WSGR Docket No.50401-795.601 [0181] In some embodiments, the TCR alpha chain construct comprises a CDR1, a CDR2, and a CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 46, the CDR2 has an amino acid sequence set forth in SEQ ID NO: 47, and the CDR3 has an amino acid sequence set forth in SEQ ID NO: 48. [0182] In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44. [0183] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NO: 49 or SEQ ID NO: 51, or an amino acid sequence that is at least 80% identical to SEQ ID NO: 49 or SEQ ID NO: 51, and (b) an alpha chain having an amino acid sequence set forth in SEQ ID NO: 40 or SEQ ID NO: 42, or an amino acid sequence that is at least 80% identical to SEQ ID NO: 40 or SEQ ID NO: 42. [0184] In some embodiments, the TCR is selected from the TCRs presented in Tables 8A-8D. [0185] In some embodiments, binding of the TCR to the peptide:MHC complex results in production of a cytokine by the immune cell. [0186] In some embodiments, the cytokine is IFN-γ, TNF-α, IL-2, IL-18, or any combination thereof. [0187] Also provided herein is a recombinant nucleic acid encoding a RAS polypeptide comprising a multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length RAS polypeptide and comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, wherein the first RAS epitope sequence and the second RAS epitope sequence are different, and wherein the first RAS amino acid sequence and the second RAS amino acid sequence are linked via a linker. [0188] In some embodiments, presentation of the first and/or second RAS epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide is higher than the presentation of the first and/or second RAS epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. [0189] In some embodiments, the first RAS amino acid sequence is the first epitope sequence and/or the second RAS amino acid sequence is the second epitope sequence. [0190] In some embodiments, the first RAS amino acid sequence consists of the first epitope sequence, and/or the second RAS amino acid sequence consists of the second epitope sequence. [0191] In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation, and/or the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation. WSGR Docket No.50401-795.601 [0192] In some embodiments, the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C. [0193] In some embodiments, the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C. [0194] In some embodiments, the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell. [0195] In some embodiments, the first RAS mutation is G12V, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72. [0196] In some embodiments, the first RAS mutation is G12D, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79. [0197] In some embodiments, the first RAS mutation is G12C, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096. [0198] In some embodiments, the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length RAS polypeptide. [0199] In some embodiments, the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length RAS polypeptide. [0200] In some embodiments, the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker. [0201] In some embodiments, the first RAS amino acid sequence comprises the first RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first RAS epitope sequence from the full-length RAS polypeptide. [0202] In some embodiments, the second RAS amino acid sequence comprises the second RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide. [0203] In some embodiments, the multiepitopic polypeptide does not comprise more than 12 or more consecutive amino acids from the full-length RAS polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length RAS polypeptide. [0204] In some embodiments, the RAS polypeptide further comprises a Secretory (Sec) sequence at the N terminus of the multiepitopic polypeptide. [0205] In some embodiments, the Sec sequence comprises a sequence of SEQ ID NO: 32. [0206] In some embodiments, the Sec sequence is operably linked to the multiepitopic polypeptide via a linker. [0207] In some embodiments, the linker comprises a sequence of SEQ ID NO: 30 or 112. [0208] In some embodiments, the RAS polypeptide further comprises an MHC class I trafficking signal (MITD) sequence at the C terminus of the multiepitopic polypeptide. WSGR Docket No.50401-795.601 [0209] In some embodiments, the MITD sequence comprises a sequence of SEQ ID NO: 33. [0210] In some embodiments, the multiepitopic polypeptide is operably linked to the MITD sequence via a linker. [0211] In some embodiments, the linker comprises a sequence of SEQ ID NO: 30 or 112. [0212] In some embodiments, the multiepitopic polypeptide comprises at least 3, 4, 5, or more different RAS epitope sequences. [0213] In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence are presentable by different HLA alleles, are presented by different HLA alleles, bind to different HLA alleles, are predicted to bind to different HLA alleles, or are predicted to be presented by different HLA alleles. [0214] In some embodiments, the first RAS epitope sequence (i) binds to or is predicted to bind to a first HLA allele with a KD of less than 100 nM and (ii) to binds to or is predicted to bind to a second HLA allele with a KD of more than 500 nM. [0215] In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. [0216] In some embodiments, the multiepitopic polypeptide comprises a first amino acid sequence comprising a first RAS epitope sequence, operably linked to a second amino acid sequence comprising a second RAS epitope sequence, operably linked to a third amino acid sequence comprising a third RAS epitope sequence. [0217] In some embodiments, (i) the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA- B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA- A*03:05, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA- B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, (ii) the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, WSGR Docket No.50401-795.601 HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA- C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02,binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA- C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, and (iii) the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA- DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA- A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA- A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. [0218] In some embodiments, the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2])x-CT seq, where x is an integer from 1 to 10. [0219] In some embodiments, the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2]-cleavable linker2-[Antigen3])x-CT seq, where x is an integer from 1 to 10. [0220] In some embodiments, the NT seq comprises a Secretory (Sec) sequence and a N-terminal linker sequence. [0221] In some embodiments, the CT seq comprises a C-terminal linker and a MITD sequence. [0222] In some embodiments, the Antigen1, Antigen2, or Antigen3 is comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 27-29. [0223] In some embodiments, the cleavable linker1 or cleavable linker2 is selected from the group consisting of SEQ ID NOs: 30 and 31. [0224] In some embodiments, the N-terminal linker sequence or the C-terminal linker sequence is selected from the group consisting of SEQ ID NOs: 30 and 31. WSGR Docket No.50401-795.601 [0225] In some embodiments, the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0226] In some embodiments, the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0227] In some embodiments, the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0228] In some embodiments, the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 27-29. [0229] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 27, operably linked to a sequence of SEQ ID NO: 29, and operably linked to a sequence of SEQ ID NO: 28. [0230] In some embodiments, the sequence of SEQ ID NO: 27 is operably linked to the sequence of SEQ ID NO: 29 via a linker, and the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker. [0231] In some embodiments, the linker is a cleavable linker. [0232] In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. [0233] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. [0234] In some embodiments, the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker. [0235] In some embodiments, the linker is a cleavable linker. [0236] In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. [0237] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 28, operably linked to a sequence of SEQ ID NO: 27, and operably linked to a sequence of SEQ ID NO: 29. [0238] In some embodiments, the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 is operably linked to a sequence of SEQ ID NO: 29 via a linker. [0239] In some embodiments, the linker is a cleavable linker. [0240] In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. [0241] In some embodiments, the RAS polypeptide comprises at least two copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID WSGR Docket No.50401-795.601 NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. [0242] In some embodiments, the RAS polypeptide comprises three copies of the multiepitopic polypeptide. [0243] In some embodiments, the RAS polypeptide comprises five copies of the multiepitopic polypeptide. [0244] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. [0245] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NO:s 14- 23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. [0246] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. [0247] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. [0248] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 14- 16, 84, 92, 96, 100, 104, and 108 , operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109. [0249] In some embodiments, the sequence selected from the group consisting of SEQ ID NOs: 14- 16, 84, 92, 96, 100, 104, and 108 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence. [0250] In some embodiments, the linker sequence encodes a cleavable linker. [0251] In some embodiments, the linker sequence comprises a sequence of selected from the group consisting of SEQ ID NOs: 5, 6, 8-13. [0252] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20- 23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of WSGR Docket No.50401-795.601 SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. [0253] In some embodiments, the sequence selected from the group consisting of SEQ ID NOs: 20- 23, 88, 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 via a linker sequence. [0254] In some embodiments, the linker sequence encodes a cleavable linker. [0255] In some embodiments, the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13. [0256] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110. [0257] In some embodiments, the sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 is operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 via a linker sequence. [0258] In some embodiments, the linker sequence is a cleavable linker. [0259] In some embodiments, the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13. [0260] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises at least two copies of a string of sequences, and wherein each string of sequences comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. [0261] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of the string of sequences. [0262] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of the string of sequences. WSGR Docket No.50401-795.601 [0263] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a Sec sequence at the 5’ end of the string of sequences. [0264] In some embodiments, the sequence encoding the Sec sequence comprises a sequence of SEQ ID NO: 3. [0265] In some embodiments, the sequence encoding the Sec sequence is operably linked to the string of sequences via a linker sequence. [0266] In some embodiments, the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. [0267] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MITD sequence at the 3’ end of the string of sequences. [0268] In some embodiments, the sequence encoding the MITD sequence comprises a sequence of SEQ ID NO: 24 or 90. [0269] In some embodiments, the string of sequences is operably linked to the sequence encoding the MITD sequence via a linker sequence. [0270] In some embodiments, the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. [0271] Also provided herein is a recombinant nucleic acid having at least 60% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 91, 95, 99, 103, 107, 111. [0272] Also provided herein is a recombinant nucleic acid having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 91, 95, 99, 103, 107, 111. [0273] Also provided herein is a polypeptide encoded by the recombinant nucleic acid of any one of the preceding embodiments. [0274] Also provided herein is a pharmaceutical composition comprising the recombinant nucleic acid of any one of the preceding embodiments or the polypeptide of any one of the preceding embodiments, and a pharmaceutically acceptable carrier. [0275] Also provided herein is the recombinant nucleic acid of any one of the preceding embodiments, polypeptide of any one of the preceding embodiments, or the pharmaceutical composition of any one of the preceding embodiments for use in therapy. [0276] Also provided herein is use of the recombinant nucleic acid of any one of the preceding embodiments, the polypeptide of any one of the preceding embodiments, or the pharmaceutical composition of any one of the preceding embodiments, in the manufacture of a medicament for the treatment of cancer in a subject in need thereof. INCORPORATION BY REFERENCE WSGR Docket No.50401-795.601 [0277] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS [0278] The novel features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings of which: [0279] FIGs.1-2 depict an exemplary vaccine construct containing three different antigenic KRAS protein mutants. FIG.1 is a cartoon depicting the protein domains and linkers encoded by the construct. FIG.2 shows the fully annotated sequence of the exemplary construct. [0280] FIGs.3A-3D depict results from a T cell activation experiment measuring IFN-γ secretion by T cells incubated with monocyte-derived dendritic cells (moDCs) transfected with the construct shown in FIG.1, a construct containing three repeats of the antigenic KRAS mutants, an irrelevant construct, or with no moDCs. FIG.3A depicts results using T cells expressing a TCR recognizing KRAS G12V mutant presented by HLA-DRB1:07:01, left and right panels are from different T cell donors. FIG.3B depicts results using T cells expressing a TCR recognizing KRAS G12V mutant presented by HLA-A11:01, left and right panels are from different T cell donors. FIG.3C depicts results using T cells expressing a TCR recognizing KRAS G12D mutant presented by HLA-A11:01, left and right panels are from different T cell donors. FIG.3D depicts results using T cells expressing a TCR recognizing KRAS G12D mutant presented by HLA-C08:02, left and right panels are from different T cell donors. [0281] FIG.4 depicts results from a T cell activation experiment measuring IFN-γ secretion by T cells incubated with monocyte-derived dendritic cells (moDCs) transfected with the constructs described in Table 6. Left and right panels depict results obtained using two different T cell donors. DETAILED DESCRIPTION Definitions [0282] To facilitate an understanding of the present disclosure, a number of terms and phrases are defined below. [0283] An antigen is a foreign substance to the body that induces an immune response. A “neoantigen” refers to a class of tumor antigens which arise from tumor-specific changes in proteins. Neoantigens encompass, but are not limited to, tumor antigens which arise from, for example, a WSGR Docket No.50401-795.601 substitution in a protein sequence, a frame shift mutation, a fusion polypeptide, an in-frame deletion, an insertion, and expression of an endogenous retroviral polypeptide. [0284] A “neoepitope” refers to an epitope that is not present in a reference, such as a non-diseased cell, e.g., a non-cancerous cell or a germline cell, but is found in a diseased cell, e.g., a cancer cell. This includes situations where a corresponding epitope is found in a normal non-diseased cell or a germline cell but, due to one or more mutations in a diseased cell, e.g., a cancer cell, the sequence of the epitope is changed so as to result in the neoepitope. [0285] A “mutation” refers to a change of or a difference in a nucleic acid sequence (e.g., a nucleotide substitution, addition or deletion) compared to a reference nucleic acid. A “somatic mutation” can occur in any of the cells of the body except the germ cells (sperm and egg) and are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. In some embodiments, a mutation is a non-synonymous mutation. A “non-synonymous mutation” refers to a mutation, for (e.g., a nucleotide substitution), which does result in an amino acid change such as an amino acid substitution in the translation product. A “frameshift” occurs when a mutation disrupts the normal phase of a gene’s codon periodicity (also known as “reading frame”), resulting in translation of a non-native protein sequence. It is possible for different mutations in a gene to achieve the same altered reading frame. [0286] “Antigen processing” or “processing” refers to the degradation of a polypeptide or antigen into procession products, which are fragments of said polypeptide or antigen (e.g., the degradation of a polypeptide into peptides) and the association of one or more of these fragments (e.g., via binding) with MHC molecules for presentation by cells, for example, antigen presenting cells, to specific T cells. [0287] An “antigen presenting cell” (APC) refers to a cell which presents peptide fragments of protein antigens in association with MHC molecules on its cell surface. The term includes professional antigen presenting cells (e.g., B lymphocytes, monocytes, dendritic cells, Langerhans cells) as well as other antigen presenting cells (e.g., keratinocytes, endothelial cells, astrocytes, fibroblasts, oligodendrocytes). In some cases, the APC can be a cancer cell. [0288] The term “affinity” refers to a measure of the strength of binding between two members of a binding pair (e.g., a human leukocyte antigen (HLA)-binding peptide and a class I or II HLA, or a peptide-HLA complex and a T cell receptor (TCR)). KD refers to the dissociation constant between two members of a binding pair and has units of molarity. KA refers to the affinity constant between two members of a binding pair is the inverse of the dissociation constant. Affinity may be determined experimentally, for example by surface plasmon resonance (SPR) using commercially available Biacore SPR units. Koff refers to the off-rate constant of two members of a binding pair, (e.g., the off- rate constant of an HLA-binding peptide and a class I or II HLA, or a peptide-HLA complex and a WSGR Docket No.50401-795.601 TCR). Kon refers to the on-rate constant of two members of a binding pair, (e.g., the on-rate constant of an HLA-binding peptide and a class I or II HLA, or a peptide-HLA complex and a TCR). [0289] Throughout this disclosure, “binding data” results may be expressed in terms of an “IC50.” Affinity may also be expressed as the inhibitory concentration 50 (IC50), or the concentration at which 50% of a first member of a binding pair (e.g., a peptide) is displaced. Likewise, ln(IC50) refers to the natural log of the IC50. For example, an IC50 may be the concentration of a tested peptide in a binding assay at which 50% inhibition of binding of a labeled reference peptide is observed. Given the conditions in which the assays are run (e.g., limiting HLA protein concentrations and/or labeled reference peptide concentrations), these values can approximate KD values. Assays for determining binding are well known in the art and are described in detail, for example, in PCT publications WO 94/20127 and WO 94/03205, and other publications such Sidney et al., Current Protocols in Immunology 18.3.1 (1998); Sidney, et al., J. Immunol.154:247 (1995); and Sette, et al., Mol. Immunol.31:813 (1994). Alternatively, binding can be expressed relative to binding by a reference standard peptide. Binding can also be determined using other assay systems including those using: live cells (e.g., Ceppellini et al., Nature 339:392 (1989); Christnick et al., Nature 352:67 (1991); Busch et al., Int. Immunol.2:443 (1990); Hill et al., J. Immunol.147:189 (1991); del Guercio et al., J. Immunol.154:685 (1995)), cell free systems using detergent lysates (e.g., Cerundolo et al., J. Immunol.21:2069 (1991)), immobilized purified MHC (e.g., Hill et al., J. Immunol.152, 2890 (1994); Marshall et al., J. Immunol.152:4946 (1994)), ELISA systems (e.g., Reay et al., EMBO J. 11:2829 (1992)), surface plasmon resonance (e.g., Khilko et al., J. Biol. Chem.268:15425 (1993)); high flux soluble phase assays (Hammer et al., J. Exp. Med.180:2353 (1994)), and measurement of class I MHC stabilization or assembly (e.g., Ljunggren et al., Nature 346:476 (1990); Schumacher et al., Cell 62:563 (1990); Townsend et al., Cell 62:285 (1990); Parker et al., J. Immunol.149:1896 (1992)). [0290] The term “derived” when used to discuss an epitope is a synonym for “prepared.” A derived epitope can be isolated from a natural source, or it can be synthesized according to standard protocols in the art. Synthetic epitopes can comprise artificial amino acid residues “amino acid mimetics,” such as D isomers of natural occurring L amino acid residues or non-natural amino acid residues such as cyclohexylalanine. A derived or prepared epitope can be an analog of a native epitope. The term “derived from” refers to the origin or source, and may include naturally occurring, recombinant, unpurified, purified or differentiated molecules or cells. For example, an expanded or induced antigen specific T cell may be derived from a T cell. For example, an expanded or induced antigen specific T cell may be derived from an antigen specific T cell in a biological sample. For example, a matured APC (e.g., a professional APC) may be derived from a non-matured APC (e.g., an immature APC). For example, an APC may be derived from a monocyte (e.g., a CD14+ monocyte). For example, a WSGR Docket No.50401-795.601 dendritic cell may be derived from a monocyte (e.g., a CD14+ monocyte). For example, an APC may be derived from a bone marrow cell. [0291] An “epitope” is the collective features of a molecule (e.g., a peptide’s charge and primary, secondary and tertiary structure) that together form a site recognized by another molecule (e.g., an immunoglobulin, T cell receptor, HLA molecule, or chimeric antigen receptor). For example, an epitope can be a set of amino acid residues involved in recognition by a particular immunoglobulin; a Major Histocompatibility Complex (MHC) receptor; or in the context of T cells, those residues recognized by a T cell receptor protein and/or a chimeric antigen receptor. Epitopes can be prepared by isolation from a natural source, or they can be synthesized according to standard protocols in the art. Synthetic epitopes can comprise artificial amino acid residues, amino acid mimetics, (such as D isomers of naturally-occurring L amino acid residues or non-naturally-occurring amino acid residues). Throughout this disclosure, epitopes may be referred to in some cases as peptides or peptide epitopes. In certain embodiments, there is a limitation on the length of a peptide of the present disclosure. The embodiment that is length-limited occurs when the protein or peptide comprising an epitope described herein comprises a region (i.e., a contiguous series of amino acid residues) having 100% sequence identity with a native sequence. In order to avoid the definition of epitope from reading, e.g., on whole natural molecules, there is a limitation on the length of any region that has 100% sequence identity with a native peptide sequence. Thus, for a peptide comprising an epitope described herein and a region with 100% sequence identity with a native peptide sequence, the region with 100% sequence identity to a native sequence generally has a length of: less than or equal to 600 amino acid residues, less than or equal to 500 amino acid residues, less than or equal to 400 amino acid residues, less than or equal to 250 amino acid residues, less than or equal to 100 amino acid residues, less than or equal to 85 amino acid residues, less than or equal to 75 amino acid residues, less than or equal to 65 amino acid residues, and less than or equal to 50 amino acid residues. In certain embodiments, an “epitope” described herein is comprised by a peptide having a region with less than 51 amino acid residues that has 100% sequence identity to a native peptide sequence, in any increment down to 5 amino acid residues; for example 50, 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residues. [0292] A “T cell epitope” refers to a peptide sequence bound by an MHC molecule in the form of a peptide-MHC (pMHC) complex. A peptide-MHC complex can be recognized and bound by a TCR of a T cell (e.g., a cytotoxic T-lymphocyte or a T-helper cell). [0293] A “T cell” includes CD4+ T cells and CD8+ T cells. The term T cell also includes both T helper 1 type T cells and T helper 2 type T cells. T cells may be generated by the method described in the application, for a clinical application. T cells or adoptive T cells referred to here, such as for a WSGR Docket No.50401-795.601 clinical application are cells isolated from a biological source, manipulated and cultured ex vivo and prepared into a drug candidate for a specific therapy such as a cancer, e.g., melanoma. When drug candidate cells pass specific qualitative and quantitative criteria for fitness for a clinical application, the drug candidate may be designated a drug product. In some cases, a drug product is selected from a number of drug candidates. In the context of this application, a drug product is a T cell, more specifically, a population of T cells, or more specifically a population of T cells with heterogeneous characteristics and subtypes. For example, a drug product, as disclosed herein may have a population of T cells comprising CD8+ T cells, CD4+ T cells, with cells at least above a certain exhibiting antigen specificity, a certain percentage of each exhibiting a memory phenotype, among others. [0294] An “immune cell” refers to a cell that plays a role in the immune response. Immune cells are of hematopoietic origin, and include lymphocytes, such as B cells and T cells; natural killer cells; myeloid cells, such as monocytes, macrophages, eosinophils, mast cells, basophils, and granulocytes. [0295] An “immunogenic” peptide or an “immunogenic” epitope or an “immunogenic” peptide epitope is a peptide that binds to an HLA molecule and induces a cell-mediated or humoral response, for example, a cytotoxic T lymphocyte (CTL) response, a helper T lymphocyte (HTL) response and/or a B lymphocyte response. Immunogenic peptides described herein are capable of binding to an HLA molecule and thereafter induce a cell-mediated or humoral response (e.g., a CTL (cytotoxic) response, or a HTL response) to the peptide. [0296] A “protective immune response” or “therapeutic immune response” refers to a CTL and/or an HTL response to an antigen derived from a pathogenic antigen (e.g., a tumor antigen), which in some way prevents or at least partially arrests disease symptoms, side effects or progression. The immune response can also include an antibody response which has been facilitated by the stimulation of helper T cells. [0297] A “T cell receptor” (“TCR”) refers to a molecule, whether natural or partly or wholly synthetically produced, found on the surface of T lymphocytes (T cells) that recognizes an antigen bound to a major histocompatibility complex (MHC) molecule. The ability of a T cells to recognize an antigen associated with various diseases (e.g., cancers) or infectious organisms is conferred by its TCR, which is made up of both an alpha (α) chain and a beta (β) chain or a gamma (γ) and a delta (δ) chain. The proteins which make up these chains are encoded by DNA, which employs a unique mechanism for generating the tremendous diversity of the TCR. This multi-subunit immune recognition receptor associates with the CD3 complex and binds peptides presented by the MHC class I and II proteins on the surface of antigen-presenting cells (APCs). Binding of a TCR to a peptide on an APC is a central event in T cell activation. [0298] As used herein, a “chimeric antigen receptor” or “CAR” refers to an antigen binding protein in that includes an immunoglobulin antigen binding domain (e.g., an immunoglobulin variable WSGR Docket No.50401-795.601 domain) and a T cell receptor (TCR) constant domain. As used herein, a “constant domain” of a TCR polypeptide includes a membrane-proximal TCR constant domain, a TCR transmembrane domain and/or a TCR cytoplasmic domain, or fragments thereof. For example, in some embodiments, a CAR is a monomer that includes a polypeptide comprising an immunoglobulin heavy chain variable domain linked to a TCRβ constant domain. In some embodiments, the CAR is a dimer that includes a first polypeptide comprising an immunoglobulin heavy or light chain variable domain linked to a TCRα or TCRβconstant domain and a second polypeptide comprising an immunoglobulin heavy or light chain variable domain (e.g., a κ or λ variable domain) linked to a TCRβ or TCRα constant domain. [0299] “Major Histocompatibility Complex” or “MHC” is a cluster of genes that plays a role in control of the cellular interactions responsible for physiologic immune responses. The terms “major histocompatibility complex” and the abbreviation “MHC” can include any class of MHC molecule, such as MHC class I and MHC class II molecules, and relate to a complex of genes which occurs in all vertebrates. In humans, the MHC complex is also known as the human leukocyte antigen (HLA) complex. Thus, a “Human Leukocyte Antigen” or “HLA” refers to a human Major Histocompatibility Complex (MHC) protein (see, e.g., Stites, et al., Immunology, 8TH Ed., Lange Publishing, Los Altos, Calif. (1994). For a detailed description of the MHC and HLA complexes, see, Paul, Fundamental Immunology, 3rd Ed., Raven Press, New York (1993). [0300] The major histocompatibility complex in the genome comprises the genetic region whose gene products expressed on the cell surface are important for binding and presenting endogenous and/or foreign antigens and thus for regulating immunological processes. MHC proteins or molecules are important for signaling between lymphocytes and antigen presenting cells or diseased cells in immune reactions. MHC proteins or molecules bind peptides and present them for recognition by T- cell receptors. The proteins encoded by the MHC can be expressed on the surface of cells, and display both self-antigens (peptide fragments from the cell itself) and non-self-antigens (e.g., fragments of invading microorganisms) to a T-cell. MHC binding peptides can result from the proteolytic cleavage of protein antigens and represent potential lymphocyte epitopes. (e.g., T cell epitope and B cell epitope). MHCs can transport the peptides to the cell surface and present them there to specific cells, such as cytotoxic T-lymphocytes, T-helper cells, or B cells. The MHC region can be divided into three subgroups, class I, class II, and class III. MHC class I proteins can contain an α-chain and β2- microglobulin (not part of the MHC encoded by chromosome 15). They can present antigen fragments to cytotoxic T-cells. MHC class II proteins can contain α- and β-chains and they can present antigen fragments to T-helper cells. MHC class III region can encode for other immune components, such as complement components and cytokines. The MHC can be both polygenic (there are several MHC class I and MHC class II genes) and polymorphic (there are multiple alleles of each gene). WSGR Docket No.50401-795.601 [0301] A “receptor” refers to a biological molecule or a molecule grouping capable of binding a ligand. A receptor may serve, to transmit information in a cell, a cell formation or an organism. A receptor comprises at least one receptor unit, for example, where each receptor unit may consist of a protein molecule. A receptor has a structure which complements that of a ligand and may complex the ligand as a binding partner. The information is transmitted in particular by conformational changes of the receptor following complexation of the ligand on the surface of a cell. In some embodiments, a receptor is to be understood as meaning in particular proteins of MHC classes I and II capable of forming a receptor/ligand complex with a ligand, in particular a peptide or peptide fragment of suitable length. A “ligand” refers to a molecule which has a structure complementary to that of a receptor and is capable of forming a complex with this receptor. In some embodiments, a ligand is to be understood as meaning a peptide or peptide fragment which has a suitable length and suitable binding motifs in its amino acid sequence, so that the peptide or peptide fragment is capable of forming a complex with MHC proteins such as MHC class I or MHC class II proteins. In some embodiments, a “receptor/ligand complex” is also to be understood as meaning a “receptor/peptide complex” or “receptor/peptide fragment complex”, including a peptide- or peptide fragment- presenting MHC molecule such as MHC class I or MHC class II molecules. [0302] A “native” or a “wild type” sequence refers to a sequence found in nature. The term “naturally occurring” as used herein refers to the fact that an object can be found in nature. For example, a peptide or nucleic acid that is present in an organism (including viruses) and can be isolated from a source in nature and which has not been intentionally modified by man in the laboratory is naturally occurring. [0303] The terms “peptide” and “peptide epitope” are used interchangeably with “oligopeptide” in the present specification to designate a series of residues connected one to the other, typically by peptide bonds between the α-amino and carboxyl groups of adjacent amino acid residues. A “synthetic peptide” refers to a peptide that is obtained from a non-natural source, e.g., is man-made. Such peptides can be produced using such methods as chemical synthesis or recombinant DNA technology. “Synthetic peptides” include “fusion proteins.” [0304] The term “motif” refers to a pattern of residues in an amino acid sequence of defined length, for example, a peptide of less than about 15 amino acid residues in length, or less than about 13 amino acid residues in length, for example, from about 8 to about 13 amino acid residues (e.g., 8, 9, 10, 11, 12, or 13) for a class I HLA motif and from about 6 to about 25 amino acid residues (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25) for a class II HLA motif, which is recognized by a particular HLA molecule. Motifs are typically different for each HLA protein encoded by a given human HLA allele. These motifs differ in their pattern of the primary and secondary anchor residues. In some embodiments, an MHC class I motif identifies a peptide of 7, 89, WSGR Docket No.50401-795.601 10, 11, 12 or 13 amino acid residues in length. In some embodiments, an MHC class II motif identifies a peptide of 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 amino acid residues in length. A “cross-reactive binding” peptide refers to a peptide that binds to more than one member of a class of a binding pair members (e.g., a peptide bound by both a class I HLA molecule and a class II HLA molecule). [0305] The term “residue” refers to an amino acid residue or amino acid mimetic residue incorporated into a peptide or protein by an amide bond or amide bond mimetic, or that is encoded by a nucleic acid (DNA or RNA). The nomenclature used to describe peptides or proteins follows the conventional practice. The amino group is presented to the left (the amino- or N-terminus) and the carboxyl group to the right (the carboxy- or C-terminus) of each amino acid residue. When amino acid residue positions are referred to in a peptide epitope, they are numbered in an amino to carboxyl direction with the first position being the residue located at the amino terminal end of the epitope, or the peptide or protein of which it can be a part. In the formulae representing selected specific embodiments of the present disclosure, the amino- and carboxyl-terminal groups, although not specifically shown, are in the form they can assume at physiologic pH values, unless otherwise specified. In the amino acid structure formulae, each residue is generally represented by standard three letter or single letter designations. The L-form of an amino acid residue is represented by a capital single letter or a capital first letter of a three-letter symbol, and the D-form for those amino acid residues having D-forms is represented by a lower case single letter or a lower case three letter symbol. However, when three letter symbols or full names are used without capitals, they can refer to L amino acid residues. Glycine has no asymmetric carbon atom and is simply referred to as “Gly” or “G”. The amino acid sequences of peptides set forth herein are generally designated using the standard single letter symbol. (A, Alanine; C, Cysteine; D, Aspartic Acid; E, Glutamic Acid; F, Phenylalanine; G, Glycine; H, Histidine; I, Isoleucine; K, Lysine; L, Leucine; M, Methionine; N, Asparagine; P, Proline; Q, Glutamine; R, Arginine; S, Serine; T, Threonine; V, Valine; W, Tryptophan; and Y, Tyrosine.) [0306] A “conservative amino acid substitution” is one in which one amino acid residue is replaced with another amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). For example, substitution of a phenylalanine for a tyrosine is a conservative WSGR Docket No.50401-795.601 substitution. Methods of identifying nucleotide and amino acid conservative substitutions which do not eliminate peptide function are well-known in the art. [0307] “Pharmaceutically acceptable” refers to a generally non-toxic, inert, and/or physiologically compatible composition or component of a composition. A “pharmaceutical excipient” or “excipient” comprises a material such as an adjuvant, a carrier, pH-adjusting and buffering agents, tonicity adjusting agents, wetting agents, preservatives, and the like. A “pharmaceutical excipient” is an excipient which is pharmaceutically acceptable. [0308] According to the present disclosure, the term “vaccine” relates to a pharmaceutical preparation (pharmaceutical composition) or product that upon administration induces an immune response, for example, a cellular or humoral immune response, which recognizes and attacks a pathogen or a diseased cell such as a cancer cell. A vaccine may be used for the prevention or treatment of a disease. The term “individualized cancer vaccine” or “personalized cancer vaccine” “personal cancer vaccine” concerns a particular cancer patient and means that a cancer vaccine is adapted to the needs or special circumstances of an individual cancer patient. [0309] The terms “polynucleotide” and “nucleic acid” are used interchangeably herein and refer to polymers of nucleotides of any length, and include DNA and RNA, for example, mRNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and/or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase. In some embodiments, the polynucleotide and nucleic acid can be in vitro transcribed mRNA. In some embodiments, the polynucleotide that is administered using the methods of the present disclosure is mRNA. [0310] The terms “isolated” or “biologically pure” refer to material which is substantially or essentially free from components which normally accompany the material as it is found in its native state. Thus, isolated peptides described herein do not contain some or all of the materials normally associated with the peptides in their in situ environment. For example, an “isolated” epitope can be an epitope that does not include the whole sequence of the protein from which the epitope was derived. For example, a naturally-occurring polynucleotide or peptide present in a living animal is not isolated, but the same polynucleotide or peptide, separated from some or all of the coexisting materials in the natural system, is isolated. Such a polynucleotide could be part of a vector, and/or such a polynucleotide or peptide could be part of a composition, and still be “isolated” in that such vector or composition is not part of its natural environment. Isolated RNA molecules include in vivo or in vitro RNA transcripts of the DNA molecules described herein, and further include such molecules produced synthetically. In some embodiments, a polypeptide, antibody, polynucleotide, vector, cell, or composition which is isolated is substantially pure. The term “substantially pure” as used herein WSGR Docket No.50401-795.601 refers to material which is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure. [0311] The terms “identical” or percent “identity” in the context of two or more nucleic acids or polypeptides, refer to two or more sequences or subsequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned (introducing gaps, if necessary) for maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity. The percent identity can be measured using sequence comparison software or algorithms or by visual inspection. Various algorithms and software that can be used to obtain alignments of amino acid or nucleotide sequences are well-known in the art. These include, but are not limited to, BLAST, ALIGN, Megalign, BestFit, GCG Wisconsin Package, and variations thereof. In some embodiments, two nucleic acids or polypeptides described herein are substantially identical, meaning they have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, and in some embodiments at least 95%, 96%, 97%, 98%, 99% nucleotide or amino acid residue identity, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection. In some embodiments, identity exists over a region of the sequences that is at least about 10, at least about 20, at least about 40-60 residues, at least about 60-80 residues in length or any integral value there between. In some embodiments, identity exists over a longer region than 60-80 residues, such as at least about 80-100 residues, and in some embodiments the sequences are substantially identical over the full length of the sequences being compared, such as an amino acid sequence of a peptide or a coding region of a nucleotide sequence. [0312] The term “subject” refers to any animal (e.g., a mammal), including, but not limited to, humans, non-human primates, canines, felines, rodents, and the like, which is to be the recipient of a particular treatment. Typically, the terms “subject” and “patient” are used interchangeably herein in reference to a human subject. [0313] The terms “effective amount” or “therapeutically effective amount” or “therapeutic effect” refer to an amount of a therapeutic effective to “treat” a disease or disorder in a subject or mammal. The therapeutically effective amount of a drug has a therapeutic effect and as such can prevent the development of a disease or disorder; slow down the development of a disease or disorder; slow down the progression of a disease or disorder; relieve to some extent one or more of the symptoms associated with a disease or disorder; reduce morbidity and mortality; improve quality of life; or a combination of such effects. [0314] The terms “treating” or “treatment” or “to treat” or “alleviating” or “to alleviate” refer to both (1) therapeutic measures that cure, slow down, lessen symptoms of, and/or halt progression of a diagnosed pathologic condition or disorder and (2) prophylactic or preventative measures that prevent WSGR Docket No.50401-795.601 or slow the development of a targeted pathologic condition or disorder. Thus, those in need of treatment include those already with the disorder; those prone to have the disorder; and those in whom the disorder is to be prevented. [0315] The term “depleted” when used to describe a cell sample (e.g., a peripheral blood mononuclear cell (PBMC) sample) refers to a cell sample in which a subpopulation of cells has been removed or depleted. For example, an immune cell sample depleted of CD25 expressing cells refers to an immune cell sample in which CD25 expressing cells have been removed or depleted. For example, one or more binding agents can be used to remove or deplete one or more cells or cell types from a sample. For example, CD14+ cells can be depleted or removed from a PBMC sample, such as by using an antibody that binds to CD14. [0316] The “stimulation” refers to a response induced by binding of a stimulatory molecule with its cognate ligand thereby mediating a signal transduction event. For example, stimulation of a T cell can refer to binding of a TCR of a T cell to a peptide-MHC complex. For example, stimulation of a T cell can refer to a step within protocol 1 or protocol 2 in which PBMCs are cultured together with peptide loaded APCs. [0317] The term “enriched” refers to a composition or fraction wherein an object species has been partially purified such that the concentration of the object species is substantially higher than the naturally occurring level of the species in a finished product without enrichment. The term “induced cell” refers to a cell that has been treated with an inducing compound, cell, or population of cells that affects the cell’s protein expression, gene expression, differentiation status, shape, morphology, viability, and the like. [0318] A “reference” can be used to correlate and/or compare the results obtained in the methods of the present disclosure from a diseased specimen. Typically, a “reference” may be obtained on the basis of one or more normal specimens, in particular specimens which are not affected by a disease, either obtained from an individual or one or more different individuals (e.g., healthy individuals), such as individuals of the same species. A “reference” can be determined empirically by testing a sufficiently large number of normal specimens. [0319] As used herein, a tumor unless otherwise mentioned, is a cancerous tumor, and the terms cancer and tumor are used interchangeably throughout the document. While a tumor is a cancer of solid tissue, several of the compositions and methods described herein are in principle applicable to cancers of the blood, leukemia. Overview [0320] After infusion of T cells (e.g., ex vivo activated T cells, or T-cell receptor engineered T cells (TCR-T cells)) into a patient with cancer, the cells can circulate until they encounter their cognate epitope, typically on a tumor cell. In the case of solid tumors, this can be challenging because the T WSGR Docket No.50401-795.601 cells can infiltrate the tumor and survive the harsh tumor microenvironment. Partly due to this challenge, infused T cell numbers and frequency may decline relatively rapidly after infusion. Additionally, the dose of infused TCR-T cells may be important in clinical response across several studies. [0321] One strategy to support the engraftment, expansion and persistence of infused T cells after infusion can include administering a vaccine that encodes the target antigen. In this case, however, the vaccine design can differ and may be a determinant of the success of this approach. The vaccine may encode for the full-length protein to be presented on the surface of cells. The vaccine strings designed to lead to optimal cleavage of the target epitopes can lead to more (e.g., 10-100 times more) of the desired epitope being presented on major histocompatibility complex (MHC) molecules encoded by HLA alleles than when the full-length RAS protein is used. The full-length RAS polypeptide can be a full-length KRAS, NRAS or HRAS polypeptide. This method can enable the vaccine to induce robust display of the target epitope in a patient and subsequent stimulation of transferred T cells, whereas the dose attainable with the full-length RAS protein may be insufficient in some cases. [0322] The vaccine may encode targets epitopes presented by MHC molecules encoded by HLA- A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA- C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-DRB1*11:01, HLA-A*03:02, HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, and HLA-A*03:05. Provided herein are vaccine constructs to present at least the target epitope on each of these HLA alleles. There are multiple considerations, including the order of the epitopes, the number of times each epitope is encoded, the codon optimization approach, and the mRNA format. A series of in vitro and in vivo assays have been defined to prioritize and select the best vaccine design, starting by choosing the best codon optimization approach and then selecting the best order of the epitopes. This information can be used to evaluate the approach in vivo. For example, a mouse model for this approach can utilize mice expressing human HLA and MHC. HLA-engineered tumor cells can also be utilized to evaluate the approach. RAS Vaccines [0323] The present disclosure provides RAS vaccines comprising RAS polypeptides or recombinant nucleic acids encoding RAS polypeptides that, when expressed, can result in presentation of one or more epitopes of RAS by one or more MHC molecules encoded by one or more HLA alleles. [0324] Provided herein is a recombinant nucleic acid encoding a RAS polypeptide comprising a multiepitopic polypeptide. In some embodiments, the RAS polypeptide does not comprise a full- length RAS polypeptide. In some embodiments, the RAS polypeptide comprises a first RAS amino acid sequence comprising a first RAS epitope sequence. In some embodiments, the RAS polypeptide comprises a second RAS amino acid sequence comprising a second RAS epitope sequence. In some WSGR Docket No.50401-795.601 embodiments, the first RAS epitope sequence and the second RAS epitope sequence are different. In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence are linked via a linker. In some embodiments, presentation of the first and/or second RAS epitope sequence as a peptide:MHC complex by the antigen presenting cells (APCs) of the subject administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide is higher than the presentation of the first and/or second RAS epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. In some embodiments, the first RAS amino acid sequence is the first epitope sequence. In some embodiments, the second RAS amino acid sequence is the second epitope sequence. In some embodiments, the first RAS amino acid sequence is the first epitope sequence and the second RAS amino acid sequence is the second epitope sequence. In some embodiments, the first RAS amino acid sequence consists of the first epitope sequence. In some embodiments, the second RAS amino acid sequence consists of the second epitope sequence. In some embodiments, the first RAS amino acid sequence consists of the first epitope sequence and the second RAS amino acid sequence consists of the second epitope sequence. In some cases, each different RAS epitope sequence is separated by a linker. [0325] In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation. In some embodiments, the second RAS amino acid sequence comprises a second RAS mutation. In some embodiments, the second RAS mutation is different from the first RAS mutation. In some embodiments, the second RAS mutation is same as the first RAS mutation. In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation, and the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation. In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation, and the second RAS amino acid sequence comprises a second RAS mutation same as the first RAS mutation. [0326] In some embodiments, the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C. In some embodiments, the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C. [0327] In some embodiments, the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell. In some embodiments, the first RAS mutation is G12V, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72. In some embodiments, the first RAS mutation is G12D, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79. In some embodiments, the first RAS mutation is G12C, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096. In some embodiments, the first RAS epitope sequence first RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to WSGR Docket No.50401-795.601 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide. In some embodiments, the second RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide. [0328] In some embodiments, the first RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide. In some embodiments, the second RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide. [0329] In some embodiments, the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker. In some embodiments, the first RAS amino acid sequence comprises the first RAS epitope sequence and one, two, three, four, five or more residues flanking the N-terminus or C-terminus of the first RAS epitope sequence from the full length RAS polypeptide. In some embodiments, the second RAS amino acid sequence comprises the second RAS epitope sequence and one, two, three, four, five or more residues flanking the N-terminus or C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide. [0330] In some embodiments the multiepitopic polypeptide does not comprise more than 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more consecutive amino acids from the full-length RAS polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise more than 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more consecutive amino acids from the full-length RAS polypeptide. [0331] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a secretory (Sec) sequence. In some embodiments, the Sec sequence is at the N terminus of the multiepitopic polypeptide. In some embodiments the Sec sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80% , at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 32. In some embodiments the Sec sequence comprises a sequence of SEQ ID NO: 32. In some embodiments, the Sec sequence is operably linked to the multiepitopic polypeptide via a linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 30. In some embodiments, the linker comprises a sequence of SEQ ID NO: 30. In some embodiments, the Sec sequence is operably linked to the multiepitopic polypeptide via a linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence having at least 60%, at least WSGR Docket No.50401-795.601 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 30. In some cases, the linker comprises a sequence of SEQ ID NO: 31. [0332] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MHC I Trafficking Domain (MITD) sequence. In some embodiments, the sequence encoding an MITD sequence is at the C terminus of the multiepitopic polypeptide. In some embodiments, the MITD sequence comprises at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 33. In some embodiments, the MITD sequence comprises a sequence of SEQ ID NO: 33. In some embodiments, the multiepitopic polypeptide is operably linked to the MITD domain. In some embodiments, the multiepitopic polypeptide is operably linked to the MITD domain via a linker sequence. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 30. In some embodiments, the linker comprises a sequence of SEQ ID NO: 30. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0333] In some embodiments, the multiepitopic polypeptide comprises a RAS polypeptide. In some embodiments, the sequence of the multiepitopic polypeptide is the same RAS epitope sequence. In some embodiments, the sequence of the multiepitopic polypeptide is a different RAS epitope sequence. In some embodiments, the multiepitopic polypeptide comprises at least 2 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 3 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 4 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 5 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 6 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 8 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 9 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 10 or more different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide is a RAS polypeptide comprising the first RAS epitope sequence and the second RAS epitope sequence. [0334] In some embodiments, the multiepitopic polypeptide comprises a first RAS epitope sequence, operably linked to a second RAS epitope sequence. In some embodiments, the first RAS epitope WSGR Docket No.50401-795.601 sequence and the second RAS epitope sequence are the same. In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence are different. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are presentable by different HLA alleles. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are presented by different HLA alleles. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are predicted to bind to different HLA alleles. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are predicted to be presented by different HLA alleles. [0335] In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 500nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 400nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 300nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele. In some embodiments, a first RAS epitope sequence is predicted to bind to a first HLA allele. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 200nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 100nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 50nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 1nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele. In some embodiments, a first RAS epitope sequence is predicted to bind to a second HLA allele. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 200nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 300nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 500nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 600nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 700nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 800nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 900nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 1000nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 1nM and binds to second HLA allele with a KD of more than 200nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 50nM and binds to second HLA allele with a KD of more than 300nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 100nM and binds to second HLA allele with a KD of more than 500nM. In some embodiments, a first WSGR Docket No.50401-795.601 RAS epitope sequence binds to a first HLA allele with a KD of less than 200 nM and binds to second HLA allele with a KD of more than 600 nM. [0336] In some embodiments, the linker comprises at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0337] In some embodiments, the multiepitopic polypeptide comprises a first RAS epitope sequence, operably linked to a second RAS epitope sequence, operably linked to a third RAS epitope sequence. [0338] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*11:01 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*11:01 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*11:01 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*11:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*11:01 allele. [0339] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*03:01 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*03:01 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*03:01 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*03:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*03:01 allele. [0340] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*30:01 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*30:01 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*30:01 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*30:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*30:01 allele. WSGR Docket No.50401-795.601 [0341] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*68:01 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*68:01 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*68:01 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*68:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*68:01 allele. [0342] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-B allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-B*40:01 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-B*40:01 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- B*40:01 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-B*40:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-B*40:01 allele. [0343] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*01:02 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*01:02 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*01:02 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*01:02 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*01:02 allele. [0344] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*03:03 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*03:03 allele. [0345] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the first RAS epitope WSGR Docket No.50401-795.601 sequence is presented by an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*03:04 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*03:04 allele. [0346] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-DRB1 allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-DRB1*07:01 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-DRB1*07:01 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA-DRB1*07:01 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-DRB1*07:01 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA- DRB1*07:01 allele. [0347] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*03:02 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*03:02 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*03:02 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*03:02 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*03:02 allele. [0348] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*03:05 allele. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*03:05 allele. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*03:05 allele. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*03:05 allele. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*03:05 allele. [0349] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-B allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-B*07:02 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-B*07:02 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA- WSGR Docket No.50401-795.601 B*07:02 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-B*07:02 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-B*07:02 allele. [0350] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*03:04 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*03:04 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*03:04 allele. [0351] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*05:01 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*05:01 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*05:01 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*05:01 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*05:01 allele. [0352] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*-3:01 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*-3:01 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA-A*- 3:01 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*-3:01 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*-3:01 allele. [0353] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*-11:01 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*-11:01 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA-A*- 11:01 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*-11:01 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*-11:01 allele. WSGR Docket No.50401-795.601 [0354] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*-68:01 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*-68:01 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA-A*- 68:01 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*-68:01 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*-68:01 allele. [0355] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele. In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*08:02 allele. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*08:02 allele. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*08:02 allele. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*08:02 allele. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*08:02 allele. [0356] In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-DRB allele. In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-DRB1*11:01 allele. In some embodiments, the third RAS epitope sequence is presented by an MHC molecule encoded by an HLA-DRB1*11:01 allele. In some embodiments, the third RAS epitope sequence binds to an MHC molecule encoded by an HLA-DRB1*11:01 allele. In some embodiments, the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-DRB1*11:01 allele. In some embodiments, the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA- DRB1*11:01 allele. [0357] In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*3:01 allele. In some embodiments, the third RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*3:01 allele. In some embodiments, the third RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*3:01 allele. In some embodiments, the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*3:01 allele. In some embodiments, the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*3:01 allele. [0358] In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the third RAS epitope sequence is presentable by WSGR Docket No.50401-795.601 an MHC molecule encoded by an HLA-A*11:01 allele. In some embodiments, the third RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*11:01 allele. In some embodiments, the third RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*11:01 allele. In some embodiments, the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*11:01 allele. In some embodiments, the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*11:01 allele. [0359] In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A allele. In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-A*68:01 allele. In some embodiments, the third RAS epitope sequence is presented by an MHC molecule encoded by an HLA-A*68:01 allele. In some embodiments, the third RAS epitope sequence binds to an MHC molecule encoded by an HLA- A*68:01 allele. In some embodiments, the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-A*68:01 allele. In some embodiments, the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-A*68:01 allele. [0360] In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C allele. In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the third RAS epitope sequence is presented by an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the third RAS epitope sequence binds to an MHC molecule encoded by an HLA- C*03:03 allele. In some embodiments, the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA-C*03:03 allele. In some embodiments, the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA-C*03:03 allele. [0361] In some embodiments, the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2])x-CT seq, where x is an integer from 1 to 50. In some embodiments, the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2])x-CT seq, where x is an integer from 1 to 25. In some embodiments, the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1- [Antigen2])x-CT seq, where x is an integer from 1 to 10. [0362] In some embodiments, the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2]-cleavable linker2-[Antigen3])x-CT seq, where x is an integer from 1 to 50. In some embodiments, the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2]-cleavable linker2-[Antigen3])x-CT seq, where x is an integer from 1 to 25. In some cases, the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2]-cleavable linker2-[Antigen3])x-CT seq, where x is an integer from 1 to 10. WSGR Docket No.50401-795.601 [0363] In some embodiments, the NT seq comprises a secretory (Sec) sequence and a N-terminal linker sequence. In some embodiments, the CT seq comprises a C-terminal linker and a MITD sequence. In some embodiments, the Antigen1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the Antigen2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the Antigen3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 27- 29. In some cases, the cleavable linker1 or cleavable linker2 comprise a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to any one of SEQ ID NOs: 30 or 31. In some embodiments, the cleavable linker1 or cleavable linker2 is selected from the group consisting of SEQ ID NOs: 30 and 31. In some embodiments, the N-terminal linker sequence is selected from the group consisting of SEQ ID NOs: 30 and 31. In some embodiments, the C-terminal linker sequence is selected from the group consisting of SEQ ID NOs: 30 and 31. [0364] In some embodiments, the RAS polypeptide comprises a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises a sequence with at least 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises a sequence with at least 90% sequence identity to SEQ ID NO: 75. In some embodiments, the RAS polypeptide comprises a sequence of SEQ ID NO: 27. [0365] In some embodiments, the RAS polypeptide comprises a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises a sequence with at least 80% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises a sequence of SEQ ID NO: 28. [0366] In some embodiments, the RAS polypeptide comprises a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises a sequence of SEQ ID NO: 29. [0367] In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least WSGR Docket No.50401-795.601 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 27. [0368] In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 80% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 28. [0369] In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 29. [0370] In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 27. [0371] In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 80% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 28. [0372] In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 80% sequence identity to SEQ WSGR Docket No.50401-795.601 ID NO: 29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 29. [0373] In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 27. [0374] In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 80% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 28. [0375] In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 29. [0376] In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 27. [0377] In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 80% sequence WSGR Docket No.50401-795.601 identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 28. [0378] In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 29. [0379] In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 27. [0380] In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 80% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 28. [0381] In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 29. [0382] In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least WSGR Docket No.50401-795.601 80% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence of SEQ ID NO: 27. [0383] In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 80% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence of SEQ ID NO: 28. [0384] In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 60% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 70% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 80% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 90% sequence identity to SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence of SEQ ID NO: 29. [0385] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28. [0386] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 via a linker. In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, WSGR Docket No.50401-795.601 the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 29 via a linker, and the sequence of SEQ ID NO: 29 operably linked to the sequence of SEQ ID NO: 28 via a linker. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0387] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27. [0388] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 via a linker. In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 operably linked to the sequence of SEQ ID NO: 27 via a linker. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some WSGR Docket No.50401-795.601 embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0389] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 29. [0390] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 via a linker. In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 operably linked to the sequence of SEQ ID NO: 29 via a linker. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. WSGR Docket No.50401-795.601 [0391] In some embodiments, the RAS polypeptide comprises two copies of a multiepitopic polypeptide. In some embodiments each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27. [0392] In some embodiments, the RAS polypeptide comprises three copies of a multiepitopic polypeptide. In some embodiments each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27. [0393] In some embodiments, the RAS polypeptide comprises four copies of a multiepitopic polypeptide. In some embodiments each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27. [0394] In some embodiments, the RAS polypeptide comprises five copies of a multiepitopic polypeptide. In some embodiments each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27. [0395] In some embodiments, the RAS polypeptide comprises six copies of a multiepitopic polypeptide. In some embodiments each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27. [0396] In some embodiments, the RAS polypeptide comprises seven copies of a multiepitopic polypeptide. In some embodiments each copy of the multiepitopic polypeptide comprises, from N to C terminus, a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 28, operably linked to a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 27. [0397] Also provided herein are recombinant nucleic acids encoding multiepitopic polypeptides. [0398] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. WSGR Docket No.50401-795.601 [0399] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 14. [0400] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 15. [0401] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID WSGR Docket No.50401-795.601 NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 16. [0402] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 17. [0403] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 18. [0404] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS WSGR Docket No.50401-795.601 polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 19. [0405] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 20. [0406] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 21. [0407] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a WSGR Docket No.50401-795.601 sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 22. [0408] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 23. [0409] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 84. [0410] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic WSGR Docket No.50401-795.601 acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 86. [0411] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 88. [0412] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 92. [0413] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% WSGR Docket No.50401-795.601 sequence identity to a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 93. [0414] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 94. [0415] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 96. [0416] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 97. In some embodiments, the WSGR Docket No.50401-795.601 recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 97. [0417] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 98. [0418] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 100. [0419] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence WSGR Docket No.50401-795.601 having at least 60% sequence identity to a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 101. [0420] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 102. [0421] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 104. [0422] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 105. In some WSGR Docket No.50401-795.601 embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 105. [0423] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 106. [0424] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 108. [0425] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at WSGR Docket No.50401-795.601 least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 109. [0426] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 110. [0427] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100- 102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a WSGR Docket No.50401-795.601 sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, WSGR Docket No.50401-795.601 at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS WSGR Docket No.50401-795.601 polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 110. [0428] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences with at least 90% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104- 106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ WSGR Docket No.50401-795.601 ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 110. [0429] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14- 23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID WSGR Docket No.50401-795.601 NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 105. In some embodiments, WSGR Docket No.50401-795.601 the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 110. [0430] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide WSGR Docket No.50401-795.601 comprises two copies of a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 110. [0431] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 88. WSGR Docket No.50401-795.601 In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 110. [0432] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid WSGR Docket No.50401-795.601 encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 110. [0433] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a WSGR Docket No.50401-795.601 sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 108. In some embodiments, the recombinant WSGR Docket No.50401-795.601 nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 110. [0434] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 23. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 93. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 94. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 96. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 98. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 100. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 101. WSGR Docket No.50401-795.601 In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 102. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 104. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 106. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 110. [0435] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109. [0436] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109. [0437] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence selected from the group consisting of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109. [0438] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected WSGR Docket No.50401-795.601 from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 operably linked to a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity the sequence selected from the group consisting of SEQ ID NO: 17- 19, 86, 93, 97, 101, 105, and 109 via a linker sequence. [0439] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 90% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence having at least 90% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence identity the sequence selected from the group consisting of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence. [0440] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 operably linked to a sequence selected from the group consisting of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence. [0441] In some embodiments, the linker sequence encodes a cleavable linker. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence WSGR Docket No.50401-795.601 identity to a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 13. [0442] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 80% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence having at least 80% sequence identity the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence having at least 80% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108. [0443] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108. [0444] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: WSGR Docket No.50401-795.601 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108. [0445] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence. [0446] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence. [0447] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence selected from the group consisting of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence. [0448] In some embodiments, the linker sequence encodes a cleavable linker. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or WSGR Docket No.50401-795.601 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 13. [0449] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at WSGR Docket No.50401-795.601 least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110. [0450] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110. [0451] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence selected from the group consisting of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110. [0452] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence and the sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence. [0453] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-19, via a linker sequence and the sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence. WSGR Docket No.50401-795.601 [0454] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence and the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence selected from the group consisting of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence. [0455] In some embodiments, the linker sequence encodes a cleavable linker. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 13. WSGR Docket No.50401-795.601 [0456] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises at least two copies of a string of sequences. In some embodiments, each string of sequences comprises, 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. In some embodiments, each string of sequences comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 90% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. In some embodiments, each string of sequences comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises seven copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises eight copies of the string of sequences. [0457] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a secretory (Sec) sequence. In some embodiments, the Sec sequence is at the 5’ end of the string of sequences. In some embodiments, the Sec sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 3. In some WSGR Docket No.50401-795.601 embodiments the Sec sequence comprises a sequence of SEQ ID NO: 3. In some embodiments, the sequence encoding the Sec sequence is operably linked to the string of sequences via a linker sequence. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. In some embodiments, the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. [0458] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MHC I Trafficking Domain (MITD) sequence. In some embodiments, the sequence encoding an MITD sequence is at the 3’ end of the string of sequences. In some embodiments the MITD sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 24 or 90. In some embodiments the MITD sequence comprises a sequence of SEQ ID NO: 24 or 90. In some embodiments, the string of sequences is operably linked to the sequence encoding the MITD domain. In some embodiments, the string of sequences is operably linked to the sequence encoding the MITD domain via a linker sequence. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. In some embodiments, the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. [0459] Provided herein is a recombinant nucleic acid comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 95. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, WSGR Docket No.50401-795.601 at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 103. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 111. [0460] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 95. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 103. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 111. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 95. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 103. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 111. Immune Cells [0461] The present disclosure provides immune cells (e.g., T cells) expressing a T cell receptor (TCR) or a chimeric antigen receptor. T cell receptors can also comprise endogenous T cell receptors WSGR Docket No.50401-795.601 that have been activated. Immune cells expressing a TCR can be activated and/or expanded using methods such as NEO-STIM. T cell receptors can comprise receptors encoded by recombinant nucleic acids that are specific for a RAS polypeptide or fragment thereof. [0462] Provided herein is a recombinant nucleic acid encoding a TCR. In some embodiments, the TCR comprises a TCR beta chain construct. In some embodiments the TCR comprises a TCR alpha chain construct. In some embodiments, the TCR comprises a TCR beta chain construct and a TCR alpha chain construct. In some embodiments, the TCR binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 5 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 27, 58-62 and 65-72 and a human MHC encoded by an HLA allele selected from the group consisting of HLA- A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA- C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 7 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 27, 58-62 and 65-72 and a human MHC encoded by an HLA allele selected from the group consisting of HLA- A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA- C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 5 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 28, 75-79 and a human MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 7 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 28, 75-79 and a human MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 5 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 29, 81, 82, and 1096 and a human MHC encoded by an HLA allele selected from the group consisting of HLA- DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 7 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 29, 81, 82, and 1096 and a human MHC encoded by an HLA allele selected from the group consisting of HLA- DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. [0463] In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least WSGR Docket No.50401-795.601 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 58. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 59. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 60. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 61. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 62. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 65. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 66. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 67. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 68. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 69. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 70. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 71. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 72. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 75. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence WSGR Docket No.50401-795.601 identity to a sequence of SEQ ID NO: 76. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 77. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 78. In some embodiments the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 79. In some embodiments the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 29. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 81. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 82. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 1096. [0464] In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 58. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 59. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 60. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 61. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 62. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 65. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 66. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 67. In some embodiments, the peptide:MHC complex WSGR Docket No.50401-795.601 comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 68. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 69. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 70. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 71. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 72. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 75. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 76. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 77. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 78. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 79. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 29. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 81. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 82. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 1096. [0465] In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 58. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 59. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 60. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 61. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 62. In some embodiments the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 65. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 66. In some WSGR Docket No.50401-795.601 embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 67. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 68. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 69. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 70. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 71. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 72. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 75. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 76. In some embodiments the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 77. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 78. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 79. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 29. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 81. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 82. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 1096. [0466] Also provided herein is a cell comprising the recombinant nucleic acids presented herein. In some embodiments, the cell is an immune cell. In some embodiments, the cell is a myeloid lineage cell. In some embodiments, the cell is a lymphocyte. In some embodiments, the cell is a B cell. In some embodiments, the cell is a T cell. In some cases, upon binding of the TCR to the peptide:MHC complex, the cell produces a proinflammatory cytokine. In some cases, the proinflammatory cytokine is IFN-γ. In some cases, the proinflammatory cytokine is TNF-α. In some cases, the proinflammatory cytokine is IL-12. In some cases, the proinflammatory cytokine is IL-6. In some cases, the proinflammatory cytokine is IL-17. In some embodiments, the proinflammatory cytokine is a chemokine. In some cases, upon binding of the TCR to the peptide:MHC complex, cell division is increased. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 2% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In WSGR Docket No.50401-795.601 some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 5% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 10% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 15% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 25% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 50% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 100% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 150% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 200% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 500% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. [0467] Also provided herein is a recombinant nucleic acid encoding a TCR comprising a TCR beta chain construct. In some embodiments, the recombinant nucleic acid encoding a TCR comprises a TCR alpha chain construct. In some embodiments, the beta chain construct comprises a complementarity determining region 3 (CDR3). In some embodiments, the beta chain CDR3 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 57. In some embodiments, the beta chain CDR3 comprises an amino acid sequence set forth in SEQ ID NO: 57. In some embodiments, the TCR beta chain construct comprises a variable region comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to identity to an amino acid sequence set forth in SEQ ID NO: 52 or SEQ ID NO: 53. In some embodiments, the TCR beta chain construct comprises a variable region comprising a sequence having at least 80% sequence identity to WSGR Docket No.50401-795.601 an amino acid sequence set forth in SEQ ID NO: 52 or SEQ ID NO: 53. In some embodiments, the TCR beta chain construct comprises a variable region comprising an amino acid sequence set forth in SEQ ID NO: 52 or SEQ ID NO: 53. In some embodiments, the TCR beta chain construct comprises a complementarity determining region 1 (CDR1) having an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 55 and a complementarity determining region 2 (CDR2) having an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 56. In some embodiments, the TCR beta chain construct comprises a complementarity determining region 1 (CDR1) having an amino acid sequence set forth in SEQ ID NO: 55 and a complementarity determining region 2 (CDR2) having an amino acid set forth in SEQ ID NO: 56. In some embodiments, the TCR alpha chain construct comprises a CDR1, a CDR2, and a CDR3. In some embodiments, the CDR1 comprises an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence set forth in SEQ ID NO: 46, the CDR2 comprises an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to identity toa sequence set forth in SEQ ID NO: 47, and the CDR3 comprises an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence set forth in SEQ ID NO: 48. In some embodiments, the CDR1 comprises an amino acid sequence set forth in SEQ ID NO: 46, the CDR2 comprises an amino acid sequence set forth in SEQ ID NO: 47, and the CDR3 comprises an amino acid sequence set forth in SEQ ID NO: 48. In some embodiments, the TCR alpha chain construct comprises a variable region comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to identity to an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44. In some embodiments, the TCR alpha chain construct comprises a variable region comprising a sequence having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44. In some embodiments, the TCR alpha chain construct comprises a variable region comprising an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44. In some embodiments, the TCR comprises a beta chain having an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to SEQ ID NO: 49 or SEQ ID NO: 51 and an alpha chain having an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to SEQ ID NO: 40 or SEQ ID NO: 42. In some embodiments, the TCR comprises a beta chain having an amino acid WSGR Docket No.50401-795.601 sequence that is at least 80% identical to SEQ ID NO: 49 or SEQ ID NO: 51 and an alpha chain having an amino acid sequence that is at least 80% identical to SEQ ID NO: 40 or SEQ ID NO: 42. In some embodiments, the TCR comprises a beta chain having an amino acid sequence set forth in SEQ ID NO: 49 or SEQ ID NO: 51 and an alpha chain having an amino acid sequence set forth in SEQ ID NO: 40 or SEQ ID NO: 42. Methods of Treatment [0468] The methods of the disclosure can be used to treat any type of cancer known in the art. Non- limiting examples of cancers to be treated by the methods of the present disclosure can include melanoma (e.g., metastatic malignant melanoma), renal cancer (e.g., clear cell carcinoma), prostate cancer (e.g., hormone refractory prostate adenocarcinoma), pancreatic adenocarcinoma, breast cancer, colon cancer, lung cancer (e.g., non-small cell lung cancer), cutaneous melanoma, synovial sarcoma, myxoid and round cell liposarcoma, osteosarcoma, and neuroblastoma ,esophageal cancer, squamous cell carcinoma of the head and neck, liver cancer, ovarian cancer, cervical cancer, thyroid cancer, glioblastoma, glioma, leukemia, lymphoma, and other neoplastic malignancies. [0469] Additionally, the disease or condition provided herein includes refractory or recurrent malignancies whose growth may be inhibited using the methods of treatment of the present disclosure. In some embodiments, a cancer to be treated by the methods of treatment of the present disclosure is selected from the group consisting of carcinoma, squamous carcinoma, adenocarcinoma, sarcomata, endometrial cancer, breast cancer, ovarian cancer, cervical cancer, fallopian tube cancer, primary peritoneal cancer, colon cancer, colorectal cancer, squamous cell carcinoma of the anogenital region, melanoma and renal cell carcinoma. [0470] Specific examples of cancers that can be prevented and/or treated in accordance with present disclosure include, but are not limited to, the following: renal cancer, kidney cancer, glioblastoma multiforme, metastatic breast cancer; breast carcinoma; breast sarcoma; neurofibroma; neurofibromatosis; pediatric tumors; neuroblastoma; malignant melanoma; carcinomas of the epidermis; leukemias such as but not limited to, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemias such as myeloblastic, promyelocytic, myelomonocytic, monocytic, erythroleukemia leukemias and myclodysplastic syndrome, chronic leukemias such as but not limited to, chronic myelocytic (granulocytic) leukemia, chronic lymphocytic leukemia, hairy cell leukemia; polycythemia vera; lymphomas such as but not limited to Hodgkin’s disease, non-Hodgkin’s disease; multiple myelomas such as but not limited to smoldering multiple myeloma, nonsecretory myeloma, osteosclerotic myeloma, plasma cell leukemia, solitary plasmacytoma and extramedullary plasmacytoma; Waldenstrom’s macroglobulinemia; monoclonal gammopathy of undetermined significance; benign monoclonal gammopathy; heavy chain disease; bone cancer and connective tissue sarcomas such as but not limited to bone sarcoma, myeloma bone disease, multiple myeloma, WSGR Docket No.50401-795.601 cholesteatoma-induced bone osteosarcoma, Paget’s disease of bone, osteosarcoma, chondrosarcoma, Ewing’s sarcoma, malignant giant cell tumor, fibrosarcoma of bone, chordoma, periosteal sarcoma, soft-tissue sarcomas, angiosarcoma (hemangiosarcoma), fibrosarcoma, Kaposi’s sarcoma, leiomyosarcoma, liposarcoma, lymphangio sarcoma, neurilemmoma, rhabdomyosarcoma, and synovial sarcoma; brain tumors such as but not limited to, glioma, astrocytoma, brain stem glioma, ependymoma, oligodendroglioma, nonglial tumor, acoustic neurinoma, craniopharyngioma, medulloblastoma, meningioma, pineocytoma, pineoblastoma, and primary brain lymphoma; breast cancer including but not limited to adenocarcinoma, lobular (small cell) carcinoma, intraductal carcinoma, medullary breast cancer, mucinous breast cancer, tubular breast cancer, papillary breast cancer, Paget’s disease (including juvenile Paget’s disease) and inflammatory breast cancer; adrenal cancer such as but not limited to pheochromocytoma and adrenocortical carcinoma; thyroid cancer such as but not limited to papillary or follicular thyroid cancer, medullary thyroid cancer and anaplastic thyroid cancer; pancreatic cancer such as but not limited to, insulinoma, gastrinoma, glucagonoma, vipoma, somatostatin-secreting tumor, and carcinoid or islet cell tumor; pituitary cancers such as but limited to Cushing’s disease, prolactin-secreting tumor, acromegaly, and diabetes insipius; eye cancers such as but not limited to ocular melanoma such as iris melanoma, choroidal melanoma, and cilliary body melanoma, and retinoblastoma; vaginal cancers such as squamous cell carcinoma, adenocarcinoma, and melanoma; vulvar cancer such as squamous cell carcinoma, melanoma, adenocarcinoma, basal cell carcinoma, sarcoma, and Paget’s disease; cervical cancers such as but not limited to, squamous cell carcinoma, and adenocarcinoma; uterine cancers such as but not limited to endometrial carcinoma and uterine sarcoma; ovarian cancers such as but not limited to, ovarian epithelial carcinoma, borderline tumor, germ cell tumor, and stromal tumor; cervical carcinoma; esophageal cancers such as but not limited to, squamous cancer, adenocarcinoma, adenoid cystic carcinoma, mucoepidermoid carcinoma, adenosquamous carcinoma, sarcoma, melanoma, plasmacytoma, verrucous carcinoma, and oat cell (small cell) carcinoma; stomach cancers such as but not limited to, adenocarcinoma, fungating (polypoid), ulcerating, superficial spreading, diffusely spreading, malignant lymphoma, liposarcoma, fibrosarcoma, and carcinosarcoma; colon cancers; colorectal cancer, colon carcinoma; rectal cancers; liver cancers such as but not limited to hepatocellular carcinoma and hepatoblastoma, gallbladder cancers such as adenocarcinoma; cholangiocarcinomas such as but not limited to pappillary, nodular, and diffuse; lung cancers such as non-small cell lung cancer, non-small cell lung cancer, squamous cell carcinoma (epidermoid carcinoma), adenocarcinoma, large-cell carcinoma and small-cell lung cancer; lung carcinoma; testicular cancers such as but not limited to germinal tumor, seminoma, anaplastic, classic (typical), spermatocytic, nonseminoma, embryonal carcinoma, teratoma carcinoma, choriocarcinoma (yolk-sac tumor), prostate cancers such as but not limited to, androgen-independent prostate cancer, androgen- WSGR Docket No.50401-795.601 dependent prostate cancer, adenocarcinoma, leiomyosarcoma, and rhabdomyosarcoma; penal cancers; oral cancers such as but not limited to squamous cell carcinoma; basal cancers; salivary gland cancers such as but not limited to adenocarcinoma, mucoepidermoid carcinoma, and adenoidcystic carcinoma; pharynx cancers such as but not limited to squamous cell cancer, and verrucous; skin cancers such as but not limited to, basal cell carcinoma, squamous cell carcinoma and melanoma, superficial spreading melanoma, nodular melanoma, lentigo malignant melanoma, acrallentiginous melanoma; kidney cancers such as but not limited to renal cell cancer, adenocarcinoma, hypernephroma, fibrosarcoma, transitional cell cancer (renal pelvis and/or uterus); renal carcinoma; Wilms’ tumor; bladder cancers such as but not limited to transitional cell carcinoma, squamous cell cancer, adenocarcinoma, carcinosarcoma. In addition, cancers include myxosarcoma, osteogenic sarcoma, endotheliosarcoma, lymphangioendotheliosarcoma, mesothelioma, synovioma, hemangioblastoma, epithelial carcinoma, cystadenocarcinoma, bronchogenic carcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma and papillary adenocarcinomas. Cancers include, but are not limited to, B cell cancer, e.g., multiple myeloma, Waldenstrom’s macroglobulinemia, the heavy chain diseases, such as, for example, alpha chain disease, gamma chain disease, and mu chain disease, benign monoclonal gammopathy, and immunocytic amyloidosis, melanomas, breast cancer, lung cancer, bronchus cancer, colorectal cancer, prostate cancer (e.g., metastatic, hormone refractory prostate cancer), pancreatic cancer, stomach cancer, ovarian cancer, urinary bladder cancer, brain or central nervous system cancer, peripheral nervous system cancer, esophageal cancer, cervical cancer, uterine or endometrial cancer, cancer of the oral cavity or pharynx, liver cancer, kidney cancer, testicular cancer, biliary tract cancer, small bowel or appendix cancer, salivary gland cancer, thyroid gland cancer, adrenal gland cancer, osteosarcoma, chondrosarcoma, cancer of hematological tissues, and the like. Other non-limiting examples of types of cancers applicable to the methods encompassed by the present disclosure include human sarcomas and carcinomas, e.g., fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing’s tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, colorectal cancer, pancreatic cancer, breast cancer, ovarian cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, liver cancer, choriocarcinoma, seminoma, embryonal carcinoma, Wilms’ tumor, cervical cancer, bone cancer, brain tumor, testicular cancer, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma; leukemias, e.g., acute WSGR Docket No.50401-795.601 lymphocytic leukemia and acute myelocytic leukemia (myeloblastic, promyelocytic, myelomonocytic, monocytic and erythroleukemia); chronic leukemia (chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia); and polycythemia vera, lymphoma (Hodgkin’s disease and non- Hodgkin’s disease), multiple myeloma, Waldenstrom’s macroglobulinemia, and heavy chain disease. In some embodiments, the cancer whose phenotype is determined by the method of the present disclosure is an epithelial cancer such as, but not limited to, bladder cancer, breast cancer, cervical cancer, colon cancer, gynecologic cancers, renal cancer, laryngeal cancer, lung cancer, oral cancer, head and neck cancer, ovarian cancer, pancreatic cancer, prostate cancer, or skin cancer. In other embodiments, the cancer is breast cancer, prostate cancer, lung cancer, or colon cancer. In still other embodiments, the epithelial cancer is non-small-cell lung cancer, nonpapillary renal cell carcinoma, cervical carcinoma, ovarian carcinoma (e.g., serous ovarian carcinoma), or breast carcinoma. The epithelial cancers may be characterized in various other ways including, but not limited to, serous, endometrioid, mucinous, clear cell, brenner, or undifferentiated. In some embodiments, the present disclosure is used in the treatment, diagnosis, and/or prognosis of lymphoma or its subtypes, including, but not limited to, mantle cell lymphoma. Lymphoproliferative disorders are also considered to be proliferative diseases. [0471] The present disclosure provides a method of treating a subject with a disease or condition. The disease or condition can comprise a cancer. The method can comprise administering to the subject a therapy comprising a multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide. The multiepitopic polypeptide can comprise a RAS polypeptide. The RAS polypeptide may not be a full-length RAS polypeptide. In some embodiments, each sequence of the multiepitopic polypeptide can be a different RAS epitope sequence. In some embodiments, the antigen presenting cells (APCs) of the subject administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide can present a RAS epitope sequence as a peptide:MHC complex. In some embodiments, the APCs of the subject present more of a RAS epitope sequence compared to the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. In some embodiments, the APCs of the subject express more peptide:MHC complexes comprising the RAS epitope sequence compared to the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. In some embodiments, the APCs of the subject express more of the RAS epitope sequence compared to the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. In some embodiments, the full-length RAS polypeptide is a full-length KRAS, NRAS or HRAS polypeptide. [0472] In some embodiments, the therapy comprises a cell comprising the multiepitopic polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the WSGR Docket No.50401-795.601 multiepitopic polypeptide comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence. In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence are different. In some embodiments, the presentation of the first and/or second RAS epitope sequence as a peptide:MHC complex by APCs of the subject administered the therapy is higher than the presentation of the first and/or second RAS epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. In some embodiments, the full-length RAS polypeptide is a full-length KRAS, NRAS or HRAS polypeptide. In some embodiments, the first RAS amino acid sequence is a first KRAS, NRAS or HRAS amino acid sequence. In some embodiments, the second RAS amino acid sequence is a second KRAS, NRAS or HRAS amino acid sequence. [0473] In some cases, the APCs of the subject administered with the multiepitopic polypeptide having different RAS epitopes can present more (e.g., at least 1.1 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 5.5 times, 6 times, 6.5 times, 7 times, 7.5 times, 8 times, 8.5 times, 9 times, 9.5 times, 10 times, 20 times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times, 100 times, 120 times, 150 times, 200 times or more) of a RAS epitope sequence compared to the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. Presentation can be measured by mass spectrometry detecting RAS -specific MHC molecules following lysis and protein extraction of APCs. Presentation can also be measured by mass spectrometry detecting components of the RAS epitope sequence. [0474] In some cases, the APCs having (e.g., transfected or otherwise delivered with) the multiepitopic polypeptide having different RAS epitopes can present more (e.g., at least 1.1 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 5.5 times, 6 times, 6.5 times, 7 times, 7.5 times, 8 times, 8.5 times, 9 times, 9.5 times, 10 times, 20 times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times, 100 times, 120 times, 150 times, 200 times or more) of a RAS epitope sequence compared to the APCs having the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. Presentation can be measured by mass spectrometry detecting RAS -specific MHC molecules following lysis and protein extraction of APCs. Presentation can also be measured by mass spectrometry detecting components of the RAS epitope sequence. [0475] In some embodiments, the method further comprises administering to the subject a T-cell receptor (TCR) or a cell comprising the TCR. In some embodiments, the method comprises administering to the subject a recombinant nucleic acid encoding the TCR or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR. In some embodiments, the method further WSGR Docket No.50401-795.601 comprises administering to the subject a cell comprising a chimeric antigen receptor (CAR) or a recombinant nucleic acid encoding the CAR. [0476] The multiepitopic polypeptide comprising a RAS polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide administered in the subject can elicit specific T cell responses of the T cells expressing TCRs that can recognize RAS epitopes in complex with MHC molecules. [0477] When administered in the subject, the multiepitopic polypeptide having different RAS epitopes can elicit enhanced T cell responses compared to the full-length RAS polypeptide. For example, the multiepitopic polypeptide comprising a RAS polypeptide comprising a different RAS epitopes (or the recombinant nucleic acid encoding the RAS polypeptide) administered in a subject can lead to increased cytokine release by the RAS specific T cells of at least 1.1 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 5.5 times, 6 times, 6.5 times, 7 times, 7.5 times, 8 times, 8.5 times, 9 times, 9.5 times, 10 times, 20 times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times, or 100 times more compared to that in a subject administered with the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. For another example, APCs having (e.g., transfected or otherwise delivered with) the multiepitopic polypeptide comprising a RAS polypeptide comprising different RAS epitopes (or the recombinant nucleic acid encoding the RAS polypeptide) can lead to increased cytokine release by the RAS specific T cells of at least 1.1 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 5.5 times, 6 times, 6.5 times, 7 times, 7.5 times, 8 times, 8.5 times, 9 times, 9.5 times, 10 times, 20 times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times, or 100 times more compared to APCs having the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. Cytokine release can be measured using a cytometric bead assay, ELISA, or any other suitable method of quantifying levels of cytokine release. [0478] In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence is separated by a linker. In some cases, the first RAS amino acid sequence is the first epitope sequence. In some cases, the second RAS amino acid sequence is the second epitope sequence. In some cases, the first RAS amino acid sequence is the first epitope sequence and the second RAS amino acid sequence is the second epitope sequence. In some embodiments, the first RAS amino acid sequence consists of the first epitope sequence. In some embodiments, the second the second RAS amino acid sequence consists of the second epitope sequence. In some embodiments, the first RAS amino acid sequence consists of the first epitope sequence and the second the second RAS amino acid sequence consists of the second epitope sequence. [0479] In some embodiments, each different RAS epitope sequence is separated by a linker. [0480] In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation. In some embodiments, the second RAS amino acid sequence comprises a second RAS mutation. In some WSGR Docket No.50401-795.601 embodiments, the second RAS mutation is different from the first RAS mutation. In some embodiments, the second RAS mutation is same as the first RAS mutation. In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation, and the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation. In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation, and the second RAS amino acid sequence comprises a second RAS mutation same as the first RAS mutation. [0481] In some embodiments, the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C. In some embodiments, the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C. [0482] In some embodiments, the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell. In some embodiments, the first RAS mutation is G12V, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72. In some embodiments, the first RAS mutation is G12D, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79. In some embodiments, the first RAS mutation is G12C, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096. In some embodiments, the first RAS epitope sequence first RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide. In some embodiments, the second RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide. [0483] In some embodiments, the first RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide. In some embodiments, the second RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide. [0484] In some embodiments, the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker. In some embodiments, the first RAS amino acid sequence comprises the first RAS epitope sequence and one, two, three, four, five or more residues flanking the N-terminus or C-terminus of the first RAS epitope sequence from the full length RAS polypeptide. In some embodiments, the second RAS amino acid sequence comprises the second RAS epitope sequence and one, two, three, four, five or more residues flanking the N-terminus or C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide. [0485] In some embodiments the multiepitopic polypeptide does not comprise more than 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more consecutive amino acids from the full-length RAS polypeptide. WSGR Docket No.50401-795.601 In some embodiments, the multiepitopic polypeptide does not comprise more than 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more consecutive amino acids from the full-length RAS polypeptide. [0486] In some embodiments, the TCR recognizes and binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises the first RAS epitope sequence and a human MHC encoded by an HLA allele. In some embodiments, the TCR recognizes and binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises the second RAS epitope sequence and a human MHC encoded by an HLA allele. [0487] Also provided herein is a method of treating a subject with a disease or condition. In some embodiments, the disease or condition can comprise cancer. In some embodiments, the method comprises administering to the subject a RAS polypeptide. In some embodiments, the method comprises administering to the subject a recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the method comprises administering to the subject a cell comprising the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the RAS polypeptide comprises a RAS epitope sequence. In some embodiments, the subject has been previously administered a T-cell receptor (TCR). In some embodiments, the subject has been previously administered a recombinant nucleic acid encoding the TCR or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR. In some embodiments, the TCR recognizes and binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence. In some embodiments, the peptide:MHC complex comprises a human MHC encoded by an HLA allele. In some embodiments, the peptide:MHC complex comprises (i) the RAS epitope sequence and (ii) a human MHC encoded by an HLA allele. [0488] Also provided herein is a method of treating a subject with a disease or condition. In some embodiments, the disease or condition can comprise a cancer. In some embodiments, the method comprises administering to the subject a T-cell receptor (TCR). In some embodiments, the method comprises administering to the subject a recombinant nucleic acid encoding the TCR. In some embodiments, the method can comprise administering to the subject an immune cell comprising the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the TCR recognizes and binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence. In some embodiments, the peptide:MHC complex comprises a human MHC encoded by an HLA allele. In some embodiments, the peptide:MHC complex comprises (i) a RAS epitope sequence and (ii) a human MHC encoded by an HLA allele. In some embodiments, the subject has been previously administered a RAS polypeptide. In some embodiments, the subject has been previously administered a recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the RAS polypeptide comprises the RAS epitope sequence. WSGR Docket No.50401-795.601 [0489] Also provided herein is a method of treating a subject with a disease or condition. In some embodiments, the disease or condition can comprise a cancer. In some embodiments, the method comprises administering to the subject a RAS polypeptide. In some embodiments, the method comprises administering to the subject a recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the RAS polypeptide comprises a RAS epitope sequence. In some embodiments, the method comprises administering the subject a TCR or an immune cell comprising the TCR. In some embodiments, the method comprises administering to the subject a recombinant nucleic acid encoding the TCR or an immune cell comprising the TCR or the recombinant nucleic acid encoding the TCR. In some embodiments, the TCR recognizes and binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence. In some embodiments, the peptide:MHC complex comprises a human MHC encoded by an HLA allele. In some embodiments, the peptide:MHC complex comprises (i) a RAS epitope sequence and (ii) a human MHC encoded by an HLA allele. In some embodiments, the method comprises administering to the subject the RAS polypeptide concurrently with the TCR or an immune cell comprising the TCR. In some embodiments, the method comprises administering to the subject the RAS polypeptide concurrently with the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the method comprises administering to the subject the recombinant nucleic acid encoding the RAS polypeptide concurrently with the TCR or an immune cell comprising the TCR. In some embodiments, the method comprises administering to the subject the recombinant nucleic acid encoding the RAS polypeptide concurrently with the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the method comprises administering to the subject the RAS polypeptide prior to the TCR or an immune cell comprising the TCR. In some embodiments, the method comprises administering to the subject the RAS polypeptide prior to the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the method comprises administering to the subject the recombinant nucleic acid encoding the RAS polypeptide prior to the TCR or an immune cell comprising the TCR. In some embodiments, the method comprises administering to the subject the recombinant nucleic acid encoding the RAS polypeptide prior to the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the method comprises administering to the subject the RAS polypeptide subsequent to the TCR or an immune cell comprising the TCR. In some embodiments, the method comprises administering to the subject the RAS polypeptide subsequent to the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the method comprises administering to the subject the recombinant WSGR Docket No.50401-795.601 nucleic acid encoding the RAS polypeptide subsequent to the TCR or an immune cell comprising the TCR. In some embodiments, the method comprises administering to the subject the recombinant nucleic acid encoding the RAS polypeptide subsequent to the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. The TCR described herein can be a soluble TCR. The TCR described herein can be a membrane-bound TCR. The TCR described herein can be expressed by an immune cell. [0490] In some embodiments, the method comprises administering a cell comprising the RAS polypeptide or nucleic acid encoding the RAS polypeptide concurrently with administering to the subject a TCR, a recombinant nucleic acid encoding the TCR or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS peptide sequence, and (ii) a human MHC encoded by an HLA allele. In some embodiments, the method comprises administering a cell comprising the RAS polypeptide or nucleic acid encoding the RAS polypeptide subsequent to administering to the subject a TCR, a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS peptide sequence, and (ii) a human MHC encoded by an HLA allele. In some embodiments, the method comprises administering a cell comprising the RAS polypeptide or nucleic acid encoding the RAS polypeptide prior to administering to the subject a TCR, a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS peptide sequence, and (ii) a human MHC encoded by an HLA allele. [0491] The RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more after the subject has been administered the TCR or the recombinant nucleic acid encoding the TCR. The RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more after the subject has been administered an immune cell comprising the TCR or the recombinant nucleic acid encoding the TCR. [0492] The TCR or the recombinant nucleic acid encoding the TCR can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, WSGR Docket No.50401-795.601 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more after the subject has been administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide. The immune cell comprising the TCR or the recombinant nucleic acid encoding the TCR can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more after the subject has been administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide. [0493] In some embodiments, the RAS polypeptide is administered at least 1 hour after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 2 hours after the subject has been administered the TCR or an immune cell comprising the TCR or an immune cell comprising the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 4 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 8 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 12 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 1 day after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 2 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 5 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 10 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 20 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 30 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 1 month after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 2 months after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 3 months after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 6 months after the subject has been administered the TCR or an immune cell comprising the TCR. In WSGR Docket No.50401-795.601 some embodiments, the RAS polypeptide is administered at least 1 year after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 2 years after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the RAS polypeptide is administered at least 3 years or more after the subject has been administered the TCR or an immune cell comprising the TCR. [0494] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 hour after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 4 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 8 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 12 hours after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 day after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 5 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 10 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 20 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 30 days after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 month after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 months after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 3 months after the subject has been administered the TCR or an immune cell comprising the TCR. In some WSGR Docket No.50401-795.601 embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 6 months after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 year after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 years after the subject has been administered the TCR or an immune cell comprising the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 3 years or more after the subject has been administered the TCR or an immune cell comprising the TCR. [0495] In some embodiments, the RAS polypeptide is administered at least 1 hour after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 2 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 4 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 8 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 12 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 1 day after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 2 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 5 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 10 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 20 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 30 days after the subject has been WSGR Docket No.50401-795.601 administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 1 month after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 2 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 3 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 6 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 1 year after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 2 years after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the RAS polypeptide is administered at least 3 years or more after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. [0496] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 hour after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 4 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 8 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 12 hours after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid WSGR Docket No.50401-795.601 encoding the RAS polypeptide is administered at least 1 day after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 5 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 10 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 20 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 30 days after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 month after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 3 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 6 months after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 year after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide is administered at least 2 years after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. In some embodiments, the recombinant nucleic acid encoding the RAS WSGR Docket No.50401-795.601 polypeptide is administered at least 3 years or more after the subject has been administered the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR. [0497] In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 hour after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 hours after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 4 hours after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 8 hours after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 12 hours after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 day after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 days after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 5 days after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 10 days after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 20 days after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 30 days after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 month after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 months after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 3 months after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 6 months after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 year after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 years after the subject has been administered the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 3 years or more after the subject has been administered the RAS polypeptide. WSGR Docket No.50401-795.601 [0498] In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 hour after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 hours after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 4 hours after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 8 hours after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 12 hours after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 day after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 days after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 5 days after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 10 days after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 20 days after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 30 days after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 month after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 months after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 3 months after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an WSGR Docket No.50401-795.601 immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 6 months after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 year after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 years after the subject has been administered the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 3 years or more after the subject has been administered the RAS polypeptide. [0499] In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 hour after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 4 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 8 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 12 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 day after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 5 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 10 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 20 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 30 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 month after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some WSGR Docket No.50401-795.601 embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 3 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 6 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 1 year after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 2 years after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the TCR or an immune cell comprising the TCR is administered at least 3 years or more after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. [0500] In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 hour after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 4 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 8 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 12 hours after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 day after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 5 days after the subject has WSGR Docket No.50401-795.601 been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 10 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic encoding the TCR is administered at least 20 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 30 days after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 month after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 3 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 6 months after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 1 year after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 2 years after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. In some embodiments, the recombinant nucleic acid encoding the TCR or an immune cell comprising the recombinant nucleic acid encoding the TCR is administered at least 3 years or more after the subject has been administered the recombinant nucleic acid encoding the RAS polypeptide. [0501] In some embodiments, the TCR is expressed by a cell. In some embodiments, the cell is an immune cell. In some embodiments, the recombinant nucleic acid encoding the TCR is expressed by a cell. In some embodiments, the cell is an immune cell. In some embodiments, the TCR is a soluble TCR. WSGR Docket No.50401-795.601 [0502] In some embodiments, the method comprises administering two or more different TCRs. In some embodiments, the method comprises administering two or more recombinant nucleic acids encoding the two or more different TCRs. In some embodiments, the two or more TCRs comprise a first TCR and a second TCR. In some embodiments, the two or more different TCRs are expressed on the surface of two different immune cells. In some embodiments, the first TCR and the second TCR bind to different peptide:MHC complexes, each peptide:MHC complex comprising (i) an epitope sequence and (ii) a human MHC encoded by an HLA allele. In some embodiments the two or more different TCRs are administered separately or co-administered in a same mixture. In some embodiments, recombinant nucleic acids encoding the two or more different TCRs are administered separately or co-administered in a same mixture. In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12V mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, and the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12D mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA- C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01. In some embodiments, the TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12V mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, and the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12C mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA- A*68:01, and HLA-C*03:03. In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12D mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01., and the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12C mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA- A*68:01, and HLA-C*03:03. [0503] In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05 and the second TCR binds to a peptide:MHC WSGR Docket No.50401-795.601 complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75- 79 and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01. In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01 and, HLA-A*03 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75-79 and an MHC encoded by an HLA allele selected from the group consisting of HLA- B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA- A*68:01 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. [0504] In some embodiments, the RAS polypeptide does not comprise a full-length RAS protein sequence. In some embodiments, the RAS polypeptide comprises a RAS epitope sequence. In some embodiments, the RAS epitope sequence comprises a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NOs: 58 or 59. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NOs: 58 or 59. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NOs: 58 or 59. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 59. In some cases, the HLA allele is an HLA-A allele. In some cases, the HLA allele is selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*03:02, HLA-A*03:05, HLA-B*40:01, and HLA-A*68:01. [0505] In some embodiments, the RAS epitope sequence comprises a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 60. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 60. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO 60. In some embodiments, the RAS epitope sequence comprises a WSGR Docket No.50401-795.601 sequence of SEQ ID NO: 60. In some embodiments, the HLA allele is an HLA-C allele. In some embodiments, the HLA allele is an HLA-C*01:02 allele. [0506] In some embodiments, the RAS epitope sequence comprises a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NOs: 61 or 62. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NOs: 61 or 62. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NOs: 61 or 62. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 61 or 62. In some embodiments, the HLA allele is an HLA-C allele. In some embodiments, the HLA allele is an HLA-C*03:03, or HLA-C*03:04. [0507] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NOs: 58 or 59. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NOs: 58 or 59. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NOs: 58 or 59. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 59. In some embodiments, the HLA allele is an HLA-A allele. In some embodiments, the HLA allele is an HLA-A*11:01. [0508] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 65-71. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 65-71. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 65-71. In some embodiments, the RAS epitope sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 65-71. In some embodiments, the HLA allele is an HLA-DRB1 allele. In some embodiments, the HLA allele is an HLA-DRB1*07:01. [0509] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NOs: 58 or 72. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NOs: 58 or 72. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NOs: 58 or 72. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 72. In some embodiments, the HLA allele is an HLA-A allele. In some embodiments, the HLA allele is selected from the group consisting of A*03:01, HLA-A*03:02, and HLA-A*03:05. WSGR Docket No.50401-795.601 [0510] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 75. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 75. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 75. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 75. In some embodiments, the HLA allele is an HLA-B allele. In some embodiments, the HLA allele is an HLA-B*07:02. In some embodiments, the HLA allele is an HLA- C allele. In some embodiments, the HLA allele is selected from the group consisting of HLA- C*08:02, HLA-C*03:04, and HLA-C*05:01. [0511] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 76. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 76. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 76. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 76. In some embodiments, the HLA allele is an HLA-A allele. In some embodiments, the HLA allele is selected from the group consisting of HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01. [0512] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 77. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 77. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 77. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 77. In some embodiments, the HLA allele is an HLA-A allele. In some embodiments, the HLA allele is HLA-A*11:01. [0513] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NOs: 78 or 79. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NOs: 78 or 79. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NOs: 78 or 79. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NOs: 78 or 79. In some embodiments, the HLA allele is an HLA-C allele. In some embodiments, the HLA allele is HLA-C*08:02. [0514] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 29. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 29. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to WSGR Docket No.50401-795.601 a sequence of SEQ ID NO: 29. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 29. In some embodiments, the HLA allele is an HLA-DRB1 allele. In some embodiments, the HLA allele is HLA-DRB1*11:01. [0515] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 81. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 81. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 81. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 81. In some embodiments, the HLA allele is an HLA-A allele. In some embodiments, the HLA allele is selected from a group consisting of HLA-A*3:01, HLA-A*11:01, and HLA-A*68:01. [0516] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 1096. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 1096. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 1096. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 1096. In some embodiments, the HLA allele is an HLA-A allele. In some embodiments, the HLA allele is selected from a group consisting of HLA- A*3:01, HLA-A*11:01, and HLA-A*68:01. [0517] In some embodiments, the RAS epitope sequence comprises a sequence with at least 70% sequence identity to a sequence of SEQ ID NO: 82. In some embodiments, the RAS epitope sequence comprises a sequence with at least 80% sequence identity to a sequence of SEQ ID NO: 82. In some embodiments, the RAS epitope sequence comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 82. In some embodiments, the RAS epitope sequence comprises a sequence of SEQ ID NO: 82. In some embodiments, the HLA allele is an HLA-C allele. In some embodiments, the HLA allele is HLA-C*03:03. [0518] In some embodiments, the RAS polypeptide comprises a multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise a full-length RAS polypeptide. In some embodiments, the sequence of the multiepitopic polypeptide is the same RAS epitope sequence. In some embodiments, the multiepitopic polypeptide comprises two or more different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 2 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 3 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 4 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 5 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide WSGR Docket No.50401-795.601 comprises at least 6 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 8 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 9 different RAS epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 10 or more different RAS epitope sequences. In some embodiments, the different RAS epitope sequences are separated. In some embodiments, the different RAS epitope sequences are separated by linker sequences. In some embodiments, the RAS polypeptide is a multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide is a RAS polypeptide. [0519] In some embodiments, antigen presenting cells (APCs) of subject administered the RAS polypeptide present a RAS epitope sequence as a peptide:MHC complex. In some embodiments, antigen presenting cells of subject administered the nucleic acid encoding the RAS polypeptide comprising the multiepitopic polypeptide present a RAS epitope sequence as a peptide:MHC complex. In some embodiments, the APCs present more of a RAS epitope as a peptide:MHC complex compared to the APCs of a subject administered a full length RAS polypeptide or recombinant nucleic acid encoding the full-length RAS polypeptide. [0520] In some embodiments, T cells of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide exhibit increased expansion compared to T cells of a subject administered a full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. [0521] In some embodiments, the multiepitopic polypeptide comprises a first RAS amino acid sequence comprising a first RAS epitope sequence. In some embodiments, the multiepitopic polypeptide comprises a second RAS amino acid sequence comprising a second RAS epitope sequence. In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence are different. In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence is separated by a linker. [0522] In some embodiments, the first amino acid sequence is the first epitope sequence. In some embodiments the second amino acid sequence is the second epitope sequence. In some embodiments, the first amino acid sequence is the first epitope sequence, and the second amino acid sequence is the second epitope sequence. In some embodiments, the first amino acid sequence consists of the first epitope sequence. In some embodiments, the second amino acid sequence consists of the second epitope sequence. In some embodiments, the first amino acid sequence consists of the first epitope sequence, and the second amino acid sequence consists of the second epitope sequence. [0523] In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation. In some embodiments, the second RAS amino acid sequence comprises a second RAS mutation. In some embodiments, the first RAS mutation is different from the second RAS mutation. In some WSGR Docket No.50401-795.601 embodiments, the first RAS amino acid sequence comprises a first RAS mutation, and the second RAS amino acid sequence comprises a second RAS mutation. In some embodiments, the first RAS amino acid sequence comprises a first RAS mutation, and the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation. In some embodiments, the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C. In some embodiments, the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C. In some embodiments, the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell. [0524] In some embodiments, the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell. In some embodiments, the first RAS mutation is G12V, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72. In some embodiments, the first RAS mutation is G12D, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79. In some embodiments, the first RAS mutation is G12C, and the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096. [0525] In some embodiments, the first RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide. In some embodiments, the second RAS epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length RAS polypeptide. [0526] In some embodiments, the first RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide. In some embodiments, the second RAS epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length RAS polypeptide. [0527] In some embodiments, the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker. In some embodiments, the first amino acid sequence comprises the first RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first RAS epitope sequence from the full length RAS polypeptide. In some embodiments, the second amino acid sequence comprises the second RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second RAS epitope sequence from the full length RAS polypeptide. WSGR Docket No.50401-795.601 [0528] In some embodiments, the multiepitopic polypeptide does not comprise more than 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more consecutive amino acids from the full-length RAS polypeptide. [0529] In some embodiments, the multiepitopic polypeptide comprises a first RAS epitope sequence. In some embodiments, the first RAS epitope sequence is operably linked to a second RAS epitope sequence. In some embodiments, the first RAS epitope sequence and the second RAS epitope sequence are the same. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are different. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are presentable by different HLA alleles. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are presented by different HLA alleles. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are predicted to bind to different HLA alleles. In some embodiments, the first RAS epitope sequence and second RAS epitope sequence are predicted to be presented by different HLA alleles. [0530] In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 500nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 400nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 300nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele. In some embodiments, a first RAS epitope sequence is predicted to bind to a first HLA allele. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 200nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 100nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 50nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD less than 1nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele. In some embodiments, a first RAS epitope sequence is predicted to bind to a second HLA allele. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 200nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 300nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 500nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 600nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 700nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 800nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 900nM. In some embodiments, a first RAS epitope sequence binds to a second HLA allele with a KD of more than 1000nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 1nM and binds to second HLA allele with WSGR Docket No.50401-795.601 a KD of more than 200nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 50nM and binds to second HLA allele with a KD of more than 300nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 100nM and binds to second HLA allele with a KD of more than 500nM. In some embodiments, a first RAS epitope sequence binds to a first HLA allele with a KD of less than 200 nM and binds to second HLA allele with a KD of more than 600nM. [0531] In some aspects, the first RAS epitope sequence is operably linked to the second RAS epitope sequence. In some aspects, the first RAS epitope sequence is operably linked to the second RAS epitope sequence via a linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0532] In some embodiments, the multiepitopic polypeptide comprises a first RAS epitope sequence, operably linked to a second RAS epitope sequence, operably linked to a third RAS epitope sequence. In some embodiments, the multiepitopic polypeptide comprises a first amino acid sequence comprising a first RAS epitope sequence, operably linked to a second amino acid sequence comprising a second RAS epitope sequence, operably linked to a third amino acid sequence comprising a third RAS epitope sequence. [0533] In some embodiments, the first RAS epitope sequence, the second RAS epitope sequence, or the third RAS epitope sequence comprises a RAS mutation selected from the group consisting of G12V, G12D, and G12C. In some embodiments, the first RAS epitope sequence, the second RAS epitope sequence, and the third RAS epitope sequence comprises a RAS mutation selected from the group consisting of G12V, G12D, and G12C. In some embodiments, the first RAS epitope sequence, the second RAS epitope sequence, and the third RAS epitope sequence comprise different RAS mutations. In some embodiments, the first RAS epitope sequence comprises a G12V mutation. In some embodiments, the first RAS epitope sequence comprises a G12D mutation. In some embodiments, the first RAS epitope sequence comprises a G12C mutation. In some embodiments, the second RAS epitope sequence comprises a G12V mutation. In some embodiments, the second RAS epitope sequence comprises a G12D mutation. In some embodiments, the second RAS epitope sequence comprises a G12C mutation. In some embodiments, the third RAS epitope sequence comprises a G12V mutation. In some embodiments, the third RAS epitope sequence comprises a G12D mutation. In some embodiments, the third RAS epitope sequence comprises a G12C mutation. WSGR Docket No.50401-795.601 [0534] In some embodiments, the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05. In some embodiments, the first RAS epitope sequence is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA- C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05. In some embodiments, the first RAS epitope sequence binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA- A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA- A*03:02, and HLA-A*03:05. In some embodiments, the first RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA- A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA- C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05. In some embodiments, the first RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05. [0535] In some embodiments, the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA- C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02. In some embodiments, the second RAS epitope sequence is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02. In some embodiments, the second RAS epitope sequence binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02. In some embodiments, the second RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA- C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02. In some embodiments, the second RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA- C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02. [0536] In some embodiments, the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. In some embodiments, the third RAS epitope WSGR Docket No.50401-795.601 sequence is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. In some embodiments, the third RAS epitope sequence binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. In some embodiments, the third RAS epitope sequence is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. In some embodiments, the third RAS epitope sequence is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. [0537] In some cases, the subject does not express an HLA that binds to each RAS epitope of the multiepitopic polypeptide. In some cases, the subject only expresses HLA alleles that bind to a subset of RAS epitope sequences of the multiepitopic polypeptide. [0538] In some embodiments, the RAS polypeptide comprises a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27- 29. In some embodiments, the RAS polypeptide comprises a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises a sequence with at least 90% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 27- 29. [0539] In some embodiments, the RAS polypeptide comprises a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises a sequence with at least 70% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises a sequence with at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises a sequence selected from the group consisting of SEQ ID NOs: 27-29. WSGR Docket No.50401-795.601 [0540] In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0541] In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 70% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27- 29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises one or more copies of a sequence selected from the group consisting of SEQ ID NOs: 27-29. [0542] In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of one or more sequences with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. WSGR Docket No.50401-795.601 [0543] In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 70% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of a sequence with at least 80% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of one or more sequences with at least 90% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises two copies of each sequence of SEQ ID NOs: 27-29. [0544] In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of one or more sequences with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0545] In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 70% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of a sequence with at least 80% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of one or more sequences with at least 90% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises three copies of each sequence of SEQ ID NOs: 27-29. [0546] In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least WSGR Docket No.50401-795.601 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of one or more sequences with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0547] In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 70% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of a sequence with at least 80% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of one or more sequences with at least 90% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises four copies of each sequence of SEQ ID NOs: 27-29. [0548] In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of one or more sequences with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0549] In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 70% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of a sequence with at least 80% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of one or more sequences with at least 90% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises five copies of each sequence of SEQ ID NOs: 27-29. WSGR Docket No.50401-795.601 [0550] In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 70% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 80% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of one or more sequences with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. [0551] In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 70% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of a sequence with at least 80% sequence identity to each sequence of SEQ ID NOs: 27- 29. In some embodiments, the RAS polypeptide comprises six or more copies of one or more sequences with at least 90% sequence identity to each sequence of SEQ ID NOs: 27-29. In some embodiments, the RAS polypeptide comprises six or more copies of each sequence of SEQ ID NOs: 27-29. [0552] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28. In some cases, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 28. [0553] In some cases, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a WSGR Docket No.50401-795.601 sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 via a linker. In some cases, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 29 via a linker, and the sequence of SEQ ID NO: 29 operably linked to the sequence of SEQ ID NO: 28 via a linker. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0554] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27. [0555] In some cases, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, WSGR Docket No.50401-795.601 at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 via a linker. In some cases, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 operably linked to the sequence of SEQ ID NO: 27 via a linker. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0556] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 29. [0557] In some cases, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 via a linker. In some cases, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 operably linked to the sequence of SEQ ID NO: 29 via a linker. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence WSGR Docket No.50401-795.601 having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0558] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29. In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 29. [0559] In some cases, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 via a linker. In some cases, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 operably linked to the sequence of SEQ ID NO: 29 via a linker. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence WSGR Docket No.50401-795.601 identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0560] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 27. [0561] In some cases, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29 operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 via a linker. In some cases, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 28, operably linked to the sequence of SEQ ID NO: 29 via a linker, and the sequence of SEQ ID NO: 29 operably linked to the sequence of SEQ ID NO: 27 via a linker. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0562] In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably WSGR Docket No.50401-795.601 linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28. In some embodiments, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 27, operably linked to the sequence of SEQ ID NO: 28. [0563] In some cases, the RAS polypeptide comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 via a linker, and the sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27 operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28 via a linker. In some cases, the RAS polypeptide comprises, from N terminus to C terminus, the sequence of SEQ ID NO: 29, operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 operably linked to the sequence of SEQ ID NO: 28 via a linker. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0564] In some embodiments, the RAS polypeptide comprises at least two copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, and operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27. In some WSGR Docket No.50401-795.601 embodiments, the RAS polypeptide comprises at least two copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises three copies of the multiepitopic polypeptide. In some embodiments, the RAS polypeptide comprises five copies of the multiepitopic polypeptide. [0565] In some embodiments, the RAS polypeptide comprises at three copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, and operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises at three copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. [0566] In some embodiments, the RAS polypeptide comprises at four copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, and operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises at four copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. [0567] In some embodiments, the RAS polypeptide comprises at five copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 29, operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at WSGR Docket No.50401-795.601 least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 28, and operably linked to a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to the sequence of SEQ ID NO: 27. In some embodiments, the RAS polypeptide comprises at five copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. [0568] In some embodiments, the RAS polypeptide further comprises a secretory domain (Sec) sequence. In some embodiments, the Sec sequence is at the N terminus of the multiepitopic polypeptide. In some embodiments, the Sec comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 32. In some embodiments, the Sec sequence comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 32. In some embodiments the Sec sequence comprises a sequence of SEQ ID NO: 32. [0569] In some cases, the Sec sequence is operably linked to the multiepitopic polypeptide. In some embodiments, the Sec sequence is operably linked to the multiepitopic polypeptide via a linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 30. In some embodiments, the linker comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 30. In some cases, the linker comprises a sequence of SEQ ID NO: 30. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 31. In some cases, the linker comprises a sequence of SEQ ID NO: 31. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 112. In some cases, the linker comprises a sequence of SEQ ID NO: 112. [0570] In some embodiments, the RAS polypeptide further comprises an MHC Class I trafficking domain (MITD) sequence. In some embodiments, the MITD sequence is at the C terminus of the multiepitopic polypeptide. In some embodiments, the MITD sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 33. In some embodiments, the MITD sequence comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: WSGR Docket No.50401-795.601 33. In some embodiments the Sec sequence comprises a sequence of SEQ ID NO: 33. In some embodiments, the multiepitopic polypeptide is operably linked to the MITD sequence via a linker. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 30. In some embodiments, the linker comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 30. In some cases, the linker comprises a sequence of SEQ ID NO: 30In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 112. In some embodiments, the linker comprises a sequence of SEQ ID NO: 112. [0571] In some embodiments, the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to sequence identity to a sequence of SEQ ID NO: 25. In some embodiments, the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to sequence identity to a sequence of SEQ ID NO: 26. In some embodiments, the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to sequence identity to a sequence of SEQ ID NO: 113. [0572] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 14. [0573] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the WSGR Docket No.50401-795.601 recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 15. [0574] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 16. [0575] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 17. [0576] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence WSGR Docket No.50401-795.601 having at least 60% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 18. [0577] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 19. [0578] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 20. [0579] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 21. In some WSGR Docket No.50401-795.601 embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 21. [0580] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 70% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 22. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences with at least 90% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 9. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic WSGR Docket No.50401-795.601 acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 22. [0582] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises a sequence of SEQ ID NO: 22. [0583] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100- 102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS WSGR Docket No.50401-795.601 polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 22. [0584] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences with at least 90% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104- 106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ WSGR Docket No.50401-795.601 ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence with at least 90% sequence identity to a sequence of SEQ ID NO: 22. [0585] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14- 23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of a sequence of SEQ ID NO: 22. [0586] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid WSGR Docket No.50401-795.601 encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises two copies of a sequence of SEQ ID NO: 22. [0587] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of a sequence of SEQ ID NO: 22. [0588] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of a sequence of SEQ ID NO: 22. WSGR Docket No.50401-795.601 [0589] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of a sequence of SEQ ID NO: 22. [0590] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 15. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 16. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 17. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 18. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 19. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 20. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 21. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of a sequence of SEQ ID NO: 22. [0591] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of WSGR Docket No.50401-795.601 SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence a having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109. [0592] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109. [0593] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence of any one of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109. [0594] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 operably linked to a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence. [0595] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% WSGR Docket No.50401-795.601 sequence identity to any one of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence. [0596] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence and the sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 operably linked to a sequence of any one of SEQ ID NO: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence. [0597] In some embodiments, the linker sequence encodes a cleavable linker. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence of SEQ ID NO: 13. WSGR Docket No.50401-795.601 [0598] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. [0599] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14- 16, 84, 92, 96, 100, 104, and 108. [0600] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence of any one of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108. [0601] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence. [0602] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence WSGR Docket No.50401-795.601 identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence. [0603] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, via a linker sequence and the sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence. [0604] In some embodiments, the linker sequence encodes a cleavable linker. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13. [0605] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 60%, at WSGR Docket No.50401-795.601 least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110. [0606] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110. [0607] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence of any one of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110. [0608] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence and the sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence. [0609] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence and the sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence. WSGR Docket No.50401-795.601 [0610] In some cases, the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, via a linker sequence and the sequence of any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence of any one of SEQ ID NO: 20-23, 88, 94, 98, 102, 106, and 110, via a linker sequence. [0611] In some embodiments, the linker sequence encodes a cleavable linker. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 5. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 6. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 9. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 11. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 12. In some embodiments, the linker sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 13. [0612] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises at least two copies of a string of sequences. In some embodiments, each string of sequences comprises, from 5’ end to 3’ end, a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 60%, at least 65%, at least 70%, at least 75%, WSGR Docket No.50401-795.601 at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. In some embodiments, each string of sequences comprises, from 5’ end to 3’ end, a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. In some embodiments, each string of sequences comprises, from 5’ end to 3’ end, a sequence of any one of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence of any one of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence of any one of SEQ ID NO: 14-16, 84, 92, 96, 100, 104, and 108. [0613] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises four copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises six copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises seven copies of the string of sequences. In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide comprises eight copies of the string of sequences. [0614] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a secretory (Sec) sequence. In some embodiments, the Sec sequence is at the 5’ end of the string of sequences. In some embodiments the Sec sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 3. In some embodiments, the string of sequences is operably linked to the Sec sequence. In some embodiments, the string of sequences is operably linked to the Sec sequence via a linker sequence. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 4. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 7. In some embodiments, the linker comprises a sequence of SEQ ID NO: 4. In some embodiments, the linker comprises a sequence of SEQ ID NO: 7. [0615] In some embodiments, the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MHC I Trafficking Domain (MITD) sequence. In some embodiments, the sequence encoding an MITD sequence is at the 3’ end of the string of sequences. In WSGR Docket No.50401-795.601 some embodiments the MITD sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 24 or 90. In some embodiments, the string of sequences is operably linked to the MITD sequence. In some embodiments, the string of sequences is operably linked to the MITD sequence via a linker sequence. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 4. In some embodiments, the linker comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 7. In some embodiments, the linker comprises a sequence of SEQ ID NO: 4. In some embodiments, the linker comprises a sequence of SEQ ID NO: 7. [0616] In some embodiments, the recombinant nucleic acid is codon optimized. In some embodiments, the recombinant nucleic acid is not codon optimized. In some embodiments, the recombinant nucleic acid is DNA. In some embodiments, the recombinant nucleic acid is RNA. In some embodiments the recombinant nucleic acid is mRNA. [0617] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 95. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 103. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at WSGR Docket No.50401-795.601 least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 111. [0618] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 95. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 103. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence of SEQ ID NO: 111. [0619] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 95. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 103. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 111. [0620] In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 2. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 91. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 95. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 103. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 111. WSGR Docket No.50401-795.601 [0621] In some embodiments, the subject expresses more of the RAS epitope when administered with the codon optimized recombinant nucleic acid than administered with wild-type recombinant nucleic acid. [0622] In some embodiments, the TCR comprises a beta chain construct. In some embodiments, the TCR comprises an alpha chain construct. In some embodiments, the TCR comprises a beta chain construct and an alpha chain construct. In some embodiments, the TCR beta chain construct comprises a complementarity determining region 3 (CDR3). In some embodiments the TCR beta chain construct comprises a CDR3 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 57. In some embodiments the TCR beta chain construct comprises a CDR3 having an amino acid sequence set forth in SEQ ID NO: 57. In some embodiments, the TCR beta chain construct comprises a variable region. In some embodiments the TCR beta chain construct comprises a variable region having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 52 or SEQ ID NO: 53. In some embodiments, the TCR beta chain construct comprises a CDR1. In some embodiments, the TCR beta chain construct comprises a CDR1 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 55. In some embodiments, the TCR beta chain construct comprises a CDR1 having an amino acid set forth in SEQ ID NO: 55. In some embodiments, the TCR beta chain construct comprises a CDR2. In some embodiments, the TCR beta chain construct comprises a CDR2 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 56. In some embodiments, the TCR beta chain construct comprises a CDR2 having an amino acid sequence set forth in SEQ ID NO: 56. [0623] In some embodiments, the TCR comprises an alpha chain construct. In some embodiments, the alpha chain construct comprises a CDR1. In some embodiments, the alpha chain construct comprises a CDR2. In some embodiments, the alpha chain construct comprises a CDR3. In some embodiments, the alpha chain construct comprises a CDR1 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 46. In some embodiments, the alpha chain construct comprises a CDR1 having an amino acid sequence set forth in SEQ ID NO: 46. In some embodiments, the alpha chain construct comprises a CDR2 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 47. In some embodiments, the alpha chain construct comprises a CDR2 having an amino acid sequence set forth in SEQ ID NO: 47. In some embodiments, the alpha chain construct comprises a CDR3 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 100. In some embodiments, the alpha chain construct comprises a CDR3 having an amino acid WSGR Docket No.50401-795.601 sequence set forth in SEQ ID NO: 48. In some embodiments, the alpha chain construct comprises a variable region. In some embodiments the alpha chain construct comprises a variable region having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44. In some embodiments the alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44. [0624] In some embodiments the TCR comprises a beta chain having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 49 or SEQ ID NO: 51. In some embodiments, the TCR comprises a beta chain having an amino acid sequence set forth in SEQ ID NO: 49 or SEQ ID NO: 51. In some embodiments, the TCR comprises an alpha chain having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 40 or SEQ ID NO: 42. In some embodiments, the TCR comprises an alpha chain having an amino acid sequence set forth in SEQ ID NO: 40 or SEQ ID NO: 42. [0625] In some embodiments, the TCR comprises a beta chain construct. In some embodiments, the TCR comprises an alpha chain construct. In some embodiments, the TCR comprises a beta chain construct and an alpha chain construct. In some embodiments, the TCR beta chain construct comprises a complementarity determining region 3 (CDR3). In some embodiments the TCR beta chain construct comprises a CDR3 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one of TCR beta chain CDR3 presented in Tables 8A-8D. In some embodiments the TCR beta chain construct comprises a CDR3 having an amino acid sequence of any one TCR beta chain CDR3 presented in Tables 8A-8D. In some embodiments, the TCR beta chain construct comprises a variable region. In some embodiments the TCR beta chain construct comprises a variable region having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR beta variable domain presented in Tables 8A-8D. In some embodiments, the TCR beta chain construct comprises a CDR1. In some embodiments, the TCR beta chain construct comprises a CDR1 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR beta chain CDR1 presented in Tables 8A-8D. In some embodiments, the TCR beta chain construct comprises a CDR1 having an amino acid sequence of any one TCR beta chain CDR1 presented in Tables 8A-8D. In some embodiments, the TCR beta chain construct comprises a CDR2. In some embodiments, the TCR beta chain construct comprises a CDR2 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence any one TCR beta chain CDR2 presented in Tables 8A-8D. In some embodiments, the TCR beta chain WSGR Docket No.50401-795.601 construct comprises a CDR2 having an amino acid sequence of any one TCR beta chain CDR2 presented in Tables 8A-8D. [0626] In some embodiments, the TCR comprises an alpha chain construct. In some embodiments, the alpha chain construct comprises a CDR1. In some embodiments, the alpha chain construct comprises a CDR2. In some embodiments, the alpha chain construct comprises a CDR3. In some embodiments, the alpha chain construct comprises a CDR1 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR alpha chain CDR1 presented in Tables 8A-8D. In some embodiments, the alpha chain construct comprises a CDR1 having an amino acid sequence of any one TCR alpha chain CDR1 presented in Tables 8A- 8D. In some embodiments, the alpha chain construct comprises a CDR2 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR alpha chain CDR2 presented in Tables 8A-8D. In some embodiments, the alpha chain construct comprises a CDR2 having an amino acid sequence of any one TCR alpha chain CDR2 presented in Tables 8A-8D. In some embodiments, the alpha chain construct comprises a CDR3 having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR alpha chain CDR3 presented in Tables 8A-8D. In some embodiments, the alpha chain construct comprises a CDR3 having an amino acid sequence of any one TCR alpha chain CDR3 presented in Tables 8A-8D. In some embodiments, the alpha chain construct comprises a variable region. In some embodiments the alpha chain construct comprises a variable region having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR alpha variable domain presented in Tables 8A-8D. In some embodiments the alpha chain construct comprises a variable region having an amino acid sequence of any one TCR alpha variable domain presented in Tables 8A-8D. [0627] In some embodiments the TCR comprises a beta chain having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR beta chain presented in Tables 8A-8D. In some embodiments, the TCR comprises a beta chain having an amino acid sequence of any one TCR beta chain presented in Tables 8A-8D. In some embodiments, the TCR comprises an alpha chain having an amino acid sequence with at least 60%, 70%, 80%, or 90% sequence identity to an amino acid sequence of any one TCR alpha chain presented in Tables 8A-8D. In some embodiments, the TCR comprises an alpha chain having an amino acid sequence of any one TCR alpha chain presented in Tables 8A-8D. [0628] Table 8A. Exemplary TCRs WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 [0629] Table 8B. Exemplary TCRs WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 [0630] Table 8C. Exemplary TCRs WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 [0631] Table 8D. Exemplary TCRs WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 [0632] Provided herein is a method of treating a subject with a disease or condition. In some embodiments, the disease or condition is a cancer. In some embodiments, the method comprises administering to the subject a therapy. In some embodiments, the therapy comprises a multiepitopic polypeptide. In some embodiments, the therapy comprises a recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the therapy comprises a cell comprising the multiepitopic polypeptide. In some embodiments, the therapy comprises a cell comprising the recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide comprises a first amino acid sequence comprising a first epitope sequence from a cancer protein. In some embodiments, the multiepitopic polypeptide comprises a second amino acid sequence comprising a second epitope sequence from the cancer protein. In some embodiments, the first epitope sequence and the second epitope sequence are the same. In some embodiments, the first epitope sequence and the second epitope sequence are different. In some embodiments, the first epitope sequence or the second epitope sequence are linked by a linker. In some embodiments, the multiepitopic polypeptide does not comprise the full-length cancer protein. In some embodiments, the subject has been previously treated with a TCR. In some embodiments, the subject has been previously treated with a recombinant acid encoding the TCR. In some embodiments, the TCR recognizes and binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises the first epitope sequence and a human MHC encoded by an HLA allele. In some embodiments, the peptide:MHC complex comprises the second epitope sequence and a human MHC encoded by an HLA allele. [0633] Provided herein is a method of treating a subject with a disease or condition. In some embodiments, the disease or condition is a cancer. In some embodiments, the method comprises administering to the subject a therapy. In some embodiments, the therapy comprises a TCR. In some embodiments, the therapy comprises a recombinant nucleic acid encoding the TCR. In some embodiments, the therapy comprises a cell comprising the TCR. In some embodiments, the therapy comprises a cell comprising a recombinant nucleic acid encoding the TCR. In some embodiments, the TCR recognizes and binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises an epitope sequence form a cancer protein and a human MHC encoded by an HLA allele. In some embodiments, the subject has been previously treated with a multiepitopic polypeptide. In some embodiments, the subject has been previously treated with a recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the subject has been previously treated with a cell comprising a multiepitopic polypeptide. In some embodiments, the WSGR Docket No.50401-795.601 subject has been previously treated with a cell comprising a recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide comprises a first amino acid sequence comprising a first epitope sequence from a cancer protein. In some embodiments, the multiepitopic polypeptide comprises a second amino acid sequence comprising a second epitope sequence from the cancer protein. In some embodiments, the first epitope sequence and the second epitope sequence are the same. In some embodiments, the first epitope sequence and the second epitope sequence are different. In some embodiments, the first epitope sequence or the second epitope sequence are linked by a linker. In some embodiments, the multiepitopic polypeptide does not comprise the full-length cancer protein. In some embodiments the first epitope sequence or the second epitope sequence is the epitope sequence recognized by the TCR. [0634] Provided herein is a method of treating a subject with a disease or condition. In some embodiments, the disease or condition is a cancer. In some embodiments, the method comprises administering to the subject a first therapy. In some embodiments the first therapy comprises a multiepitopic polypeptide. In some embodiments, the first therapy comprises a recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the first therapy comprises a cell comprising a multiepitopic polypeptide. In some embodiments, the first therapy comprises a cell comprising a recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide comprises a first amino acid sequence comprising a first epitope sequence from a cancer protein. In some embodiments, the multiepitopic polypeptide comprises a second amino acid sequence comprising a second epitope sequence from the cancer protein. In some embodiments, the first epitope sequence and the second epitope sequence are the same. In some embodiments, the first epitope sequence and the second epitope sequence are different. In some embodiments, the first epitope sequence or the second epitope sequence are linked by a linker. In some embodiments, the multiepitopic polypeptide does not comprise the full-length cancer protein. In some embodiments, the method comprises administering to the subject a second therapy. In some embodiments, the second therapy comprises a TCR. In some embodiments, the second therapy comprises a recombinant nucleic acid encoding the TCR. In some embodiments, the second therapy comprises a cell comprising a TCR. In some embodiments, the second therapy comprises a cell comprising a recombinant nucleic acid encoding the TCR. In some embodiments, the TCR recognizes and binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises the first epitope sequence and a human MHC encoded by an HLA allele. In some embodiments, the peptide:MHC complex comprises the second epitope sequence and a human MHC encoded by an HLA allele. In some embodiments, the first therapy is administered prior to the second therapy. In some embodiments, the first therapy is administered concurrently with the second therapy. In some embodiments, the first therapy is administered subsequent to the second therapy. In some WSGR Docket No.50401-795.601 embodiments, presentation of the first and/or second epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject is higher than the presentation of the first and/or second epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length cancer protein or a recombinant nucleic acid encoding the full-length cancer protein. In some embodiments, the cancer protein is RAS. In some embodiments, the TCR recognizes an epitope derived from the cancer protein. [0635] In some embodiments, the method comprises administering two or more different TCRs. In some embodiments, the method comprises administering two or more recombinant nucleic acids encoding the two or more different TCRs. In some embodiments, the two or more TCRs comprise a first TCR and a second TCR. In some embodiments, the two or more different TCRs are expressed on the surface of two different immune cells. In some embodiments, the first TCR and the second TCR bind to different peptide:MHC complexes, each peptide:MHC complex comprising (i) an epitope sequence and (ii) a human MHC encoded by an HLA allele. In some embodiments the two or more different TCRs are administered separately or co-administered in a same mixture. In some embodiments, recombinant nucleic acids encoding the two or more different TCRs are administered separately or co-administered in a same mixture. In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75-79 and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01. In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 27, 58- 62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA- A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA- C*03:03, HLA-C*03:04, HLA-DRB1*07:01 and, HLA-A*03 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. In some embodiments, the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75-79 and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01 and the second TCR binds to a peptide:MHC WSGR Docket No.50401-795.601 complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting HLA- DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. [0636] In some embodiments, the APCs of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide present more of an epitope sequence derived from the cancer protein as a peptide:MHC complex compared to the APCs of a subject administered a full-length cancer protein. In some embodiments, the T cells of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide exhibit increased expansion compared to T cells of a subject administered a full-length cancer protein or a recombinant nucleic acid encoding the full-length cancer protein. In some embodiments, the cell is an APC. In some embodiments, the APC has been incubated with the multiepitopic polypeptide. In some embodiments, the APC has been incubated with the recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide comprises at least 2, 3, 4, 5, or more different epitope sequences derived from a cancer protein. [0637] In some embodiments, binding of the TCR to the peptide:MHC complex results in production of a cytokine by the immune cell. In some embodiments, the cytokine is IFN-γ. In some embodiments, the cytokine is IL-2. In some embodiments, the cytokine is TNF-α. In some embodiments, production of the cytokine is increased by about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% or more compared to an otherwise identical TCR recognizing an irrelevant peptide:MHC complex. In some embodiments, production of the cytokine is increased by about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% or more compared to an otherwise identical APC presenting a wild type RAS antigen. T Cell Activation [0638] The methods and compositions disclosed herein can comprise RAS-specific T cells that can be delivered to a subject having cancer. RAS -specific T cells can be generated by NEO-STIM, a process of T cell activation and/or expansion. [0639] Generating antigen specific (e.g., RAS -specific) T cells by controlled ex vivo induction or expansion of T cells (e.g., autologous T cells) can provide highly specific and beneficial T cell and T- cell receptors (TCRs). The present disclosure provides T cell manufacturing methods, TCRs, therapeutic T cell compositions which can be used for treating cancer. For example, the TCRs can be used for validating a whether its cognate epitope sequence is presented by a cell of interest and can be used for validating whether a candidate antigen is suitable for use as a part of a vaccine design. To obtain such TCRs, the first step is to expand and induce antigen specific T cells with a favorable phenotype and function. The present disclosure provides compositions and methods for WSGR Docket No.50401-795.601 manufacturing of T cells which can be used for antigen specific T cell therapy (e.g., personal or personalized T cell therapies for treating cancer). The T cell compositions provided herein can be personal antigen specific T cell therapies. The process includes on one hand, identification of the cancer-specific antigens, leading to the production of antigenic peptides or mRNAs encoding such antigenic peptides; and on the other hand, preparing activated, antigen specific cells for immunotherapy and identification of functional TCRs that can be used in TCR recognition assays as described herein. Preparing Activated, Antigen-specific T Cells [0640] The NEO-STIM process can comprise methods of preparing activated, antigen-specific T cells. [0641] Provided herein are methods for stimulating T cells. For example, the methods provided herein can be used to stimulate antigen specific T cells. The methods provided herein can be used to induce or activate T cells. For example, the methods provided herein can be used to expand activated T cells. For example, the methods provided herein can be used to induce naïve T cells. For example, the methods provided herein can be used to expand antigen specific CD8+ T cells. For example, the methods provided herein can be used to expand antigen specific CD4+ T cells. For example, the methods provided herein can be used to expand antigen specific CD8+ T cells having memory phenotype. For example, the therapeutic compositions can comprise antigen specific CD8+ T cells. For example, the therapeutic compositions can comprise antigen specific memory T cells. [0642] T cells can be activated ex vivo with a composition comprising antigenic peptides or polynucleotides encoding the antigenic peptides. [0643] T cells can be activated ex vivo with a composition comprising antigen loaded antigen- presenting cells. [0644] In some embodiments, the APCs and/or T cells are derived from a biological sample which is obtained from a subject. [0645] In some embodiments, the APCs and/or T cells are derived from a biological sample which is peripheral blood mononuclear cells (PBMC). [0646] In some embodiments, the subject is administered FLT3L prior to obtaining the biological sample for preparing the APCs and/or T cells. [0647] In some embodiments, the APCs and/or T cells are derived from a biological sample, for example, from healthy human donors. [0648] In some embodiments antigen-presenting cells are first loaded with antigenic peptides ex vivo and used to prepare antigen activated T cells. In some embodiments, the compositions provided herein comprise T cells that are stimulated by APCs, such as APCs pre-loaded with antigen peptides. The compositions can comprise a population of immune cells comprising T cells from a sample (e.g., a WSGR Docket No.50401-795.601 biological sample), wherein the T cells comprise APC-stimulated T cells. In some embodiments, mRNA encoding one or more antigenic peptides are introduced into APCs for expression of the antigenic peptides. Such APCs are used for stimulating or activating T cells. [0649] In some embodiments, the biological sample comprises a percentage of the at least one antigen specific T cell in the composition is at least about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%. In some embodiments, the biological sample comprises less than 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%.1%, 2%, 3%, 4%, 5%, or less than 10% antigen activated T cells of the total cell count in the biological sample that is derived from peripheral blood or leukapheresis. In some embodiments, the biological sample comprises less than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30% antigen activated T cells of the total cell count in the biological sample that is derived from peripheral blood. [0650] In some embodiments, the biological sample comprises antigen naive T cells. In some embodiments, the biological sample comprises greater than about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% antigen naive cells of the total cell count in the biological sample that is derived from peripheral blood or leukapheresis. [0651] In some embodiments, a percentage of at least one antigen specific CD8+ T cell in the composition is less than about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5% in the biological sample derived from peripheral blood or leukapheresis. In some embodiments, a percentage of at least one antigen specific CD4+ T cell in the composition is at least about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, of in the biological sample derived from peripheral blood or leukapheresis. [0652] In some embodiments, a percentage of the at least one antigen specific T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of the total immune cells. In some embodiments, a percentage of at least one antigen specific CD8+ T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of the total immune cells. In some embodiments, a percentage of at least one antigen specific CD4+ T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of the total immune cells. In some embodiments, a percentage of antigen specific T cells in the biological sample is at most about 0.5%. In some embodiments, a percentage of antigen specific WSGR Docket No.50401-795.601 CD8+ T cells in the biological sample is at most about 0.5%. In some embodiments, a percentage of antigen specific CD4+ T cells in the biological sample is at most about 0.5% in the biological sample. Preparing antigen loaded APCs [0653] The NEO-STIM process can comprise methods of preparing antigen loaded APCs. [0654] In some embodiments, a composition comprises a population of immune cells that has been incubated with one or more cytokines, growth factors or ligands, such as a ligand that binds to a cell surface receptor of an APC or a T cell. Examples of such cytokines, growth factors and ligands include, for example, GM-CSF, IL-4, IL-7, FLT3L, TNF-α, IL-1β, IL-15, PGE1, IL-6, IFN-α, INF-γ, R848, LPS, ss-rna40, and poly(I:C). In some embodiments, a composition comprises a population of immune cells that has been incubated with one or more APCs or APC preparations. For example, a composition can comprise a population of immune cells that has been incubated with one or more cytokine, growth factor and/or ligand stimulated APCs or cytokine, growth factor and/or ligand stimulated APC preparations. For example, a composition can comprise a population of immune cells that has been incubated with one or more cytokine stimulated APCs or cytokine stimulated APC preparations. For example, a composition can comprise a population of immune cells that have been incubated with one or more growth factor stimulated APCs or growth factor stimulated APC preparations. For example, a composition can comprise a population of immune cells that has been incubated with one or more ligand stimulated APCs or ligand stimulated APC preparations. [0655] In some embodiments, the APC is an autologous APC, an allogenic APC, or an artificial APC. In some embodiments, the APC is an artificial APC. [0656] Immune cells can be characterized by cell surface molecules. In some embodiments the immune cells are preferably selected based on the cell surface markers, for example, from the biological sample, by using antibodies that can bind to the cell surface receptors. In some embodiments some cells are negatively selected to enrich one or more cell types that do not express the cell surface molecule that they are negatively selected for. [0657] In some embodiments, antigen-presenting cells (APCs) are prepared from the biological sample by selecting from APCs or precursor cells that can be cultured in presence of antigenic peptides to generate antigen-loaded APCs, which are used for activating T cells. Some of the related cell surface markers for selecting and/or enriching for a set of cells is described below. [0658] CD1 (cluster of differentiation 1) is a family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells. [0659] CD11b or Integrin alpha M (ITGAM) is one protein subunit that forms heterodimeric integrin alpha-M beta-2 (αMβ2) molecule, also known as macrophage-1 antigen (Mac-1) or complement receptor 3(CR3). ITGAM is also known as CR3A, and cluster of WSGR Docket No.50401-795.601 differentiation molecule 11b (CD11b). The second chain of αMβ2 is the common integrin β2 subunit known as CD18, and integrin αMβ2 thus belongs to the β2 subfamily (or leukocyte) integrins. αMβ2 is expressed on the surface of many leukocytes involved in the innate immune system, including monocytes, granulocytes, macrophages, and natural killer cells. It mediates inflammation by regulating leukocyte adhesion and migration and has been implicated in several immune processes such as phagocytosis, cell-mediated cytotoxicity, chemotaxis and cellular activation. It is involved in the complement system due to its capacity to bind inactivated complement component 3b (iC3b). The ITGAM (alpha) subunit of integrin αMβ2 is directly involved in causing the adhesion and spreading of cells but cannot mediate cellular migration without the presence of the β2 (CD18) subunit. [0660] CD11c, also known as Integrin, alpha X (complement component 3 receptor 4 subunit) (ITGAX), is a gene that encodes for CD11c. CD11c is an integrin alpha X chain protein. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This protein combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as inactivated-C3b (iC3b) receptor 4 (CR4). The alpha X beta 2 complex seems to overlap the properties of the alpha M beta 2 integrin in the adherence of neutrophils and monocytes to stimulated endothelium cells, and in the phagocytosis of complement coated particles. CD11c is a type I transmembrane protein found at high levels on most human dendritic cells, but also on monocytes, macrophages, neutrophils, and some B cells that induces cellular activation and helps trigger neutrophil respiratory burst; expressed in hairy cell leukemias, acute nonlymphocytic leukemias, and some B-cell chronic lymphocytic leukemias. [0661] CD14 is a surface antigen that is preferentially expressed on monocytes/macrophages. It cooperates with other proteins to mediate the innate immune response to bacterial lipopolysaccharide. Alternative splicing results in multiple transcript variants encoding the same protein. CD14 exists in two forms, one anchored to the membrane by a glycosylphosphatidylinositol tail (mCD14), the other a soluble form (sCD14). Soluble CD14 either appears after shedding of mCD14 (48 kDa) or is directly secreted from intracellular vesicles (56 kDa). CD14 acts as a co-receptor (along with the Toll-like receptor TLR 4 and MD-2) for the detection of bacterial lipopolysaccharide (LPS). CD14 can bind LPS only in the presence of lipopolysaccharide-binding protein (LBP). Although LPS is considered its main ligand, CD14 also recognizes other pathogen-associated molecular patterns such as lipoteichoic acid. [0662] CD25 is expressed by conventional T cells after stimulation, and it has been shown that in human peripheral blood, only the CD4+CD25hi T cells are 'suppressors'. [0663] In some embodiments, the APC comprises a dendritic cell (DC). In some embodiments, the APC is derived from a CD14+ monocyte. In some embodiments, the APCs can be obtained from skin, spleen, bone marrow, thymus, lymph nodes, peripheral blood, or cord blood. In some embodiments, WSGR Docket No.50401-795.601 the CD14+ monocyte is from a biological sample from a subject comprising PBMCs. For example, a CD14+ monocyte can be isolated from, enriched from, or purified from a biological sample from a subject comprising PBMCs. In some embodiments, the CD14+ monocyte is stimulated with one or more cytokines or growth factors. In some embodiments, the one or more cytokines or growth factors comprise GM-CSF, IL-4, FLT3L, TNF-α, IL-1β, PGE1, IL-6, IL-7, IL-15, IFN-γ, IFN-α, R848, LPS, ss-rna40, poly I:C, or a combination thereof. In some embodiments, the CD14+ monocyte is from a second biological sample comprising PBMCs. [0664] In some embodiments, an isolated population of APCs can be enriched or substantially enriched. In some embodiments, the isolated population of APCs is at least 30%, at least 50%, at least 75%, or at least 90% homogeneous. In some embodiments, the isolated population of APCs is at least 60%, at least 75%, or at least 90% homogeneous. APCs, such as APCs can include, for example, APCs derived in culture from monocytic dendritic precursors as well as endogenously-derived APCs present in tissues such as, for example, peripheral blood, cord blood, skin, spleen, bone marrow, thymus, and lymph nodes. [0665] APCs and cell populations substantially enriched for APCs can be isolated by methods also provided by the present disclosure. The methods generally include obtaining a population of cells that includes APC precursors, differentiation of the APC precursors into immature or mature APCs, and can also include the isolation of APCs from the population of differentiated immature or mature APCs. [0666] APC precursor cells can be obtained by methods known in the art. APC precursors can be isolated, for example, by density gradient separation, fluorescence activated cell sorting (FACS), immunological cell separation techniques such as panning, complement lysis, rosetting, magnetic cell separation techniques, nylon wool separation, and combinations of such methods. Methods for immuno-selecting APCs include, for example, using antibodies to cell surface markers associated with APC precursors, such as anti-CD34 and/or anti-CD14 antibodies coupled to a substrate. [0667] Enriched populations of APC precursors can also be obtained. Methods for obtaining such enriched precursor populations are known in the art. For example, enriched populations of APC precursors can be isolated from a tissue source by selective removal of cells that adhere to a substrate. Using a tissue source such as, e.g., bone marrow or peripheral blood, adherent monocytes can be removed from cell preparations using a commercially-treated plastic substrate (e.g., beads or magnetic beads) to obtain a population enriched for nonadherent APC precursors. [0668] Monocyte APC precursors can also be obtained from a tissue source by using an APC precursor-adhering substrate. For example, peripheral blood leukocytes isolated by, e.g., leukapheresis, are contacted with a monocytic APC precursor-adhering substrate having a high surface area to volume ratio and the adherent monocytic APC precursors are separated. In additional WSGR Docket No.50401-795.601 embodiments, the substrate coupled can be a particulate or fibrous substrate having a high surface-to- volume ratio, such as, for example, microbeads, microcarrier beads, pellets, granules, powder, capillary tubes, microvillous membrane, and the like. Further, the particulate or fibrous substrate can be glass, polystyrene, plastic, glass-coated polystyrene microbeads, and the like. [0669] The APC precursors can also be cultured in vitro for differentiation and/or expansion. Methods for differentiation/expansion of APC precursors are known in the art. Generally, expansion can be achieved by culturing the precursors in the presence of at least one cytokine that induces APC (e.g., dendritic cell) differentiation/proliferation. Typically, these cytokines are granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor (GM-CSF). In addition, other agents can be used to inhibit proliferation and/or maturation of non-APC cell types in the culture, thereby further enriching the population of APC precursors. Typically, such agents include cytokines such as, e.g., IL-13, IL-4, or IL-15, and the like. [0670] The isolated populations of APC precursors are cultured and differentiated to obtain immature or mature APCs. Suitable tissue culture media include, for example, AIM-V®, RPMI 1640, DMEM, X-VIVO, and the like. The tissue culture media is typically supplemented with amino acids, vitamins, divalent cations, and cytokines to promote differentiation of the precursors toward the APC phenotype. Typically, the differentiation-promoting cytokines are GM-CSF and/or IL-4. [0671] Further, cultures of APC precursors during expansion, differentiation, and maturation to the APC phenotype can include plasma to promote the development of APCs. A typical plasma concentration is about 5%. In addition, where, for example, APC precursors are isolated by adherence to a substrate, plasma can be included in the culture media during the adherence step to promote the CD14+ phenotype early in culture. A typical plasma concentration during adherence is about 1% or more. [0672] The monocytic APC precursors can be cultured for any suitable time. In certain embodiments, suitable culture times for the differentiation of precursors to immature APCs can be about 1 to about 10 days, e.g., about 4 to about 7 days. The differentiation of immature APCs from the precursors can be monitored by methods known to those skilled in the art, such as by the presence or absence of cell surface markers (e.g., CD11c+, CD83low, CD86−/low, HLA-DR+). Immature APCs can also be cultured in appropriate tissue culture medium to maintain the immature APCs in a state for further differentiation or antigen uptake, processing and presentation. For example, immature APCs can be maintained in the presence of GM-CSF and IL-4. [0673] In some embodiments, APC precursors can be isolated prior to differentiation. In some embodiments, the isolated population can be enriched or substantially enriched for APC precursors. In some embodiments, APC precursors are isolated with a CD14 specific probe. In one some embodiments, CD14 expressing cells are detected by FACS using a CD14 specific probe either WSGR Docket No.50401-795.601 directly conjugated to a fluorescent molecule (e.g., FITC or PE) or with an unlabeled antibody specific for CD14 and a labeled second antibody specific for the first antibody. CD14+ cells can also be separated from CD14low and CD14− cells by FACS sorting. Gating for CD14high positivity can be determined in reference to CD14 staining on, e.g., PBMC-derived monocytes. Typically, the CD14 specific binding agent is, for example, an anti-CD14 antibody (e.g., monoclonal or antigen binding fragments thereof). A number of anti-CD14 antibodies suitable for use in the present disclosure are well known to the skilled artisan and many can be purchased commercially. Differentiation into immature APCs (CD14 negative) can take place following isolation. [0674] In some embodiments, a CD14 specific probe is coupled to a substrate and the CD14+ cells are isolated by affinity selection. A population of cells that includes CD14+ cells is exposed to the coupled substrate and the CD14+ cells are allowed to specifically adhere. Non-adhering CD14− cells are then washed from the substrate, and the adherent cells are then eluted to obtain an isolated cell population substantially enriched in APC precursors. The CD14 specific probe can be, for example, an anti-CD14 antibody. The substrate can be, for example, commercially available tissue culture plates or beads (e.g., glass or magnetic beads). Methods for affinity isolation of cell populations using substrate-coupled antibodies specific for surface markers are generally known. [0675] During culture, immature APCs can optionally be exposed to a predetermined antigen. Suitable predetermined antigens can include any antigen for which T-cell modulation is desired. Antigens can include, for example, bacterial cells, viruses, partially purified or purified bacterial, viral, fungal, protozoan, or helminth antigens, recombinant cells expressing an antigen on its surface, and any other antigen. Any of the antigens can also be presented as a peptide or recombinantly produced protein or portion thereof. Following contact with antigen, the cells can be cultured for any suitable time to allow antigen uptake and processing, to expand the population of antigen-specific APCs, and the like. [0676] For example, in some embodiments, the immature APCs can be cultured following antigen uptake to promote maturation of the immature APCs into mature APCs that present antigen in the context of MHC molecules. Methods for APC maturation are known. Such maturation can be performed, for example, by culture in the presence of known maturation factors, such as cytokines (e.g., TNF-α, IL-1β, or CD40 ligand), bacterial products (e.g., LPS or BCG), and the like. The maturation of immature APCs to mature APCs can be monitored by methods known in the art, such as, for example by measuring the presence or absence of cell surface markers (e.g., upregulation of CD83, CD86, and MHC molecules) or testing for the expression of mature APC specific mRNA or proteins using, for example, an oligonucleotide array. [0677] Optionally, the immature APCs can be cultured in an appropriate tissue culture medium to expand the cell population and/or maintain the immature APCs in state for further differentiation or WSGR Docket No.50401-795.601 antigen uptake. For example, immature APCs can be maintained and/or expanded in the presence of GM-CSF and IL-4. Also, the immature APCs can be cultured in the presence of anti-inflammatory molecules such as, for example, anti-inflammatory cytokines (e.g., IL-10 and TGF-β) to inhibit immature APC maturation. [0678] In another aspect, the isolated population of APCs is enriched for mature APCs. The isolated population of mature APCs can be obtained by culturing a differentiated population of immature APCs in the presence of maturation factors as described above (e.g., bacterial products, and/or proinflammatory cytokines), thereby inducing maturation. Immature APCs can be isolated by removing CD14+ cells. [0679] According to yet another aspect of the present disclosure, APCs can be preserved, e.g., by cryopreservation either before exposure or following exposure to a suitable antigen. Cryopreservation agents which can be used include dimethyl sulfoxide (DMSO), glycerol, polyvinylpyrrolidone, polyethylene glycol, albumin, dextran, sucrose, ethylene glycol, i-erythritol, D-ribitol, D-mannitol, D- sorbitol, i-inositol, D-lactose, choline chloride, amino acids, methanol, acetamide, glycerol monoacetate, and inorganic salts. A controlled slow cooling rate can be critical. Different cryoprotective agents and different cell types may have different optimal cooling rates. The heat of fusion phase where water turns to ice typically can be minimal. The cooling procedure can be carried out by use of, e.g., a programmable freezing device or a methanol bath procedure. Programmable freezing apparatuses allow determination of optimal cooling rates and facilitate standard reproducible cooling. Programmable controlled-rate freezers such as Cryomed or Planar permit tuning of the freezing regimen to the desired cooling rate curve. [0680] After thorough freezing, APCs can be rapidly transferred to a long-term cryogenic storage vessel. In some embodiments, samples can be cryogenically stored in liquid nitrogen (−196 °C) or its vapor (−165 °C). Considerations and procedures for the manipulation, cryopreservation, and long term storage of hematopoietic stem cells, particularly from bone marrow or peripheral blood, is largely applicable to the APCs of the present disclosure. [0681] Frozen cells are preferably thawed quickly (e.g., in a water bath maintained at 37-41 °C) and chilled immediately upon thawing. It can be desirable to treat the cells in order to prevent cellular clumping upon thawing. To prevent clumping, various procedures can be used, including the addition before and/or after freezing of DNAse, low molecular weight dextran and citrate, hydroxyethyl starch, and the like. The cryoprotective agent, if toxic in humans, can be removed prior to therapeutic use of the thawed APCs. One way in which to remove the cryoprotective agent is by dilution to an insignificant concentration. Once frozen APCs have been thawed and recovered, they can be used to activate T cells as described herein with respect to non-frozen APCs. WSGR Docket No.50401-795.601 [0682] In one aspect, a composition for T cell activation comprises a population of immune cells that has been depleted of one or more types of immune cells. For example, a composition can comprise a population of immune cells that has been depleted of one or more types of immune cells that express one or more proteins, such as one or more cell surface receptors. In some embodiments, a composition comprises a population of immune cells from a biological sample comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, wherein an amount of CD14 and/or CD25 expressing immune cells in the population is proportionally different from an amount of immune cells expressing CD14 and/or CD25 in the biological sample. For example, a composition can comprise a population of immune cells from a biological sample comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, wherein an amount of CD14 expressing immune cells in the population is proportionally different from an amount of immune cells expressing CD14 in the biological sample. For example, a composition can comprise a population of immune cells from a biological sample comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, wherein an amount of CD25 expressing immune cells in the population is proportionally different from an amount of immune cells expressing CD25 in the biological sample. For example, a composition can comprise a population of immune cells from a biological sample comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, wherein an amount of CD14 and CD25 expressing immune cells in the population is proportionally different from an amount of immune cells expressing CD14 and CD25 in the biological sample. For example, a composition can comprise a population of immune cells from a biological sample, wherein an amount of immune cells expressing CD14 and CD25 in the population is proportionally less than an amount of immune cells expressing CD14 and CD25 in the biological sample. [0683] Provided herein is a method of preparing antigen-specific T cells ex vivo, the method comprises (a) depleting CD14+ cells and/or CD25+ cells from a population of immune cells comprising antigen-presenting cells (APCs) and T cells, thereby forming a CD14 and/or CD25 depleted population of immune cells comprising a first population of APCs and T cells, wherein the population of immune cells is from a biological sample from a human subject; (b) incubating the first population of APCs and T cells from (a) for a first time period in the presence of: (i) FMS-like tyrosine kinase 3 receptor ligand (FLT3L), and (ii) (A) a polypeptide comprising an epitope sequence, wherein the epitope sequence is from a protein encoded by the genome of a cancer cell, or (B) a polynucleotide encoding the polypeptide; thereby forming a population of cells comprising stimulated T cells; (c) expanding the stimulated T cells from (b), thereby forming an expanded population of cells comprising antigen-specific T cells, wherein the antigen-specific T cells express a T-cell WSGR Docket No.50401-795.601 receptor (TCR) specific to a peptide:MHC complex comprising: (i) a peptide consisting of the epitope sequence from the protein encoded by the genome of the cancer cell, and (ii) an MHC molecule expressed by the APCs of the population of immune cells of (a). [0684] In some embodiments, the expanded population of cells comprises from at least 5x105 to at least 5x1011 total cells. In some embodiments, the expanded population of cells comprises at least 1x106 total cells. In some embodiments, the expanded population of cells comprises at least 5x106 total cells. In some embodiments, the expanded population of cells comprises at least 1x107 total cells. In some embodiments, the expanded population of cells comprises at least 5x107 total cells. In some embodiments, the expanded population of cells comprises at least 1x108 total cells. In some embodiments, the expanded population of cells comprises at least 5x108 total cells. In some embodiments, the expanded population of cells comprises at least 1x109 total cells. In some embodiments, the expanded population of cells comprises at least 5x109 total cells. In some embodiments, the expanded population of cells comprises at least 1x1010 total cells. In some embodiments, the expanded population of cells comprises at least 5x1010 total cells. In some embodiments, the expanded population of cells comprises at least 1x1011 total cells. In some embodiments, the expanded population of cells comprises at least 5x1011 total cells. In some embodiments, the expanded population of cells comprises from 1x108 to 1x1011 total cells. In some embodiments, the expanded population of cells comprises from 0,75x108 to 1.25x1010 total cells. In some embodiments the expanded population of cells comprises from 5x108 to 1x109 total cells. In some embodiments, the expanded population of cells comprises 5x108 to 1x109 total cells. In some embodiments, the expanded population of cells comprises 5x108 to 2x109 total cells. [0685] In some embodiments, the subject is pretreated with FLT3L at least about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 1 week before isolation of PBMC or leukapheresis. In some embodiments, the subject is pretreated with FLT3L at least about 1 week, 2 weeks, 3 weeks, 4 weeks, or 5 weeks before isolation of PBMC or leukapheresis. [0686] In some embodiments, the cell population is enriched for CD11c+ cells. In some embodiments, the antigen loaded APC comprises dendritic cells (DCs). In some embodiments, the antigen loaded APC comprises plasmacytoid dendritic cells (pDCs). In some embodiments, the antigen loaded APC comprises CD1c+ DCs. In some embodiments, the antigen loaded APC comprises CD141+ DCs. In some embodiments, the cell population comprises macrophages. In some embodiments, the method further comprises reducing or depleting CD19+ cells from the cell population for activating or enriching antigen activated T cells. In some embodiments, the method further comprises reducing or depleting both CD11b+ and CD19+ cells from the cell population for activating or enriching antigen activated T cells. WSGR Docket No.50401-795.601 [0687] In some embodiments, the method further comprises reducing or depleting CD14+ cells from the cell population for preparing and enriching antigen activated T cells. In some embodiments, the method further comprises reducing or depleting CD25+ cells from the cell population for preparing and enriching antigen activated T cells. In some embodiments, the method further comprises reducing or depleting one or more of CD19+, CD14+, CD25+ or CD11b+ cells from the cell population for activating or enriching antigen activated T cells. In some embodiments, depleting comprises depleting CD14+ cells directly from a washed peripheral blood mononuclear cell (PBMC) sample from a human subject. In some embodiments, depleting comprises depleting CD25+ cells directly from a washed peripheral blood mononuclear cell (PBMC) sample from a human subject. In some embodiments, depleting comprises depleting CD14+ cells and CD25+ cells directly from a washed peripheral blood mononuclear cell (PBMC) sample from a human subject. In some embodiments, depleting comprises depleting CD14+ cells directly from a cryopreserved peripheral blood mononuclear cell (PBMC) sample from a human subject. In some embodiments, depleting comprises depleting CD25+ cells directly from a cryopreserved peripheral blood mononuclear cell (PBMC) sample from a human subject. In some embodiments, depleting comprises depleting CD14+ cells and CD25+ cells directly from a cryopreserved peripheral blood mononuclear cell (PBMC) sample from a human subject. In some embodiments, the depleted population of cells is incubated for a first time period in the presence of FLT3L and a polypeptide comprising at least two different epitope sequences. In some embodiments, the depleted population of cells is incubated for a first time period in the presence of FLT3L and a polynucleic acid encoding a polypeptide comprising at least two different epitope sequences. In some embodiments, each of the at least two different epitope sequences is from the same protein encoded by the genome of a cancer cell. In some embodiments, each of the at least two different epitope sequences is from a different protein encoded by the genome of a cancer cell. In some embodiments, the same protein encoded by the genome of a cancer cell is RAS. In some embodiments, a first epitope sequence of the at least two different epitope sequences are connected to a second epitope sequence of the at least 2 different epitope sequences via a linker sequence. In some embodiments, the at least two different epitope sequences are expressed as a single polypeptide chain. In some embodiments, the polypeptide comprises at least 2 to at least 15 or more different epitope sequences from two or more different proteins encoded by the genome of a cancer cell. In some embodiments, the polypeptide comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10 or more different epitope sequences from two or more different proteins encoded by the genome of a cancer cell. [0688] In some embodiments, the method comprises introducing the polynucleotide encoding the polypeptide or the mRNA encoding the polypeptide into the APCs of the first population of APCs and T cells. In some embodiments, introducing comprises electroporating. In some embodiments, WSGR Docket No.50401-795.601 introducing comprises nucleofecting. In some embodiments, introducing is carried out without separating the T cells from the APCs of the first population of APCs and T cells. In some embodiments, the method is performed in less than 35 days. In some embodiments, the method is performed in less than 30 days. In some embodiments, the method is performed in less than 28 days. In some embodiments, the method is performed in less than 25 days. In some embodiments, the method is performed in less than 20 days, in some embodiments. the method is performed in less than 15 days. In some embodiments, the method is performed in less than 10 days. In some embodiments, the method is performed in less than 5 days. In some embodiments, CD8+ antigen-specific T cells are expanded. In some embodiments CD4+ antigen-specific T cells are expanded. In some embodiments, the fraction of CD8+ antigen-specific T cells of the total number of T cells in the expanded population of cells is at least two-fold higher than the fraction of CD8+ antigen-specific T cells of the total number of CD8+ T cells in the CD14 and/or CD25 depleted population of immune cell. In some embodiments, the fraction of CD8+ antigen-specific T cells of the total number of T cells in the expanded population of cells is at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold higher than the fraction of CD8+ antigen-specific T cells of the total number of CD8+ T cells in the CD14 and/or CD25 depleted population of immune cell. In some embodiments, the fraction of CD4+ antigen-specific T cells of the total number of T cells in the expanded population of cells is at least two-fold higher than the fraction of CD4+ antigen-specific T cells of the total number of CD4+ T cells in the CD14 and/or CD25 depleted population of immune cell. In some embodiments, the fraction of CD4+ antigen-specific T cells of the total number of T cells in the expanded population of cells is at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold higher than the fraction of CD4+ antigen-specific T cells of the total number of CD4+ T cells in the CD14 and/or CD25 depleted population of immune cell. In some embodiments, at least 0.1% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 0.5% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 1% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 5% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 10% of the CD8+ T cells in the expanded population of cells are CD8+ antigen- specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 20% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 30% of the CD8+ T cells in the expanded population of cells WSGR Docket No.50401-795.601 are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 40% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 50% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 60% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 70% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 80% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 90% of the CD8+ T cells in the expanded population of cells are CD8+ antigen- specific T cells derived from naïve CD8+ T cells. In some embodiments, at least 0.1% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 0.5% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 1% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 5% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 10% of the CD4+ T cells in the expanded population of cells are CD4+ antigen- specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 20% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 30% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 40% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 50% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 60% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 70% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 80% of the CD4+ T cells in the expanded population of cells are CD4+ antigen-specific T cells derived from naïve CD4+ T cells. In some embodiments, at least 90% of the CD4+ T cells in the expanded population of cells are CD4+ antigen- specific T cells derived from naïve CD4+ T cells. [0689] In some embodiments, the expanding comprises contacting the population of cells comprising stimulated T cells with a second population of mature APCs. In some embodiments, the second population of mature APCs have been incubated with FLT3L. In some embodiments, the second WSGR Docket No.50401-795.601 population of mature APCs have been incubated with FLT3L for at least 1 day prior to contacting the population of cells comprising stimulated T cells with the second population of mature APCs. In some embodiments, the second population of mature APCs have been incubated with FLT3L for 2 days. In some embodiments, the second population of mature APCs have been incubated with FLT3L for 3 days. In some embodiments, the second population of mature APCs have been incubated with FLT3L for 4 days. In some embodiments, the second population of mature APCs have been incubated with FLT3L for 5 days. In some embodiments, the second population of mature APCs present the peptide consisting of the epitope sequence from the protein encoded by the genome of the cancer cells. In some embodiments, the second population of mature APCs have been incubated with FLT3L and present the peptide consisting of the epitope sequence from the protein encoded by the genome of the cancer cell. In some embodiments, expanding comprises expanding the population of cells comprising stimulated T cells for a second time period, thereby forming an expanded population of T cells. In some embodiments, depleting CD14+ cells from the population of immune cells comprising a first population of APCs and T cells comprises contacting the population of immune cells comprising a first population of APCs and T cells with a CD14 binding agent. In some embodiments, depleting CD25+ cells from the population of immune cells comprising a first population of APCs and T cells comprises contacting the population of immune cells comprising a first population of APCs and T cells with a CD25 binding agent. In some embodiments, depleting CD14+ cells and/or CD25+ cells from the population of immune cells comprising a first population of APCs and T cells comprises contacting the population of immune cells comprising a first population of APCs and T cells with a CD14 binding agent and/or a CD25 binding agent. [0690] In some embodiments the stimulant for activating the cells comprises FL3TL. [0691] In some embodiments the agent promoting cell growth and maintenance ex vivo comprises a growth factor, a cytokine, an amino acid, a supplement or a combination thereof. [0692] In some embodiments the antigen loaded APCs can stimulate T cells for 2, 3, 4, 5, 6, or 7 days. [0693] In some embodiments, the antigenic peptides used to prepare antigen loaded APCs are long peptides comprising at least 20 amino acids, or at least 30 amino acids or at least 40 amino acids or at least 50 amino acids, or any number of amino acids in between. In some embodiments, the antigenic peptides used to prepare antigen loaded APCs comprise the amino acids flanking on either side of the epitope that facilitate endogenous processing of the antigenic peptide for increased rate of presentation to a T cell. [0694] A longer immunogenic peptide can be designed in several ways. In some embodiments, when HLA-binding peptides are predicted or known, a longer immunogenic peptide could consist of (1) individual binding peptides with extensions of 2-5 amino acids toward the N- and C-terminus of each WSGR Docket No.50401-795.601 corresponding gene product; or (2) a concatenation of some or all of the binding peptides with extended sequences for each. In other embodiments, when sequencing reveals a long (>10 residues) epitope sequence, e.g., an epitope derived from a protein encoded by a gene in a cancer cell (e.g., due to a frameshift, read-through or intron inclusion that leads to a novel peptide sequence), a longer antigen peptide could consist of the entire stretch of novel antigen-specific amino acids as either a single longer peptide or several overlapping longer peptides. In some embodiments, use of a longer peptide is presumed to allow for endogenous processing by patient cells and can lead to more effective antigen presentation and induction of T cell responses. In some embodiments, two or more peptides can be used, where the peptides overlap and are tiled over the long antigen peptide. [0695] In some embodiments, each of the plurality of antigenic peptide comprises the same antigenic epitope. In some embodiments the plurality of antigenic peptide comprises more than one antigenic epitope. [0696] In some embodiments the one or more polynucleotides encoding the plurality of antigen peptides is DNA. [0697] In some embodiments the one or more polynucleotides encoding the plurality of antigen peptides is inserted in one or more mammalian expression vectors. [0698] In some embodiments the one or more polynucleotides encoding the plurality of antigen peptides is messenger RNA. [0699] In some embodiments, the present disclosure provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising a modified nucleoside. [0700] In some embodiments, the present disclosure provides gene therapy vectors comprising the RNA, oligoribonucleotide, and polyribonucleotide. [0701] In some embodiments, the present disclosure provides gene therapy methods and gene transcription silencing methods comprising same. [0702] In some embodiments, the polynucleotide encodes a single antigenic peptide. [0703] In some embodiments, the one polynucleotide encodes more than one antigenic peptide. [0704] In some embodiments, the polynucleotide is messenger RNA. In some embodiments, each messenger RNA comprises coding sequence for two or more antigenic peptides in tandem. [0705] In some embodiments each messenger RNA comprises a coding sequence for two, three, four, five, six, seven, eight, nine or ten or more antigenic peptides in tandem. Typically, an mRNA comprises a 5'-UTR, a protein coding region, and a 3'-UTR. mRNA only possesses limited half-life in cells and in vitro. In some embodiments, the mRNA is self-amplifying mRNA. In the context of the present disclosure, mRNA can be generated by in vitro transcription from a DNA template. The in vitro transcription methodology is known to the skilled person. For example, there is a variety of in vitro transcription kits commercially available. WSGR Docket No.50401-795.601 [0706] The stability and translation efficiency of RNA can be modified. For example, RNA can be stabilized, and its translation increased by one or more modifications having a stabilizing effect and/or increasing translation efficiency of RNA. Such modifications are described, for example, in PCT/EP2006/009448 incorporated herein by reference. In order to increase expression of the RNA used according to the present disclosure, it can be modified within the coding region, i.e., the sequence encoding the expressed peptide or protein, without altering the sequence of the expressed peptide or protein, so as to increase the GC-content to increase mRNA stability and to perform a codon optimization and, thus, enhance translation in cells. [0707] In some embodiments, an mRNA can include multiple antigenic epitopes. In some a mRNA of a large portion of, or even the entire coding region of a gene comprising sequences encoding antigenic peptides are delivered into an immune cell for endogenous processing and presentation of antigens. [0708] In some embodiments, the coding sequence for each antigenic peptide is 24-120 nucleotides long. [0709] In some embodiments, the mRNA is 50-10,000 nucleotides long. In some embodiments, the mRNA is 100- 10,000 nucleotides long. In some embodiments, the mRNA is 200-10,000 nucleotides long. In some embodiments, the mRNA is 50-5,000 nucleotides long. In some embodiments, the mRNA is 100-5,000 nucleotides long. In some embodiments, the mRNA is 100-1,000 nucleotides long. In some embodiments, the mRNA is 300-800 nucleotides long. In some embodiments, the mRNA is 400-700 nucleotides long. In some embodiments, the mRNA is 450-600 nucleotides long. In some embodiments, the mRNA is at least 200 nucleotides long. In some embodiments the mRNA is greater than 250 nucleotides, greater than 300 nucleotides, greater than 350 nucleotides, greater than 400 nucleotides, greater than 450 nucleotides, greater than 500 nucleotides, greater than 550 nucleotides, greater than 600 nucleotides, greater than 650 nucleotides, greater than 700 nucleotides, greater than 750 nucleotides, greater than 800 nucleotides, greater than 850 nucleotides long, greater than 900 nucleotides long greater than 950 nucleotides long, greater than 1000 nucleotides long, greater than 2000 nucleotides long, greater than 3000 nucleotides long, greater than 4000 nucleotides long or greater than 5000 nucleotides long. [0710] In some embodiments, mRNA encoding one or more antigenic peptide is modified, wherein the modification relates to the 5’-UTR. In some embodiments, the modification relates to providing an RNA with a 5'-cap or 5’- cap analog in the 5’-UTR. The term “5'-cap” refers to a cap structure found on the 5'-end of an mRNA molecule and generally consists of a guanosine nucleotide connected to the mRNA via an unusual 5' to 3' triphosphate linkage. In some embodiments, this guanosine is methylated at the 7-position. The term “conventional 5'-cap” refers to a naturally occurring RNA 5'- cap, to the 7-methylguanosine cap (m G). In the context of the present disclosure, the term “5'-cap” WSGR Docket No.50401-795.601 includes a 5'-cap analog that resembles the RNA cap structure and is modified to possess the ability to stabilize RNA and/or enhance translation of RNA if attached thereto, in vivo and/or in a cell. In some embodiments, mRNA is capped co-transcriptionally. [0711] In some embodiments, the mRNA encoding one or more antigenic peptides comprise a 3’- UTR comprising a poly A tail. In some embodiments, the poly A tail is 100-200 bp long. In some embodiments, the poly A tail is longer than 20 nucleotides. In some embodiments, the poly A tail is longer than 50 nucleotides. In some embodiments, the poly A tail is longer than 60 nucleotides. In some embodiments, the poly A tail is longer than 70 nucleotides. In some embodiments, the poly A tail is longer than 80 nucleotides. In some embodiments, the poly A tail is longer than 90 nucleotides. In some embodiments, the poly A tail is longer than 100 nucleotides. In some embodiments, the poly A tail is longer than 110 nucleotides. In some embodiments, the poly A tail is longer than 120 nucleotides. In some embodiments, the poly A tail is longer than 130 nucleotides. In some embodiments, the poly A tail is longer than 140 nucleotides. In some embodiments, the poly A tail is longer than 150 nucleotides. In some embodiments, the poly A tail is longer than 160 nucleotides. In some embodiments, the poly A tail is longer than 170 nucleotides. In some embodiments, the poly A tail is longer than 180 nucleotides. In some embodiments, the poly A tail is longer than 190 nucleotides. In some embodiments, the poly A tail is longer than 200 nucleotides. In some embodiments, the poly A tail is longer than 210 nucleotides. In some embodiments, the poly A tail is longer than 220 nucleotides. In some embodiments, the poly A tail is longer than 230 nucleotides. In some embodiments, the poly A tail is longer than 100 nucleotides. In some embodiments, the poly A tail is longer than 240 nucleotides. In some embodiments, the poly A tail is longer than 100 nucleotides. In some embodiments, the poly A tail is about 250 nucleotides. [0712] In some embodiments, the poly A tail comprises 100-250 adenosine units. In some embodiments, the poly A tail comprises 120-130 adenine units. In some embodiments, the poly A tail comprises 120 adenine units. In some embodiments, the poly A tail comprises 121 adenine units. In some embodiments, the poly A tail comprises 122 adenine units. In some embodiments, the poly A tail comprises 123 adenine units. In some embodiments, the poly A tail comprises 124 adenine units. In some embodiments, the poly A tail comprises 125 adenine units. In some embodiments, the poly A tail as 129 bases. [0713] In some embodiments, the coding sequence for two consecutive antigenic peptides are separated by a spacer or linker. [0714] In some embodiments, the spacer or linker comprises up to 5000 nucleotide residues. An exemplary spacer sequence is GGCGGCAGCGGCGGCGGCGGCAGCGGCGGC. Another exemplary spacer sequence is GGCGGCAGCCTGGGCGGCGGCGGCAGCGGC. Another exemplary spacer sequence is GGCGTCGGCACC. Another exemplary spacer sequence is WSGR Docket No.50401-795.601 CAGCTGGGCCTG. Another exemplary spacer is a sequence that encodes a lysine, such as AAA or AAG. Another exemplary spacer sequence is CAACTGGGATTG. [0715] In some embodiments, the mRNA comprises one or more additional structures to enhance antigen epitope processing and presentation by APCs. [0716] In some embodiments, the linker or spacer region can contain cleavage sites. The cleavage sites ensure cleavage of the protein product comprising strings of epitope sequences into separate epitope sequences for presentation. The preferred cleavage sites are placed adjacent to certain epitopes in order to avoid inadvertent cleavage of the epitopes within the sequences. In some embodiments, the design of epitopes and cleavage regions on the mRNA encoding strings of epitopes are non-random. [0717] In certain embodiments, an mRNA encoding an antigen peptide of the present disclosure is administered to a subject in need thereof. In some embodiments, the mRNA to be administered comprises at least one modified nucleoside-phosphate. [0718] In some embodiments, T cells are activated with antigenic peptides by artificial antigen- presenting cells. In some embodiments, artificial scaffolds are used to activate a T cell with antigenic peptides, the artificial scaffolds are loaded with antigenic peptides couples with an MHC antigen to which the antigenic peptide can bind with high affinity. [0719] In some embodiments, the additional structures comprise encoding specific domains from the proteins selected from a group MITD, SP1, and 10th Fibronectin Domain: 10FnIII. [0720] In some embodiments, the cells derived from peripheral blood or from leukapheresis are contacted with the plurality of antigen peptides, or one or more polynucleotides encoding the plurality of antigen peptides once or more than once to prepare the antigen loaded APCs. [0721] In some embodiments, the method comprises incubating the APC or one or more of the APC preparations with a first medium comprising at least one cytokine or growth factor for a first time period. [0722] In some embodiments, the method comprises incubating one or more of the APC preparations with at least one peptide for a second time period. [0723] In some embodiments, the enriched cells further comprise CD1c+ cells. [0724] In some embodiments, the cell population is enriched for CD11c+ and CD141+ cells. [0725] In some embodiments, the cell population comprising the antigen loaded APCs comprises greater than 1%, 2%, 3%, 4%, 5%, 6,7%, 8%, 9%, 10%, 15%, 20%, 25%, 30% 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% or more CD11c+ cells. [0726] In some embodiments, the cell population comprising the antigen loaded APCs comprises less than 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 20%, 10%, 8%, 7%, 6%, 5%, 4% or lower CD11b+ expressing cells. WSGR Docket No.50401-795.601 [0727] In some embodiments, the cell population comprising the antigen loaded APCs comprises greater than 1%, 2%, 3%, 4%, 5%, 6,7%, 8%, 9%, 10%, 15%, 20%, 25%, 30% 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% antigenic peptide expressing cells that are CD11c+. [0728] In some embodiments, the cell population comprising the antigen loaded APCs comprises greater than 1%, 2%, 3%, 4%, 5%, 6,7%, 8%, 9%, 10%, 15%, 20%, 25%, 30% 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% antigenic peptide expressing cells that are CD11c+ CD1c+, or CD141+ cells. [0729] In some embodiments, the antigen loaded APCs comprise mature APCs. [0730] In some embodiments, the method comprises obtaining a biological sample from a subject comprising at least one APC and at least one PBMC or at least on T cell. [0731] In some embodiments, the method comprises depleting cells expressing CD14 and/or CD25 and/or CD19 from a biological sample, thereby obtaining a CD14 and/or CD25 and/or CD19 cell depleted sample. [0732] In some embodiments, the method comprises incubating a CD14 and/or CD25 and/or CD19 cell depleted sample with FLT3L for a first time period. [0733] In some embodiments, the method comprises incubating at least one peptide with a CD14 and/or CD25 and/or CD19 cell depleted sample for a second time period, thereby obtaining a first matured APC peptide loaded sample. [0734] Preparing antigen activated T cells using antigen loaded APCs. [0735] The NEO-STIM process can comprise methods of preparing antigen activated (e.g., RAS activated) T cells using antigen loaded APCs. [0736] In some embodiments, the antigen loaded APC (APC) prepared by the methods described above is incubated with T cells to obtain antigen activated T cells. The method can comprise generating at least one antigen specific T cell where the antigen is an antigen derived from a cancer cell. In some embodiments, the generating at least one antigen specific T cell comprises generating a plurality of antigen specific T cells. [0737] In some embodiments, the T cells are obtained from a biological sample from a subject. [0738] In some embodiments, the T cells are obtained from a biological sample from the same subject from whom the APCs are derived. In some embodiments, the T cells are obtained from a biological sample from a different subject than the subject from whom the APCs are derived. [0739] In some embodiments, the APCs and/or T cells are derived from a biological sample which is peripheral blood mononuclear cells (PBMC). In some embodiments, the APCs and/or T cells are derived from a biological sample which is a leukapheresis sample. [0740] In some embodiments, the APC comprises a dendritic cell (DC). WSGR Docket No.50401-795.601 [0741] In some embodiments, the APC is derived from a CD14+ monocyte, or is a CD14 enriched APC, or is a CD141 enriched APC. [0742] In some embodiments, the CD14+ monocyte is enriched from a biological sample from a subject comprising peripheral blood mononuclear cells (PBMCs). [0743] In some embodiments, the APC is PBMC. In some embodiments, the PBMC is freshly isolated PBMC. In some embodiments the PBMC is frozen PBMC. In some embodiments, the PBMC is autologous PBMC isolated from the subject or the patient. [0744] In some embodiments, the PBMC is loaded with antigens, where the antigens can be peptides or polypeptides or polynucleotides, such as mRNA, that encode the peptides and polypeptides. PBMCs (monocytes, DCs phagocytic cells) can take up antigens by phagocytosis and process and present them on the surface for T cell activation. Peptides or polypeptides loaded on the PBMCs can be supplemented with adjuvants to increase immunogenicity. In some embodiments, the PBMC is loaded with nucleic acid antigens. Nucleic acid antigens can be in the form of mRNA, comprising sequences encoding one or more antigens. In some embodiments, mRNA antigen loading does not require adjuvant supplementation, because, for example, RNA can act as a self-adjuvant. [0745] In some embodiments, PBMCs are directly isolated or thawed from a frozen sample, and subjected to incubating with one or more antigens. In some embodiments, the PBMC sample is not further cultured for differentiation or subjected to further maturation of one or more cell components within the PBMC, (for example, maturation of antigen-presenting cells, or differentiation of monocytes to dendritic cells), before exposing the PBMCs to one or more antigens or nucleic acid encoding the one or more antigens. In some embodiments one or more cell types are depleted or removed from the freshly isolated PBMC cell population or a freshly thawed PBMC population before exposing or incubating the cells to one or more antigens or nucleic acid encoding the one or more antigens. In some embodiments, CD14+ cells are depleted from the PBMC. In some embodiments, CD25+ cells are depleted from the PBMC. In some embodiments, CD11b+ cells are depleted from the PBMC. In some embodiments, the CD14+ and CD25+ cells are depleted from the PBMCs, before incubating with one or more antigens or one or more nucleic acids encoding the one or more antigens. In some embodiments, the CD11b+, and/or the CD14+ and/or CD25+ cells are depleted from the PBMC. In some embodiments, a method provided herein comprises preparing antigen-specific T cells by depleting CD14+ cells and/or CD25+ cells from a PBMC sample from a human subject containing about the same percentage of immature dendritic cells (DCs) as the percentage of immature DCs in the peripheral blood of the human subject. In some embodiments, a method provided herein comprises preparing antigen-specific T cells by depleting CD14+ cells and/or CD25+ cells from a PBMC sample from a human subject containing about the same percentage of mature DCs as the percentage of mature DCs in the peripheral blood of the human subject. In some WSGR Docket No.50401-795.601 embodiments, a method provided herein comprises preparing antigen-specific T cells by depleting CD14+ cells and/or CD25+ cells from a PBMC sample from a human subject containing about the same ratio of immature DCs to mature DCs as the ratio of immature DCs to mature DCs in the peripheral blood of the human subject. In some embodiments, a method provided herein comprises preparing antigen-specific T cells by depleting CD14+ cells and/or CD25+ cells from a PBMC sample from a human subject that has not been subject to a step of maturing immature DCs into mature DCs. In some cases, the antigen is from a cancer cell. [0746] In some embodiments, the CD14+ monocyte is stimulated with one or more cytokines or growth factors. [0747] In some embodiments, one or more cytokines or growth factors comprise GM-CSF, IL-4, FLT3L, TNF-α, IL-1β, PGE1, IL-6, IL-7, IL-15, IFN-γ, IFN-α, R848, LPS, ss-rna40, poly I:C, or a combination thereof. [0748] In some embodiments, the CD14+ monocyte is from a second biological sample comprising PBMCs. [0749] In some embodiments, the second biological sample is from the same subject. [0750] In some embodiments, the biological sample comprises peripheral blood mononuclear cells (PBMCs). [0751] In some embodiments, the at least one antigen-specific T cell is stimulated in a medium comprising IL-7, IL-15, an indoleamine 2,3-dioxygenase-1 (IDO) inhibitor, an anti-PD-1 antibody, IL-12, or a combination thereof. [0752] In some embodiments, the IDO inhibitor is epacadostat, navoximod, 1-methyltryptophan, or a combination thereof. [0753] In some embodiments, the subject is administered FLT3L prior to obtaining the biological sample for preparing the APCs and/or T cells. [0754] In some embodiments, the T cells are obtained from a biological sample from a subject as described in the previous sections of this disclosure. [0755] In some embodiments, the biological sample is freshly obtained from a subject or is a frozen sample. [0756] In some embodiments, the incubating is in presence of at least one cytokine or growth factor, which comprises GM-CSF, IL-4, FLT3L, TNF-α, IL-1β, PGE1, IL-6, IL-7, IL-15, IFN-γ, IFN-α, IL- 15, R848, LPS, ss-rna40, poly I:C, or any combination thereof. [0757] In some embodiments, a method comprises stimulating T cells with IL-7, IL-15, or a combination thereof. In some embodiments, a method comprises stimulating T cells with IL-7, IL-15, or a combination thereof, in the presence of an IDO inhibitor, a PD-1 antibody or IL-12. In some embodiments, the stimulated T cell is expanded in presence of the one or more antigen epitope WSGR Docket No.50401-795.601 sequence or APCs loaded with the one or more antigen or epitope sequence, or APCs loaded with (e.g. expressing) nucleic acid sequences (such as mRNA sequences) encoding the one or more antigen epitope sequence, one or more cytokines or growth factors comprise GM-CSF, IL-4, FLT3L, TNF-α, IL-1β, PGE1, IL-6, IL-7, IL-15, IFN-γ, IFN-α, R848, LPS, ss-rna40, poly I:C, or a combination thereof, FLT3L, under suitable T cell growth conditions ex vivo. In some embodiments, the method further comprises administering the antigen specific T cells to a subject. [0758] In some embodiments, the method comprises incubating the APC prepared as described in the previous sections with T cells in presence of a medium comprising the at least one cytokines or growth factor to generate antigen activated T cells. [0759] In some embodiments, the incubating comprises incubating a first APC preparation of the APC preparations to the T cells for more than 7 days. In some embodiments, the incubated T cells are stimulated T cells that expand in vitro on presence of the APC preparation, cytokines and growth factors for more than 7 days. [0760] In some embodiments, the incubating comprises incubating a first APC preparation of the APC preparations to the T cells for more than 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 days. [0761] In some embodiments, the first time period of the one or more time periods is about 1, 23, 4, 5, 6, 7, 8, or 9 days. [0762] In some embodiments, a total time period of the separate time periods is less than 28 days. In some embodiments, a total time period of the separate time periods is from 20-27 days. In some embodiments, a total time period of the separate time periods is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, or 39 days. [0763] In some embodiments, a method comprises incubating a first APC preparation of the APC preparations with the T cells for more than 7 days. In some embodiments, a method comprises incubating a first APC preparation of the APC preparations with the T cells for more than 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 days. In some embodiments, a method comprises incubating a first APC preparation of the APC preparations with the T cells for from 7-20, 8-20, 9-20, 10-20, 11- 20, or 12-20 days. In some embodiments, a method comprises incubating a first APC preparation of the APC preparations with the T cells for about 10-15 days. [0764] In some embodiments, a method comprises incubating a second APC preparation of the APC preparations to the T cells for 5-9 days. In some embodiments, a method comprises incubating a second APC preparation of the APC preparations to the T cells for 5, 6, 7, 8, or 9 days. In some embodiments, the method further comprises removing the one or more cytokines or growth factors of the second medium after the third time period and before a start of the fourth time period. WSGR Docket No.50401-795.601 [0765] In some embodiments, a method comprises incubating a third APC preparation of the APC preparations to the T cells for 5-9 days. In some embodiments, the method comprises incubating a third APC preparation of the APC preparations to the T cells for 5, 6, 7, 8, or 9 days. [0766] In some embodiments, the method comprises incubating a first APC preparation of the APC preparations with the T cells for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 days, incubating a second APC preparation of the APC preparations to the T cells for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 days, and incubating a third APC preparation of the APC preparations to the T cells for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 days. [0767] In some embodiments, the method is performed ex vivo. In some embodiments, the T cells are cultured in a medium containing a cytokine. In some embodiments, an example of cytokines includes IL-7. In some embodiments, an example of cytokines includes IL-15. In some embodiments, an example of cytokines includes IL-7 and IL-15. In some embodiments, the T cells are cultured in a medium comprising IL-7, and/or IL-15. In some embodiments, the cytokine in a T cell culture or a medium has a final concentration of at least 0.05 ng/mL, 0.1 ng/mL, 0.2 ng/mL, 0.3 ng/mL, 0.4 ng/mL, 0.5 ng/mL, 0.8 ng/mL, 1 ng/mL, 2 ng/mL, 3 ng/mL, 4 ng/mL, 5 ng/mL, 6 ng/mL, 7 ng/mL, 8 ng/mL, 9 ng/mL, 10 ng/mL, 12 ng/mL, 15 ng/mL, 18 ng/mL, or 20 ng/mL. In some embodiments, the IL-7 in a T cell culture or a medium has a final concentration of at least 0.05 ng/mL, 0.1 ng/mL, 0.2 ng/mL, 0.3 ng/mL, 0.4 ng/mL, 0.5 ng/mL, 0.8 ng/mL, 1 ng/mL, 2 ng/mL, 3 ng/mL, 4 ng/mL, 5 ng/mL, 6 ng/mL, 7 ng/mL, 8 ng/mL, 9 ng/mL, 10 ng/mL, 12 ng/mL, 15 ng/mL, 18 ng/mL, or 20 ng/mL. In some embodiments, the IL-15 in a T cell culture or a medium has a final concentration of at least 0.05 ng/mL, 0.1 ng/mL, 0.2 ng/mL, 0.3 ng/mL, 0.4 ng/mL, 0.5 ng/mL, 0.8 ng/mL, 1 ng/mL, 2 ng/mL, 3 ng/mL, 4 ng/mL, 5 ng/mL, 6 ng/mL, 7 ng/mL, 8 ng/mL, 9 ng/mL, 10 ng/mL, 12 ng/mL, 15 ng/mL, 18 ng/mL, or 20 ng/mL. In some embodiments, the T cells are cultured in a medium further containing FLT3L. In some embodiments, the FLT3L in a T cell culture or a medium has a final concentration of in a T cell culture or a medium has a final concentration of at least 1 ng/mL, 2 ng/mL, 3 ng/mL, 4 ng/mL, 5 ng/mL, 6 ng/mL, 7 ng/mL, 8 ng/mL, 9 ng/mL, 10 ng/mL, 12 ng/mL, 15 ng/mL, 18 ng/mL, 20 ng/mL, 30 ng/mL, 40 ng/mL, 50 ng/mL, 60 ng/mL, 70 ng/mL, 80 ng/mL, 90 ng/mL, 100 ng/mL, or 200 ng/mL. In some embodiments, the T cells are incubated, induced, or stimulated in a medium containing FLT3L for a first period time. In some embodiments, the T cells are incubated, induced, or stimulated in a medium containing additionally added FLT3L for a second period time. In some embodiments, the T cells are incubated, induced, or stimulated in a medium containing additional added FLT3L for a third period time. In some embodiments, the T cells are incubated, induced, or stimulated in a medium containing additional added FLT3L for a fourth, a fifth, or a sixth period time, with freshly added FLT3L in each time period. WSGR Docket No.50401-795.601 [0768] In some embodiments, the T cells are cultured in presence of an antigen, e.g., an antigen presented by an APC, wherein the media comprises high potassium [K]+ content. In some embodiments, the T cells are cultured in presence of high [K]+ content in the media for at least a period of time during the incubation with APCs or T cells. In some embodiments, the [K]+ content in the media is altered for at least a period of time during the incubation with APCs or T cells. In some embodiments, the content in the media is kept constant over the period of T cell ex vivo culture. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 5 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 6 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 7 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 8 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 9 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 10 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 11 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 12 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 13 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 14 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 15 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 16 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 17 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 18 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 19 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 20 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 22 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 25 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 30 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 35 mM. In some embodiments, the [K]+ content in the T cell culture medium is ≥ 40 mM. In some embodiments, the [K]+ content in the T cell culture medium is about 40 mM. [0769] In some embodiments, the [K]+ content in the T cell culture medium is about 40 mM for at least a period of time during the incubation of T cells with antigen. In some embodiments, the antigen can be presented by the antigen loaded APCs. In some embodiments, the T cells in the presence of [K]+ are tested for T effector functions, CD8+ cytotoxicity, cytokine production, and for memory phenotype. In some embodiments, T cells are grown in the presence of high [K]+ express effector T cell phenotype. In some embodiments, T cells grown in presence of high [K]+ express memory cell marker. In some embodiments, T cells grown in presence of high [K]+ do not express T cell exhaustion markers. [0770] In some embodiments, the stimulated T cell is a population of immune cells comprising the activated T cells stimulated with APCs comprising an antigenic peptide-MHC complex. In some WSGR Docket No.50401-795.601 embodiments, a method can comprise incubating a population of immune cells from a biological sample with APCs comprising a peptide-MHC complex, thereby obtaining a stimulated immune cell sample; determining expression of one or more cell markers of at least one immune cell of the stimulated immune cell sample; and determining binding of the at least one immune cell of the stimulated immune cell sample to a peptide-MHC complex; wherein determining expression of certain cell surface markers or other determinant markers, such as intracellular factors, or released agents, such as cytokines etc., and determining binding to the antigen-MHC complex are performed simultaneously. In some embodiments, the one or more cell markers comprise TNF-α, IFN-γ, LAMP- 1, 4-1BB, IL-2, IL-17A, Granzyme B, PD-1, CD25, CD69, TIM3, LAG3, CTLA-4, CD62L, CD45RA, CD45RO, FoxP3, or any combination thereof. In some embodiments, the one or more cell markers comprise a cytokine. In some embodiments, the one or more cell markers comprise a degranulation marker. In some embodiments, the one or more cell markers comprise a cell-surface marker. In some embodiments, the one or more cell markers comprise a protein. In some embodiments, determining binding of the at least one immune cell of the stimulated immune cell sample to the peptide-MHC complex comprises determining binding of the at least one immune cell of the stimulated immune cell sample to an MHC tetramer comprising the peptide and the MHC of the peptide-MHC complex. In some embodiments, the MHC is a class I MHC or a class II MHC. In some embodiments, the peptide-MHC complex comprises one or more labels. [0771] In some embodiments, activation of T cell is verified by detecting the release of a cytokine by the activated T cell. In some embodiments, the cytokine is one or more of: TNF-α, IFN-γ, IL-2, or IL- 18. In some embodiments the activation of T cell is verified by its specific antigen binding and cytokine release. In some embodiments, the activation of T cells is verified by its ability to kill infected cells in vitro. A sample of activated T cells can be used to verify the activation status of the T cells. In some embodiments, a sample from the T cells is withdrawn from the T cell culture to determine the cellular composition and activation state by flow cytometry. [0772] In some embodiments, a percentage of the at least one antigen specific T cell in the composition is at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of total T cells or total immune cells. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 5%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 7%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 10%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 12%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 15%. In some embodiments, the percentage of the at least one antigen WSGR Docket No.50401-795.601 specific T cell in the composition is about 20%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 25%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 30%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 40%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 50%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 60%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 70%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 80%. In some embodiments, the percentage of the at least one antigen specific T cell in the composition is about 90%. [0773] In some embodiments, a percentage of at least one antigen specific CD8+ T cell in the composition is at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 5%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 7%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 10%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 12%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 15%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 20%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 25%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 30%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 40%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 50%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 60%. In some embodiments, the percentage of the at least one antigen specific CD8+ T cells in the composition is about 70% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells. [0774] In some embodiments, at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the CD8+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD8+ T cells. In some embodiments, at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, WSGR Docket No.50401-795.601 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the CD4+ T cells in the expanded population of cells are CD8+ antigen-specific T cells derived from naïve CD4+ T cells. [0775] In some embodiments, a percentage of the at least one antigen specific T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells. [0776] In some embodiments, a percentage of at least one antigen specific CD8+ T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells. [0777] In some embodiments, a percentage of at least one antigen specific CD4+ T cell in the biological sample is at most about 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or 0.5% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells. [0778] In some embodiments, the antigen is an overexpressed antigen, a viral antigen, a bacterial antigen, a protozoan antigen, a helminth antigen, or a combination thereof. [0779] In some embodiments, the number of at least one antigen specific CD8+ T cell in the composition is at least about 1x10^6, 2x10^6, 5x10^6, 1x10^7, 2x10^7, 5x10^7, 1x10^8, 2x10^8, or 5x10^8, antigen specific CD8+ T cells. [0780] In some embodiments, a number of at least one antigen specific CD4+ T cell in the composition is at least about 1x10^6, 2x10^6, 5x10^6, 1x10^7, 2x10^7, 5x10^7, 1x10^8, 2x10^8, or 5x10^8, antigen specific CD4+ T cells. [0781] Method of T cell Manufacturing [0782] Provided herein are methods for antigen specific T cell manufacturing. Provided herein are methods of preparing T cell compositions, such as therapeutic T cell compositions. For example, a method can comprise expanding or inducing antigen specific T cells. Preparing (e.g., inducing or expanding) T cells can also refer to manufacturing T cells, and broadly encompasses procedures to isolate, stimulate, culture, induce, and/or expand any type of T cells (e.g., CD4+ T cells and CD8+ T cells). In one aspect, provided herein is a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating an APC with a population of immune cells from a biological sample depleted of cells expressing CD14 and/or CD25. In some embodiments, the method comprises preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating an APC with a population of immune cells from a biological sample depleted of cells expressing CD11b and/or CD19. In some embodiments, the WSGR Docket No.50401-795.601 method comprises incubating an APC with a population of immune cells from a biological sample depleted of cells expressing any CD11b and/or CD19 and/or CD14 and/or CD25 or any combination thereof. [0783] In a second aspect, provided here is a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating an FMS-like tyrosine kinase 3 receptor ligand (FLT3L)-stimulated APC with a population of immune cells from a biological sample. [0784] In a third aspect, provided herein is a method of preparing a pharmaceutical composition comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising: incubating FMS-like tyrosine kinase 3 receptor ligand (FLT3L) with a population of immune cells from a biological sample for a first time period; and thereafter incubating at least one T cell of the biological sample with an APC. [0785] In a fourth aspect, provided herein is a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods of less than 28 days from incubating the population of immune cells with a first APC preparation of the one or more APC preparations, wherein at least one antigen specific memory T cell is expanded, or at least one antigen specific naïve T cell is induced. [0786] In a fifth aspect, provided herein is a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating a population of immune cells from a biological sample with 3 or less APC preparations for 3 or less separate time periods, wherein at least one antigen specific memory T cell is expanded or at least one antigen specific naïve T cell is induced. [0787] In some embodiments, a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods, thereby stimulating T cells to become antigen specific T cells, wherein a percentage of antigen specific T cells is at least about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells. In some embodiments, a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with 3 or less APC preparations for 3 or less WSGR Docket No.50401-795.601 separate time periods, thereby stimulating T cells to become antigen specific T cells. In some embodiments, a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with 2 or less APC preparations for 2 or less separate time periods, thereby stimulating T cells to become antigen specific T cells. [0788] In some embodiments, provided herein is a method that comprises incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods, thereby stimulating T cells to become antigen specific T cells, wherein the APC preparation is a PBMC cell population from which cells expressing one or more cell surface markers are depleted prior to antigen loading of the APC population. In some embodiments, CD14+ cells are depleted prior to antigen loading of an APC population. In some embodiments, CD25+ cells are depleted prior to antigen loading of an APC population. In some embodiments, CD11b+ cells are depleted prior to antigen loading of an APC population. In some embodiments, CD19+ cells are depleted prior to antigen loading of an APC population. In some embodiments, CD3+ cells are depleted prior to antigen loading of an APC population. In some embodiments, CD25+ cells and CD14+ cells are depleted prior to antigen loading of an APC population. In some embodiments, CD11b+ and CD25+ cells are depleted prior to antigen loading of an APC population. In some embodiments, CD11b+ and CD14+ cells are depleted prior to antigen loading of an APC population. In some embodiments, CD11b+, CD14+ and CD25+ cells are depleted prior to antigen loading of an APC population. In some embodiments, CD11b+, and CD19+ cells are depleted prior to antigen loading of an APC population. In some embodiments, CD11b+, CD19+ and CD25+ cells are depleted prior to antigen loading of an APC population. In some embodiments, CD11b+, CD14+, CD19+ and CD25+ cells are depleted prior to antigen loading of an APC population. In some embodiments, the method comprises adding to any of the depleted APC population described above, an APC enriched cell PBMC-derived population that are depleted of CD3+ cell. In some embodiments, the APC enriched cell PBMC-derived population is depleted of CD3+ and cells depleted of any one or more of CD11b+, CD14+, CD19+, or CD25+. [0789] In some embodiments, a biological sample comprises peripheral blood mononuclear cells (PBMCs). In some embodiments, the method comprises adding to a PBMC sample, a composition comprising one or more antigenic peptides or nucleic acids encoding the same, thereby loading the APCs within the PBMCs with antigens for antigen presentation to T cells in the PBMC. [0790] In some embodiments, a method comprises: (a) obtaining a biological sample from a subject comprising at least one antigen-presenting cell (APC); (b) enriching cells expressing CD11c from the biological sample, thereby obtaining a CD11c+ cell enriched sample; (c) incubating the CD11c+ cell enriched sample with at least one cytokine or growth factor for a first time period; (d) incubating at WSGR Docket No.50401-795.601 least one peptide with the CD11c+ enriched sample of (c) for a second time period, thereby obtaining an APC peptide loaded sample; (e) incubating the APC peptide loaded sample with one or more cytokines or growth factors for a third time period, thereby obtaining a matured APC sample; (f) incubating APCs of the matured APC sample with a CD11b and/or CD14 and/or CD25 depleted sample comprising PBMCs for a fourth time period; (g) incubating the PBMCs with APCs of a matured APC sample for a fifth time period; (h) incubating the PBMCs with APCs of a matured APC sample for a sixth time period; and (i) administering at least one T cell of the PBMCs to a subject in need thereof. [0791] In some embodiments, a method comprises: (a) obtaining a biological sample from a subject comprising at least one antigen-presenting cell (APC); (b) enriching cells expressing CD14 from the biological sample, thereby obtaining a CD14+ cell enriched sample; (c) incubating the CD14+ cell enriched sample with at least one cytokine or growth factor for a first time period; (d) incubating at least one peptide with the CD14+ enriched sample of (c) for a second time period, thereby obtaining an APC peptide loaded sample; (e) incubating the APC peptide loaded sample with one or more cytokines or growth factors for a third time period, thereby obtaining a matured APC sample; (f) incubating APCs of the matured APC sample with a CD14 and/or CD25 depleted sample comprising PBMCs for a fourth time period; (g) incubating the PBMCs with APCs of a matured APC sample for a fifth time period; (h) incubating the PBMCs with APCs of a matured APC sample for a sixth time period; and (i) administering at least one T cell of the PBMCs to a subject in need thereof. [0792] In some embodiments, a method comprises: (a) obtaining a biological sample from a subject comprising at least one APC and at least one PBMC; (b) depleting cells expressing CD11b and/or CD19 from the biological sample, thereby obtaining a CD11b and/or CD19 cell depleted sample; (c) incubating the CD11b and/or CD19 cell depleted sample with FLT3L for a first time period; (d) incubating at least one peptide with the CD11b and/or CD19 cell depleted sample of (c) for a second time period, thereby obtaining an APC peptide loaded sample; (e) incubating the APC peptide loaded sample with the at least one PBMC for a third time period, thereby obtaining a first stimulated PBMC sample; (f) incubating a PBMC of the first stimulated PBMC sample with an APC of a matured APC sample for a fourth time period, thereby obtaining a second stimulated PBMC sample; (g) incubating a PBMC of the second stimulated PBMC sample with an APC of a matured APC sample for a fifth time period, thereby obtaining a third stimulated PBMC sample; (h) administering at least one T cell of the third stimulated PBMC sample to a subject in need thereof. [0793] In some embodiments, a method comprises: (a) obtaining a biological sample from a subject comprising at least one APC and at least one PBMC; (b) depleting cells expressing CD11b and/or CD19 and/or CD14 and/or CD25 from the biological sample, thereby obtaining a CD11b and/or CD19 cell depleted sample; (c) incubating the CD11b and/or CD19 and/or CD14 and/or CD25 cell WSGR Docket No.50401-795.601 depleted sample with FLT3L for a first time period; (d) incubating at least one peptide with the CD11b and/or CD19 and/or CD14 and/or CD25 cell depleted sample of (c) for a second time period, thereby obtaining an APC peptide loaded sample; (e) incubating the APC peptide loaded sample with the at least one PBMC for a third time period, thereby obtaining a first stimulated PBMC sample; (f) incubating a PBMC of the first stimulated PBMC sample with an APC of a matured APC sample for a fourth time period, thereby obtaining a second stimulated PBMC sample; (g) incubating a PBMC of the second stimulated PBMC sample with an APC of a matured APC sample for a fifth time period, thereby obtaining a third stimulated PBMC sample; (h) administering at least one T cell of the third stimulated PBMC sample to a subject in need thereof. [0794] In some embodiments, a method comprises: (a) obtaining a biological sample from a subject comprising at least one APC and at least one PBMC; (b) depleting cells expressing CD14 and/or CD25 from the biological sample, thereby obtaining a CD14 and/or CD25 cell depleted sample; (c) incubating the CD14 and/or CD25 cell depleted sample with FLT3L for a first time period; (d) incubating at least one peptide with the CD14 and/or CD25 cell depleted sample of (c) for a second time period, thereby obtaining an APC peptide loaded sample; (e) incubating the APC peptide loaded sample with the at least one PBMC for a third time period, thereby obtaining a first stimulated PBMC sample; (f) incubating a PBMC of the first stimulated PBMC sample with an APC of a matured APC sample for a fourth time period, thereby obtaining a second stimulated PBMC sample; (g) incubating a PBMC of the second stimulated PBMC sample with an APC of a matured APC sample for a fifth time period, thereby obtaining a third stimulated PBMC sample; (h) administering at least one T cell of the third stimulated PBMC sample to a subject in need thereof. [0795] In some embodiments, a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating an APC with a population of immune cells from a biological sample depleted of cells expressing CD14 and/or CD25. [0796] In some embodiments, provided herein is a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods of less than 28 days from incubating the population of immune cells with a first APC preparation of the one or more APC preparations, wherein at least one antigen specific memory T cell is expanded, or at least one antigen specific naïve T cell is induced. In some embodiments, provided herein is a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising incubating a population of immune cells from a biological sample with 3 or WSGR Docket No.50401-795.601 less APC preparations for 3 or less separate time periods, wherein at least one antigen specific memory T cell is expanded or at least one antigen specific naïve T cell is induced. [0797] In some embodiments, a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises contacting a population of immune cells (e.g., PBMCs) to APCs. In some embodiments, a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells (e.g., PBMCs) with APCs for a time period. In some embodiments, the population of immune cells is from a biological sample. In some embodiments, the population of immune cells is from a sample (e.g., a biological sample) depleted of CD14 expressing cells. In some embodiments, the population of immune cells is from a sample (e.g., a biological sample) depleted of CD25 expressing cells. In some embodiments, the population of immune cells is from a sample (e.g., a biological sample) depleted of CD14 expressing cells and CD25 expressing cells. [0798] In some embodiments, a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating an FMS- like tyrosine kinase 3 receptor ligand (FLT3L)-stimulated APC with a population of immune cells from a biological sample. In some embodiments, provided herein is a method of preparing a pharmaceutical composition comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence, the method comprising: incubating FMS-like tyrosine kinase 3 receptor ligand (FLT3L) with a population of immune cells from a biological sample for a first time period; and thereafter incubating at least one T cell of the biological sample with an APC. [0799] In some embodiments, a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises contacting a population of immune cells from a sample (e.g., a biological sample) with FMS-like tyrosine kinase 3 receptor ligand (FLT3L). In some embodiments, a method of preparing at least one antigen specific T cell comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises contacting a population of immune cells from a sample (e.g., a biological sample) with FMS-like tyrosine kinase 3 receptor ligand (FLT3L)-stimulated APCs. In some embodiments, a method of preparing at least one antigen specific T cell comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a sample (e.g., a biological sample) with FMS-like tyrosine kinase 3 receptor ligand (FLT3L)-stimulated APCs. In some embodiments, a method of preparing a pharmaceutical composition comprising at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating FMS-like tyrosine kinase 3 receptor ligand (FLT3L) with a population WSGR Docket No.50401-795.601 of immune cells from a biological sample (e.g., for a time period); and then contacting T cells of the biological sample to APCs. In some embodiments, a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises contacting a population of immune cells from a sample (e.g., a biological sample) to one or more APC preparations. In some embodiments, a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a sample (e.g., a biological sample) to one or more APC preparations for one or more separate time periods. In some embodiments, a method of preparing at least one antigen specific T cell comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a sample (e.g., a biological sample) to one or more APC preparations for 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 separate time periods. In some embodiments, the one or more separate time periods is less than 28 days calculated from incubating the population of immune cells with a first APC preparation of the one or more APC preparations. [0800] In some embodiments, a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells to APCs for a time period, wherein the population of immune cells is from a biological sample comprising PBMCs. In some embodiments, a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells to APCs for a time period, wherein the population of immune cells is from a biological sample depleted of CD14 and/or CD25 expressing cells. [0801] In some embodiments, a method of preparing antigen specific T cells comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with FMS-like tyrosine kinase 3 receptor ligand (FLT3L)- stimulated APCs for a time period. [0802] In some embodiments, a method of preparing a pharmaceutical composition comprising antigen specific T cells comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating FMS-like tyrosine kinase 3 receptor ligand (FLT3L) with a population of immune cells from a biological sample; and then contacting T cells of the biological sample with APCs. [0803] In some embodiments, a method of preparing antigen specific T cells comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods, thereby inducing or expanding antigen specific T cells, wherein the one or more separate time periods is less than 28 days calculated from incubating the population of immune cells with a WSGR Docket No.50401-795.601 first APC preparation of the one or more APC preparations. In some embodiments, incubating a population of immune cells from a biological sample with one or more APC preparations for one or more separate time periods is performed in a medium containing IL-7, IL-15, or a combination thereof. In some embodiments, the medium further comprises an indoleamine 2,3-dioxygenase-1 (IDO) inhibitor, an anti-PD-1 antibody, IL-12, or a combination thereof. The IDO inhibitor can be epacadostat, navoximod, 1-Methyltryptophan, or a combination thereof. In some embodiments, the IDO inhibitor can increase the number of antigen-specific CD8+ cells. In some embodiments, the IDO inhibitor can maintain the functional profile of memory CD8+ T cell responses. The PD-1 antibody can increase the absolute number of antigen-specific memory CD8+ T cell responses. The PD-1 antibody can increase proliferation rate of the cells treated with such antibody. The additional of IL- 12 can result in an increase of antigen-specific cells and/or an increase in the frequency of CD8+ T cells. [0804] In some embodiments, a method of preparing antigen specific T cells comprising a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells comprising from a biological sample with one or more APC preparations for one or more separate time periods, thereby expanding or inducing antigen specific T cells, wherein a percentage of antigen specific T cells, antigen specific CD4+ T cells, or antigen specific CD8+ T cells is at least about 0.00001%, 0.00002%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of total T cells, total CD4+ T cells, total CD8+ T cells, total immune cells, or total cells. [0805] In some embodiments, a method of preparing antigen specific T cells comprises a T-cell receptor (TCR) specific to at least one antigen peptide sequence comprises incubating a population of immune cells from a biological sample with 3 or less APC preparations for 3 or less separate time periods, thereby stimulating T cells to become antigen specific T cells. [0806] In some embodiments, the population of immune cells is from a biological sample depleted of CD14 and/or CD25 expressing cells. In some embodiments, the APCs are FMS-like tyrosine kinase 3 receptor ligand (FLT3L)-stimulated APCs. In some embodiments, the APCs comprise one or more APC preparations. In some embodiments, the APC preparations comprise 3 or less APC preparations. In some embodiments, the APC preparations are incubated with the immune cells sequentially within one or more separate time periods. [0807] In some embodiments, the biological sample is from a subject. In some embodiments, the subject is a human. For example, the subject can be a patient or a donor. In some embodiments, the subject has a disease or disorder. In some embodiments, the disease or disorder is cancer. In some embodiments, the antigen specific T cells comprise CD4+ and/or CD8+ T cells. In some WSGR Docket No.50401-795.601 embodiments, the antigen specific T cells comprise CD4 enriched T cells and/or CD8 enriched T cells. For example, a CD4+ T cell and/or CD8+ T cell can be isolated from, enriched from, or purified from a biological sample from a subject comprising PBMCs. In some embodiments, the antigen specific T cells are naïve CD4+ and/or naïve CD8+ T cells. In some embodiments, the antigen specific T cells are memory CD4+ and/or memory CD8+ T cells. [0808] In some embodiments, each of the at least one antigen peptide sequence binds to a protein encoded by an HLA allele expressed by the subject. In some embodiments, each of the at least one antigen peptide sequence is not present in non-cancer cells of the subject. In some embodiments, each of the at least one antigen peptide sequences is encoded by genome of a cancer cell. In some embodiments, one or more of the at least one antigen peptide sequence has a length of from 8-50 naturally occurring amino acids. In some embodiments, the at least one antigen peptide sequence comprises a plurality of antigen peptide sequences. In some embodiments, the plurality of antigen peptide sequences comprises from 2-50, 3-50, 4-50, 5-5-, 6-50, 7-50, 8-50, 9-50, or 10-50 antigen peptide sequences. [0809] In some embodiments, the APCs comprise APCs loaded with one or more antigen peptides comprising one or more of the at least one antigen peptide sequence. In some embodiments, the APCs are autologous APCs or allogenic APCs. In some embodiments, the APCs comprise dendritic cells (DCs). [0810] In some embodiments, a method comprises depleting CD14 and/or CD25 expressing cells from the biological sample. In some embodiments, depleting CD14+ cells comprises contacting a CD14 binding agent to the APCs. In some embodiments, the APCs are derived from CD14+ monocytes. In some embodiments, the APCs are enriched from the biological sample. For example, an APC can be isolated from, enriched from, or purified from a biological sample from a subject comprising PBMCs. [0811] In some embodiments, the APCs are stimulated with one or more cytokines or growth factors. In some embodiments, the one or more cytokines or growth factors comprise GM-CSF, IL-4, FLT3L, or a combination thereof. In some embodiments, the one or more cytokines or growth factors comprise IL-4, IFN-γ, LPS, GM-CSF, TNF-α, IL-1β, PGE1, IL-6, IL-7 or a combination thereof. [0812] In some embodiments, the APCs are from a second biological sample. In some embodiments, the second biological sample is from the same subject. [0813] In some embodiments, a percentage of antigen specific T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells. In some embodiments, a percentage of antigen specific T cells in the method is from about 0.1% to about 5%, from about 5 % to 10%, from about 10% to 15%, from about 15% to 20%, from about 20% to 25%, from about 25% to 30%, from about 30% to 35%, WSGR Docket No.50401-795.601 from about 35% to about 40%, from about 40% to about 45%, from about 45% to about 50%, from about 50% to about 55%, from about 55% to about 60%, from about 60% to 65%, or from about 65% to about 70% of total T cells or total immune cells. In some embodiments, a percentage of antigen specific CD8+ T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells. In some embodiments, a percentage of antigen specific naïve CD8+ T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells. In some embodiments, a percentage of antigen specific memory CD8+ T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells. In some embodiments, a percentage of antigen specific CD4+ T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells. In some embodiments, a percentage of antigen specific CD4+ T cells in the method is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total T cells or total immune cells. In some embodiments, a percentage of antigen specific T cells in the biological sample is at most about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%. In some embodiments, a percentage of antigen specific CD8+ T cells in the biological sample is at most about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%. In some embodiments, a percentage of antigen specific naïve CD8+ T cells in the biological sample is at most about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%. In some embodiments, a percentage of antigen specific memory CD8+ T cells in the biological sample is at most about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%. In some embodiments, a percentage of antigen specific CD4+ T cells in the biological sample is at most about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%. [0814] In some embodiments, a biological sample is freshly obtained from a subject or is a frozen sample. [0815] In some embodiments, a method comprises incubating one or more of the APC preparations with a first medium comprising at least one cytokine or growth factor for a first time period. In some embodiments, the first time period is at lease 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17, or 18 days. In some embodiments, the first time period is no more than 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 days. In some embodiments, the first time period is at least 1, 23, 4, 5, 6, 7, 8, or 9 days. In some embodiments, the first time period is no more than 3, 4, 5, 6, 7, 8, 9, or 10 days. WSGR Docket No.50401-795.601 In some embodiments, the at least one cytokine or growth factor comprises GM-CSF, IL-4, FLT3L, TNF-α, IL-1β, PGE1, IL-6, IL-7, IFN-γ, LPS, IFN-α, R848, LPS, ss-rna40, poly I:C, or any combination thereof. [0816] In some embodiments, a method comprises incubating one or more of the APC preparations with at least one peptide for a second time period. In some embodiments, the second time period is no more than 1 hour. [0817] In some embodiments, a method comprises incubating one or more of the APC preparations with a second medium comprising one or more cytokines or growth factors for a third time period, thereby obtaining matured APCs. In some embodiments, the one or more cytokines or growth factors comprises GM-CSF (granulocyte macrophage colony-stimulating factor), IL-4, FLT3L, IFN-γ, LPS, TNF-α, IL-1β, PGE1, IL-6, IL-7, IFN-α, R848 (resiquimod), LPS, ss-rna40, poly I:C, CpG, or a combination thereof. In some embodiments, the third time period is no more than 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 days. In some embodiments, the third time period is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 days. In some embodiments, the third time period is no more than 2, 3, 4, or 5 days. In some embodiments, the third time period is at least 1, 2, 3, or 4 days. [0818] In some embodiments, the method further comprises removing the one or more cytokines or growth factors of the second medium after the third time period and before a start of the fourth time period. Antigen loaded PBMCs for T cell induction in vitro [0819] The NEO-STIM process may comprise methods of generating antigen loaded PBMCs for induction of T cells (e.g., RAS-specific T cells). [0820] In some embodiments, the methods provided herein comprise isolating PBMCs from a human blood sample, and directly loading the PBMCs with antigens. PBMCs directly contacted with antigens can readily take up antigens by phagocytosis and present antigens to T cells that can be in the culture or added to the culture. In some embodiments, the methods provided herein comprise isolating PBMCs from a human blood sample, and nucleofecting or electroporating a polynucleotide, such as an mRNA, that encodes one or more antigens into the PBMCs. In some embodiments, antigens delivered to PBMCs, instead of antigen-presenting cells maturing to DCs, provides a great advantage in terms of time and manufacturing efficiency. The PBMCs can be further depleted of one or more cell types. In some embodiments, the PBMCs can be depleted of CD3+ cells for an initial period of antigen loading and the CD3+ cells returned to the culture for the PBMCs to stimulate the CD3+ T cells. In some embodiments, the PBMCs can be depleted of CD25+ cells. In some embodiments, the PBMCs can be depleted of CD14+ cells. In some embodiments, the PBMCs can be depleted of CD19+ cells. In some embodiments, the PBMCs can be depleted of both CD14 and CD25 expressing WSGR Docket No.50401-795.601 cells. In some embodiments, CD11b+ cells are depleted from the PBMC sample before antigen loading. In some embodiments, CD11b+ and CD25+ cells are depleted from the PBMC sample before antigen loading. [0821] In some embodiments, the PBMCs isolated from a human blood sample can be handled as minimally as possible prior to loading with antigens. Increased handling of PBMCs, for example freezing and thawing cells, multiple cell depletion steps, etc., can impair cell health and viability. [0822] In some embodiments, the PBMCs are allogeneic to the subject of therapy. In some embodiments the PBMCs are allogeneic to the subject of adoptive cell therapy with antigen specific T cells. [0823] In some embodiments, the PBMCs are HLA-matched for the subject of therapy. In some embodiments, the PBMCs are allogeneic, and matched for the subject’s HLA subtypes, whereas the CD3+ T cells are autologous. The PBMCs are loaded with the respective antigens (e.g., derived from analysis of a peptide presentation analysis platform such as RECON), cocultured with subject’s PBMC comprising T cells in order to stimulate antigen specific T cells. [0824] In some embodiments, mRNA is used as the immunogen for uptake and antigen presenting. One advantage of using mRNA over peptide antigens to load PBMCs is that RNA is self adjuvanting, and does not require additional adjuvants. Another advantage of using mRNA is that the peptides are processed and presented endogenously. In some embodiments, the mRNA comprises shortmer constructs, encoding 9-10 amino acid peptides comprising an epitope. In some embodiments, the mRNA comprises longmer constructs, encoding bout 25 amino acid peptides. In some embodiments, the mRNA comprises a concatenation of multiple epitopes. In some embodiments, the concatemers can comprise one or more epitopes from the same antigenic protein. In some embodiments, the concatemers can comprise one or epitopes from several different antigenic proteins. Several embodiments are described in the Examples section. Antigen loading of PBMCs by antigen loading can comprise various mechanisms of delivery ad incorporation of nucleic acid into the PBMCs. In some embodiments, the delivery or mechanism of incorporation includes transfection, electroporation, nucleofection, chemical delivery, for example, lipid encapsulated, or liposome mediated delivery. [0825] Use of antigen loaded PBMCs to stimulate T cells can save the maturation time needed in a method that generates DCs from a PBMC sample prior to T cell stimulation. In some embodiments, use of antigen loaded PBMCs, for example, mRNA loaded PBMCs as APCs reduces the total manufacturing time by 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In some embodiments, use of antigen loaded PBMCs as APCs reduces the total manufacturing time by 3 days. In some embodiments, use of antigen loaded PBMCs as APCs reduces the total manufacturing time by 4 days. In some embodiments, use of antigen loaded PBMCs as APCs reduces the total manufacturing time by 5 days. In some embodiments, use of antigen loaded PBMCs as APCs reduces the total manufacturing time WSGR Docket No.50401-795.601 by 6 days. In some embodiments, use of antigen loaded PBMCs as APCs reduces the total manufacturing time by 7 days. [0826] In some embodiments, use of mRNA as antigen can be preferred because it is easy to design and manufacture nucleic acids, and transfect the PBMCs. In some embodiments, mRNA loaded PBMCs can stimulate T cells and generate higher antigen specific T cells. In some embodiments, mRNA loaded PBMCs can stimulate T cells and generate higher yield of antigen specific T cells. In some embodiments, mRNA loaded PBMCs can stimulate T cells and generate antigen specific T cells that have higher representation of the input antigens, i.e., reactive to diverse antigens. In some embodiments, mRNA loaded PBMCs can stimulate T cells that have at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more antigen reactivity in the pool of expanded cells. In some embodiments, the mRNA loaded PBMCs can stimulate T cells that have at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more antigen reactivity than conventional antigen loaded APCs (such as peptide loaded DCs). T-Cell Receptors [0827] Also disclosed herein are T cell receptors (TCRs) and recombinant nucleic acids encoding the same. In some aspects, provided herein is a recombinant nucleic acid encoding a TCR that recognizes epitopes (e.g., epitopes derived from RAS) derived from a protein encoded by a gene of a cancer cell. The T-cell receptor (TCR) can comprise a TCR beta chain construct and a TCR alpha chain construct. [0828] The ability of T cells to recognize antigens associated with infectious organisms or cancers is conferred by its TCR, which is made up of both an alpha (α) chain and a beta (β) chain or a gamma (γ) and a delta (δ) chain. The proteins which make up these chains are encoded by DNA, which employs a unique mechanism for generating the diversity of the TCR. This multi-subunit immune recognition receptor can associate with the CD3 complex and bind peptides presented by the MHC class I and II proteins on the surface of antigen-presenting cells (APCs). The first signal in activation of T cells can be provided by binding of the T-cell receptor to a short peptide presented by the MHC on another cell. This ensures that only a T cell with a TCR specific to that peptide is activated. The partner cell is usually an antigen-presenting cell such as a professional antigen-presenting cell, usually a dendritic cell in the case of naive responses, although B-cells and macrophages can be important APCs. Binding of a TCR to the antigenic peptide on the APC can be a central event in T cell activation, which occurs at an immunological synapse at the point of contact between the T cell and the APC. [0829] Each TCR can comprise variable complementarity determining regions (CDRs), as well as framework regions (FRs) and a constant region. The TCR described herein may be in soluble form. The TCR described herein may not comprise a constant region. The TCR described herein may comprise a functional fragment of a full-length TCR. The TCR described herein may comprise the variable region of the alpha chain or beta chain only. The amino acid sequence of the third WSGR Docket No.50401-795.601 complementarity-determining region (CDR3) loops of the alpha (or α) and beta (or β) chain variable domains largely determines the sequence diversity of αβ T cells arising from recombination between variable (Vβ), diversity (Dβ), and joining (Jβ) gene segments in the β chain locus, and between analogous Vα and Jα gene segments in the α chain locus, respectively. The existence of multiple such gene segments in the TCR α and β chain loci allows for a large number of distinct CDR3 sequences to be encoded. Independent addition and deletion of nucleotides at the Vβ-Dβ, Dβ-Jβ, and Vα-Jα junctions during the process of TCR gene rearrangement further increases CDR3 sequence diversity. In this respect, immunocompetence is reflected in the diversity of TCRs. The γδ TCR is distinctive from the αβ TCR in that it encodes a receptor that interacts closely with the innate immune system. TCRγδ, is expressed early in development, has specialized anatomical distribution, has unique pathogen and small-molecule specificities, and has a broad spectrum of innate and adaptive cellular interactions. Early in ontogeny, as the restricted subsets of TCRγδ cells populate various tissues prenatally, a biased pattern of TCRγ V and J segment expression is established. [0830] TCRs can bind to a peptide: MHC complex. In some cases, the TCR can bind to an MHC peptide complex comprising an epitope from an antigen or candidate antigen described herein. In some cases, the TCR can bind to an MHC peptide complex comprising an epitope of protein encoded by the genome of a cancer cell. The binding of the TCR complex and the epitope bound with the MHC molecule (e.g., MHC class I or MHC class II) can trigger signal transduction pathways that lead to regulation of immune responses against the antigenic peptide. In some embodiments, the TCR binds to an MHC-peptide complex with a KD or an IC50 of 1 μM to 1 nM. In some embodiments, the TCR binds to an MHC-peptide complex with a KD or an IC50 of less than 500 nM, 250 nM, 150 nM, 100 nM, 50 nM, 25 nM or 10 nM. In some embodiments, the TCR binds to an MHC-peptide complex with a KD or an IC50 of less than 500 nM. In some embodiments, the TCR binds to an MHC-peptide complex with a KD or an IC50 of less than 250 nM. In some embodiments, the TCR binds to an MHC-peptide complex with a KD or an IC50 of less than 150 nM. In some embodiments, the TCR binds to an MHC-peptide complex with a KD or an IC50 of less than 100 nM. In some embodiments, the TCR binds to an MHC-peptide complex with a KD or an IC50 of less than 50 nM. In some embodiments, the TCR binds to an MHC-peptide complex with a KD or an IC50 of less than 25 nM. In some embodiments, the TCR binds to an MHC-peptide complex with a KD or an IC50 of less than 10 nM. [0831] In some embodiments, the nucleic acid is operably linked to a promoter. [0832] In various embodiments, the nucleic acid sequence encoding a TCR is codon optimized. [0833] In some embodiments, the TCR sequence is comprised of human sequences. In some embodiments, the TCR sequence is comprised of non-human animal sequences that have been WSGR Docket No.50401-795.601 humanized using any method of humanization known in the art. The TCRs provided herein can be engineered TCRs. [0834] In some embodiments, the TCR comprises a TCR beta chain construct. In some embodiments the TCR comprises a TCR alpha chain construct. In some embodiments, the TCR comprises a TCR beta chain construct and a TCR alpha chain construct. In some embodiments, the TCR binds to a peptide:MHC complex. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 5 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 27, 58-62 and 65-72 and a human MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA- A*03:05. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 7 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 27, 58-62 and 65-72 and a human MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA- C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 5 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 28, 75-79 and a human MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 7 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 28, 75-79 and a human MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 5 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 29, 81, 82, and 1096 and a human MHC encoded by an HLA allele selected from the group consisting of HLA- DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. In some embodiments, the peptide:MHC complex comprises a RAS epitope sequence having at least 7 consecutive amino acids of a sequence selected from the group consisting of SEQ ID NO: 29, 81, 82, and 1096 and a human MHC encoded by an HLA allele selected from the group consisting of HLA- DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. [0835] In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 58. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence WSGR Docket No.50401-795.601 having at least 80% sequence identity to a sequence of SEQ ID NO: 59. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 60. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 61. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 62. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 65. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 66. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 67. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 68. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 69. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 70. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 71. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 72. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 75. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 76. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least WSGR Docket No.50401-795.601 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 77. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 78. In some embodiments the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 79. In some embodiments the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 29. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 81. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 82. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to a sequence of SEQ ID NO: 1096. [0836] In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 58. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 59. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 60. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 61. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 62. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 65. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 66. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 67. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 68. In some embodiments, the peptide:MHC complex comprises the RAS WSGR Docket No.50401-795.601 epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 69. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 70. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 71. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 72. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 75. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 76. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 77. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 78. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 79. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 29. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 81. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 82. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence having at least 90% sequence identity to a sequence of SEQ ID NO: 1096. [0837] In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 58. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 59. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 60. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 61. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 62. In some embodiments the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 65. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 66. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 67. In some embodiments, the peptide:MHC complex comprises the RAS WSGR Docket No.50401-795.601 epitope sequence having a sequence according to SEQ ID NO: 68. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 69. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 70. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 71. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 72. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 75. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 76. In some embodiments the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 77. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 78. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 79. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 29. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 81. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 82. In some embodiments, the peptide:MHC complex comprises the RAS epitope sequence having a sequence according to SEQ ID NO: 1096. [0838] In some embodiments, the TCR is expressed by a cell. In some embodiments, the cell is an immune cell. In some embodiments, the recombinant nucleic acid encoding the TCR is expressed by a cell. In some embodiments, the TCR is a soluble TCR. Pharmaceutical Compositions [0839] Provided herein are compositions (e.g., pharmaceutical compositions) comprising a population of immune cells. The compositions can comprise at least one antigen specific T cells comprising a T cell receptor (TCR). The compositions can comprise at least one antigen specific T cell comprising a TCR specific to at least one antigen peptide sequence. For example, the compositions provided herein can comprise a TCR or a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR where the TCR can recognize and bind to a peptide:MHC complex comprising (i) a RAS epitope sequence, and (ii) a human MHC encoded by an HLA allele. For another example, the compositions provided herein can comprise an immune cell comprising a TCR or a recombinant nucleic acid encoding the TCR, where the TCR can recognize and bind to a peptide:MHC complex comprising (i) a RAS epitope sequence, and (ii) a human MHC encoded by an HLA allele. WSGR Docket No.50401-795.601 [0840] Also provided herein are compositions comprising a RAS polypeptide or a recombinant nucleic acid encoding the RAS polypeptide. The RAS polypeptide can comprise a full-length RAS protein or one or more RAS epitopes described herein. The recombinant nucleic acid encoding the RAS polypeptide can be an RNA sequence, such as a messenger RNA (mRNA) sequence. The RNA sequence encoding the RAS polypeptide can comprise the corresponding RNA sequence of any one of the DNA sequences described herein. [0841] Also provided herein are compositions comprising T cell receptors (TCRs) and recombinant nucleic acids encoding the same. In some embodiments, the recombinant nucleic acid encoding the TCR is expressed by a cell. In some embodiments, the TCR is a soluble TCR. [0842] Pharmaceutical compositions can be formulated using one or more physiologically acceptable carriers including excipients and auxiliaries which facilitate processing of the active agents into preparations which can be used pharmaceutically. Proper formulation can be dependent upon the route of administration chosen. Any of the well-known techniques, carriers, and excipients can be used as suitable and as understood in the art. [0843] In some cases, a pharmaceutical composition is formulated as cell based therapeutic, e.g., a T cell therapeutic. In some embodiments, the pharmaceutical composition comprises a peptide-based therapy, a nucleic acid-based therapy, an antibody based therapy, and/or a cell based therapy. In some embodiments, a pharmaceutical composition comprises a peptide-based therapeutic, or nucleic acid based therapeutic in which the nucleic acid encodes the polypeptides. In some embodiments, a pharmaceutical composition comprises a peptide-based therapeutic, or nucleic acid based therapeutic in which the nucleic acid encodes the polypeptides; wherein the peptide-based therapeutic, or nucleic acid based therapeutic are comprised in a cell, wherein the cell is a T cell. In some embodiments, a pharmaceutical composition comprises as an antibody based therapeutic. A composition can comprise T cells specific for two or more immunogenic antigen or neoantigen peptides. [0844] In one aspect, provided herein is a pharmaceutical composition comprising (a) a population of immune cells comprising T cells from a biological sample, wherein the T cells comprise at least one antigen specific T cell (e.g., T cell specific for a RAS epitope) that is an APC-stimulated T cell and comprises a T cell receptor (TCR) specific to at least one antigen peptide sequence, wherein the APC is a FLT3L-stimulated APC; and (b) a pharmaceutically acceptable excipient. [0845] In one aspect, provided herein is a pharmaceutical composition comprising: (a) a population of immune cells from a biological sample comprising at least one antigen specific T cell comprising a T cell receptor (TCR) specific to at least one antigen peptide sequence, and (b) a pharmaceutically acceptable excipient; wherein an amount of immune cells expressing CD14 and/or CD25 in the population is proportionally different from an amount of immune cells expressing CD14 and/or CD25 in the biological sample. In some embodiments, the at least one antigen specific T cell comprises at WSGR Docket No.50401-795.601 least one APC-stimulated T cell. In some embodiments, the amount of immune cells expressing CD14 and/or CD25 in the population is proportionally less than the amount of immune cells expressing CD14 and/or CD25 in the biological sample. In some embodiments, the amount of immune cells expressing CD14 and/or CD25 in the population is proportionally more than the amount of immune cells expressing CD14 and/or CD25 in the biological sample. In some embodiments, the at least one antigen specific T cell comprises at least one CD4+ T cell. In some embodiments, the at least one antigen specific T cell comprises at least one CD8+ T cell. In some embodiments, the at least one antigen specific T cell comprises at least one CD4 enriched T cell. In some embodiments, the at least one antigen specific T cell comprises at least one CD8 enriched T cell. In some embodiments, the at least one antigen specific T cell comprises a memory T cell. In some embodiments, the at least one antigen specific T cell comprises a memory CD4+ T cell. In some embodiments, the at least one antigen specific T cell comprises a memory CD8+ T cell. In some embodiments, a percentage of the at least one antigen specific T cell in the composition is at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of total T cells or total immune cells. In some embodiments, a percentage of at least one antigen specific CD8+ T cell in the composition is at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of total CD4+ T cells, total CD8+ T cells, total T cells or total immune cells. [0846] Pharmaceutical compositions can include, in addition to active ingredient, a pharmaceutically acceptable excipient, carrier, buffer, stabilizer or other materials well known to those skilled in the art. Such materials can be non-toxic and may not interfere with the efficacy of the active ingredient. The precise nature of the carrier or other material will depend on the route of administration. [0847] Acceptable carriers, excipients, or stabilizers are those that are non-toxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn- WSGR Docket No.50401-795.601 protein complexes); and/or non-ionic surfactants such as TWEEN®, PLURONICS® or polyethylene glycol (PEG). [0848] Acceptable carriers are physiologically acceptable to the administered patient and retain the therapeutic properties of the compounds with/in which it is administered. Acceptable carriers and their formulations are generally described in, for example, Remington’ pharmaceutical Sciences (18th ed. A. Gennaro, Mack Publishing Co., Easton, PA 1990). One example of carrier is physiological saline. A pharmaceutically acceptable carrier is 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 compounds from the administration site of one organ, or portion of the body, to another organ, or portion of the body, or in an in vitro assay system. Acceptable carriers are compatible with the other ingredients of the formulation and not injurious to a subject to whom it is administered. Nor should an acceptable carrier alter the specific activity of the neoantigens. [0849] In one aspect, provided herein are pharmaceutically acceptable or physiologically acceptable compositions including solvents (aqueous or non-aqueous), solutions, emulsions, dispersion media, coatings, isotonic and absorption promoting or delaying agents, compatible with pharmaceutical administration. Pharmaceutical compositions or pharmaceutical formulations therefore refer to a composition suitable for pharmaceutical use in a subject. Compositions can be formulated to be compatible with a particular route of administration (i.e., systemic or local). Thus, compositions include carriers, diluents, or excipients suitable for administration by various routes. [0850] In some embodiments, a composition can further comprise an acceptable additive in order to improve the stability of immune cells in the composition. Acceptable additives may not alter the specific activity of the immune cells. Examples of acceptable additives include, but are not limited to, a sugar such as mannitol, sorbitol, glucose, xylitol, trehalose, sorbose, sucrose, galactose, dextran, dextrose, fructose, lactose and mixtures thereof. Acceptable additives can be combined with acceptable carriers and/or excipients such as dextrose. Alternatively, examples of acceptable additives include, but are not limited to, a surfactant such as polysorbate 20 or polysorbate 80 to increase stability of the peptide and decrease gelling of the solution. The surfactant can be added to the composition in an amount of 0.01% to 5% of the solution. Addition of such acceptable additives increases the stability and half-life of the composition in storage. [0851] The pharmaceutical composition can be administered, for example, by injection. Compositions for injection include aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, or phosphate buffered saline (PBS). The carrier can be a solvent or dispersion medium containing, for WSGR Docket No.50401-795.601 example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. Fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Antibacterial and antifungal agents include, for example, parabens, chlorobutanol, phenol, ascorbic acid and thimerosal. Isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, and sodium chloride can be included in the composition. The resulting solutions can be packaged for use as is, or lyophilized; the lyophilized preparation can later be combined with a sterile solution prior to administration. For intravenous, injection, or injection at the site of affliction, the active ingredient will be in the form of a parenterally acceptable aqueous solution which is pyrogen-free and has suitable pH, isotonicity and stability. Those of relevant skill in the art are well able to prepare suitable solutions using, for example, isotonic vehicles such as Sodium Chloride Injection, Ringer’s Injection, Lactated Ringer’s Injection. Preservatives, stabilizers, buffers, antioxidants and/or other additives can be included, as needed. Sterile injectable solutions can be prepared by incorporating an active ingredient in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions can be prepared by incorporating the active ingredient into a sterile vehicle which contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the methods of preparation can be vacuum drying and freeze drying which yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof. [0852] Compositions can be conventionally administered intravenously, such as by injection of a unit dose, for example. For injection, an active ingredient can be in the form of a parenterally acceptable aqueous solution which is substantially pyrogen-free and has suitable pH, isotonicity and stability. One can prepare suitable solutions using, for example, isotonic vehicles such as Sodium Chloride Injection, Ringer’s Injection, Lactated Ringer’s Injection. Preservatives, stabilizers, buffers, antioxidants and/or other additives can be included. Additionally, compositions can be administered via aerosolization. [0853] When the compositions are considered for use in medicaments or any of the methods provided herein, it is contemplated that the composition can be substantially free of pyrogens such that the composition will not cause an inflammatory reaction or an unsafe allergic reaction when administered to a human patient. Testing compositions for pyrogens and preparing compositions substantially free of pyrogens are well understood to one or ordinary skill of the art and can be accomplished using commercially available kits. [0854] Acceptable carriers can contain a compound that acts as a stabilizing agent, increases or delays absorption, or increases or delays clearance. Such compounds include, for example, WSGR Docket No.50401-795.601 carbohydrates, such as glucose, sucrose, or dextrans; low molecular weight proteins; compositions that reduce the clearance or hydrolysis of peptides; or excipients or other stabilizers and/or buffers. Agents that delay absorption include, for example, aluminum monostearate and gelatin. Detergents can also be used to stabilize or to increase or decrease the absorption of the pharmaceutical composition, including liposomal carriers. To protect from digestion the compound can be complexed with a composition to render it resistant to acidic and enzymatic hydrolysis, or the compound can be complexed in an appropriately resistant carrier such as a liposome. Means of protecting compounds from digestion are known in the art (e.g., Fix (1996) Pharm Res.13:17601764; Samanen (1996) J. Pharm. Pharmacol.48:119135; and U.S. Pat. No.5,391,377). [0855] The compositions can be administered in a manner compatible with the dosage formulation, and in a therapeutically effective amount. The quantity to be administered can depend on the subject to be treated, capacity of the subject’s immune system to utilize the active ingredient, and degree of binding capacity desired. Precise amounts of active ingredient required to be administered can depend on the judgment of the practitioner and can be peculiar to each individual. Suitable regimes for initial administration and booster shots can also be variable, but can be typified by an initial administration followed by repeated doses at one or more hour intervals by a subsequent injection or other administration. Alternatively, continuous intravenous infusions sufficient to maintain concentrations in the blood can be contemplated. [0856] A pharmaceutical composition can be encapsulated within liposomes using well-known technology. Biodegradable microspheres can also be employed as carriers for the pharmaceutical compositions of this present disclosure. [0857] The pharmaceutical composition can be administered in liposomes or microspheres (or microparticles). Methods for preparing liposomes and microspheres for administration to a patient are well known to those of skill in the art. Essentially, material is dissolved in an aqueous solution, the appropriate phospholipids and lipids added, along with surfactants if required, and the material dialyzed or sonicated, as necessary. [0858] Microspheres formed of polymers or proteins are well known to those skilled in the art, and can be tailored for passage through the gastrointestinal tract directly into the blood stream. Alternatively, the compound can be incorporated and the microspheres, or composite of microspheres, implanted for slow release over a period of time ranging from days to months. [0859] A pharmaceutical composition comprising an active agent such as an immune cell described herein, in combination with one or more adjuvants can be formulated in conventional manner using one or more physiologically acceptable carriers, comprising excipients, diluents, and/or auxiliaries, e.g., which facilitate processing of the active agents into preparations that can be administered. Proper formulation can depend at least in part upon the route of administration chosen. The agent(s) WSGR Docket No.50401-795.601 described herein can be delivered to a patient using a number of routes or modes of administration, including oral, buccal, topical, rectal, transdermal, transmucosal, subcutaneous, intravenous, and intramuscular applications, as well as by inhalation. [0860] The active agents can be formulated for parenteral administration (e.g., by injection, for example bolus injection or continuous infusion) and can be presented in unit dose form in ampoules, pre-filled syringes, small volume infusion or in multi-dose containers with an added preservative. The compositions can take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, for example solutions in aqueous polyethylene glycol. [0861] In some embodiments, the pharmaceutical composition comprises a preservative or stabilizer. In some embodiments the preservative or stabilizer is selected from a cytokine, a growth factor or an adjuvant or a chemical substance. In some embodiments, the composition comprises at least one agent that helps preserve cell viability through at least one cycle of freeze-thaw. In some embodiments, the composition comprises at least one agent that helps preserve cell viability through at least more than one cycle of freeze-thaw. [0862] For injectable formulations, the vehicle can be chosen from those known in art to be suitable, including aqueous solutions or oil suspensions, or emulsions, with sesame oil, corn oil, cottonseed oil, or peanut oil, as well as elixirs, mannitol, dextrose, or a sterile aqueous solution, and similar pharmaceutical vehicles. The formulation can also comprise polymer compositions which are biocompatible, biodegradable, such as poly(lactic-co-glycolic)acid. These materials can be made into micro or nanospheres, loaded with drug and further coated or derivatized to provide superior sustained release performance. Vehicles suitable for periocular or intraocular injection include, for example, suspensions of therapeutic agent in injection grade water, liposomes and vehicles suitable for lipophilic substances. Other vehicles for periocular or intraocular injection are well known in the art. [0863] In some instances, pharmaceutical composition is formulated in accordance with routine procedures as a pharmaceutical composition adapted for intravenous administration to human beings. Typically, compositions for intravenous administration are solutions in sterile isotonic aqueous buffer. Where necessary, the composition can also include a solubilizing agent and a local anesthetic such as lidocaine to ease pain at the site of the injection. Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachette indicating the quantity of active agent. Where the composition is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline. Where the composition is administered by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients can be mixed prior to administration. WSGR Docket No.50401-795.601 [0864] Pharmaceutical compositions comprising, for example, an active agent such as immune cells disclosed herein, in combination with one or more adjuvants can be formulated to comprise certain molar ratios. For example, molar ratios of about 99:1 to about 1:99 of an active agent such as an immune cell described herein, in combination with one or more adjuvants can be used. In some instances, the range of molar ratios of an active agent such as an immune cell described herein, in combination with one or more adjuvants can be selected from about 80:20 to about 20:80; about 75:25 to about 25:75, about 70:30 to about 30:70, about 66:33 to about 33:66, about 60:40 to about 40:60; about 50:50; and about 90:10 to about 10:90. The molar ratio of an active agent such as an immune cell described herein, in combination with one or more adjuvants can be about 1:9, and in some cases can be about 1:1. The active agent such as an immune cell described herein, in combination with one or more adjuvants can be formulated together, in the same dosage unit e.g., in one vial, suppository, tablet, capsule, an aerosol spray; or each agent, form, and/or compound can be formulated in separate units, e.g., two vials, suppositories, tablets, two capsules, a tablet and a vial, an aerosol spray, and the like. [0865] In some embodiments, the pharmaceutical composition comprises a nanoparticle. In some embodiments, the nanoparticle is a lipid nanoparticle or a liposome. In some embodiments, the particle is a lipoplex. In some embodiments, the lipid is comprised in a vesicle encapsulating said RNA. The vesicle may be a multilamellar vesicle, an unilamellar vesicle, or a mixture thereof. The vesicle may be a liposome. [0866] In some embodiments,, the nanoparticles are lipoplexes comprising DOTMA and DOPE in a molar ratio of 10:0 to 1:9, in some cases 8:2 to 3:7, and in some cases of 7:3 to 5:5 and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.8:2 to 0.8:2, in some cases 1.6:2 to 1:2, in some cases 1.4:2 to 1.1:2 and in some cases about 1.2:2. [0867] In some embodiments, the nanoparticles are lipoplexes comprising DOTMA and Cholesterol in a molar ratio of 10:0 to 1:9, in some cases 8:2 to 3:7, and in some cases of 7:3 to 5:5 and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.8:2 to 0.8:2, in some cases 1.6:2 to 1:2, even in some cases 1.4:2 to 1.1:2 and in some cases about 1.2:2. [0868] In some embodiments, the nanoparticles are lipoplexes comprising DOTAP and DOPE in a molar ratio of 10:0 to 1:9, in some cases 8:2 to 3:7, and in some cases of 7:3 to 5:5 and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.8:2 to 0.8:2, in some cases 1.6:2 to 1:2, in some cases 1.4:2 to 1.1:2 and in some cases about 1.2:2. [0869] In some embodiments, the nanoparticles are lipoplexes comprising DOTMA and DOPE in a molar ratio of 2:1 to 1:2, in some cases 2:1 to 1:1, and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.4:1 or less. WSGR Docket No.50401-795.601 [0870] In some embodiments, the nanoparticles are lipoplexes comprising DOTMA and cholesterol in a molar ratio of 2:1 to 1:2, in some cases 2:1 to 1:1, and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.4:1 or less. In some embodiments, the nanoparticles are lipoplexes comprising DOTAP and DOPE in a molar ratio of 2:1 to 1:2, in some cases 2:1 to 1:1, and wherein the charge ratio of positive charges in DOTAP to negative charges in the RNA is 1.4:1 or less. [0871] In some embodiments, the nanoparticles have an average diameter in the range of from about 50 nm to about 1000 nm, in some cases from about 50 nm to about 400 nm, in some cases about 100 nm to about 300 nm such as about 150 nm to about 200 nm. In some embodiments, the nanoparticles have a diameter in the range of about 200 to about 400 nm. [0872] In some embodiments, the polydispersity index of the nanoparticles described herein as measured by dynamic light scattering is 0.5 or less, in some cases 0.4 or less or in some cases 0.3 or less. [0873] In some embodiments, the nanoparticles described herein are obtainable by one or more of the following: (i) incubation of liposomes in an aqueous phase with the RNA in an aqueous phase, (ii) incubation of the lipid dissolved in an organic, water miscible solvent, such as ethanol, with the RNA in aqueous solution, (iii) reverse phase evaporation technique, (iv) freezing and thawing of the product, (v) dehydration and rehydration of the product, (vi) lyophilization and rehydration of the of the product, or (vii) spray drying and rehydration of the product. [0874] In some embodiments, the nanoparticles are produced by a process comprising a step of incubating the RNA with bivalent cations in some cases at a concentration of between 0.1 mM to 5 mM such as 0.1 mM to 4 mM or 0.3 mM to 1 mM prior to incorporation into said nanoparticles and/or by incubating the RNA with monovalent ions in some cases at a concentration of between 1 mM to 500 mM such as 100 mM to 200 mM or 130 mM to 170 mM prior to incorporation into said nanoparticles and/or by incubating the RNA with buffers prior to incorporation into said nanoparticles. [0875] In some embodiments, after incubation of the bivalent cations to RNA a step of dilution by adding liposomes and/or other aqueous phases by at least a factor of more than 1.5, in some cases by a factor of more than 2, or by a factor of more than 5 is involved. In some embodiments, the bivalent cations are calcium ions, where the final concentration of said calcium ions is less than 4 mM, in some cases less than 3 mM and in some cases 2.2 mM or less. [0876] In some embodiments, the nanoparticles described herein are produced by a process comprising a step of extruding and/or a step of filtration and/or a step of lyophilizing the nanoparticles. Vaccine Formulations WSGR Docket No.50401-795.601 [0877] In some embodiments, the present disclosure is directed to a vaccine formulation, e.g., a pharmaceutical composition capable of raising a neoantigen-specific response (e.g., a humoral or cell- mediated immune response). In some embodiments, the vaccine formulation comprises a RAS polypeptide or recombinant nucleic acid encoding a RAS polypeptide. In some embodiments, the vaccine formulation comprises an immune cell comprising the recombinant nucleic acid encoding the RAS polypeptide. [0878] In some embodiments, a vaccine formulation described herein is capable of raising a specific cytotoxic T cells response, specific helper T cell response, or a B cell response. In some embodiments, antigen polypeptides or polynucleotides can be provided as antigen presenting cells (e.g., dendritic cells) containing, for example, a RAS polypeptide or recombinant nucleic acid encoding a RAS polypeptide. In other embodiments, such antigen presenting cells are used to stimulate T cells for use in patients. In some embodiments, the antigen presenting cells are dendritic cells. In related embodiments, the dendritic cells are autologous dendritic cells that are pulsed with the neoantigen peptide or nucleic acid. The neoantigen peptide can be any suitable peptide that gives rise to an appropriate T cell response. In some embodiments, the T cell is a CTL. In some embodiments, the T cell is an HTL. Thus, one embodiment of the present disclosure is a vaccine formulation containing at least one antigen presenting cell (e.g., a dendritic cell) that is pulsed or loaded with one or more neoantigen polypeptides or polynucleotides described herein. In some embodiments, such APCs are autologous (e.g., autologous dendritic cells). Alternatively, peripheral blood mononuclear cells (PBMCs) isolated from a patient can be loaded with neoantigen peptides or polynucleotides ex vivo. In related embodiments, such APCs or PBMCs are injected back into the patient. The polynucleotide can be any suitable polynucleotide that is capable of transducing the dendritic cell, thus resulting in the presentation of a neoantigen peptide and induction of immunity. In some embodiments, such antigen presenting cells (APCs) (e.g., dendritic cells) or peripheral blood mononuclear cells (PBMCs) are used to stimulate a T cell (e.g., an autologous T cell). In related embodiments, the T cell is a CTL. In other related embodiments, the T cell is an HTL. In some embodiments, the T cells are CD8+ T cells. In some embodiments, the T cells are CD4+ T cells. Such T cells are then injected into the patient. In some embodiments, CTL is injected into the patient. In some embodiments, HTL is injected into the patient. In some embodiments, both CTL and HTL are injected into the patient. Administration of either therapeutic can be performed simultaneously or sequentially and in any order. [0879] In some embodiments, a RAS polypeptide or recombinant nucleic acids encoding a RAS polypeptide can be provided. The concentration of antigen polypeptides can vary widely, i.e., from less than about 0.1%, usually at or at least about 2% to as much as 20% to 50% or more by weight, WSGR Docket No.50401-795.601 and will be selected by fluid volumes, viscosities, etc., according to the particular mode of administration selected. [0880] In some embodiments, a vaccine formulation described herein for therapeutic treatment can be formulated for parenteral, topical, nasal, oral or local administration. In some embodiments, the vaccine formulation described herein are administered parenterally, e.g., intravenously, subcutaneously, intradermally, or intramuscularly. In some embodiments, the vaccine formulation can be administered intratumorally. The vaccine formulation can be administered at the site of surgical excision to induce a local immune response to the tumor. [0881] In some embodiments, described herein are compositions (e.g., vaccine formulations) for parenteral administration which comprise a solution of the neoantigen peptides and vaccine formulations are dissolved or suspended in an acceptable carrier, for example, an aqueous carrier. A variety of aqueous carriers can be used, e.g., water, buffered water, 0.9% saline, 0.3% glycine, hyaluronic acid and the like. These compositions can be sterilized by conventional, well known sterilization techniques, or can be sterile filtered. The resulting aqueous solutions can be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile solution prior to administration. The compositions can contain pharmaceutically acceptable auxiliary substances to approximate physiological conditions, such as pH adjusting and buffering agents, tonicity adjusting agents, wetting agents and the like, for example, sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate, triethanolamine oleate, etc. [0882] The ability of an adjuvant to increase the immune response to an antigen is typically manifested by a significant increase in immune-mediated reaction, or reduction in disease symptoms. For example, an increase in humoral immunity can be manifested by a significant increase in the titer of antibodies raised to the antigen, and an increase in T cell activity can be manifested in increased cell proliferation, or cellular cytotoxicity, or cytokine secretion. An adjuvant can also alter an immune response, for example, by changing a primarily humoral or T helper 2 response into a primarily cellular, or T helper 1 response. [0883] Suitable adjuvants are known in the art (see, WO 2015/095811) and include, but are not limited to poly(I:C), poly-ICLC, STING agonist, 1018 ISS, aluminum salts, Amplivax, AS15, BCG, CP-870,893, CpG7909, CyaA, dSLIM, GM-CSF, IC30, IC31, Imiquimod, ImuFact IMP321, IS Patch, ISS, ISCOMATRIX, JuvImmune, LipoVac, MF59, monophosphoryl lipid A, Montanide IMS 1312, Montanide ISA 206, Montanide ISA 50V, Montanide ISA-51, OK-432, OM-174, OM-197-MP- EC, ONTAK, PepTel® vector system, PLG microparticles, resiquimod, SRL172, virosomes and other virus-like particles, YF-17D, VEGF trap, R848, β-glucan, Pam3Cys, Pam3CSK4, Aquila’s QS21 stimulon (Aquila Biotech, Worcester, Mass., USA) which is derived from saponin, mycobacterial extracts and synthetic bacterial cell wall mimics, and other proprietary adjuvants such as Ribi’s WSGR Docket No.50401-795.601 Detox. Quil or Superfos. Several immunological adjuvants (e.g., MF59) specific for dendritic cells and their preparation have been described (Dupuis M, et al., Cell Immunol.1998; 186(1):18-27; Allison A C; Dev Biol Stand.1998; 92:3-11) (Mosca et al. Frontiers in Bioscience, 2007; 12:4050- 4060) (Gamvrellis et al. Immunol & Cell Biol.2004; 82: 506-516). Also, cytokines can be used. Several cytokines have been directly linked to influencing dendritic cell migration to lymphoid tissues (e.g., TNF-α), accelerating the maturation of dendritic cells into efficient antigen-presenting cells for T-lymphocytes (e.g., GM-CSF, PGE1, PGE2, IL-1, IL-1β, IL-4, IL-6 and CD40L) (U.S. Pat. No. 5,849,589 incorporated herein by reference in its entirety) and acting as immunoadjuvants (e.g., IL- 12) (Gabrilovich D I, et al., J Immunother Emphasis Tumor Immunol.1996 (6):414-418). [0884] CpG immunostimulatory oligonucleotides have also been reported to enhance the effects of adjuvants in a therapeutic setting. Without being bound by theory, CpG oligonucleotides act by activating the innate (non-adaptive) immune system via Toll-like receptors (TLR), mainly TLR9. CpG triggered TLR9 activation enhances antigen-specific humoral and cellular responses to a wide variety of antigens, including peptide or protein antigens, live or killed viruses, dendritic cell vaccine formulations, autologous cellular vaccine formulations and polysaccharide conjugates in both prophylactic and therapeutic vaccine formulations. Importantly, it enhances dendritic cell maturation and differentiation, resulting in enhanced activation of TH1 cells and strong cytotoxic T-lymphocyte (CTL) generation, even in the absence of CD4+ T cell help. The TH1 bias induced by TLR9 stimulation is maintained even in the presence of adjuvants such as alum or incomplete Freund’s adjuvant (IFA) that normally promote a TH2 bias. CpG oligonucleotides show even greater adjuvant activity when formulated or co-administered with other adjuvants or in formulations such as microparticles, nanoparticles, lipid emulsions or similar formulations, which are especially useful for inducing a strong response when the antigen is relatively weak. They can also accelerate the immune response and enabled the antigen doses to be reduced with comparable antibody responses to the full- dose vaccine formulation without CpG in some experiments (Arthur M. Krieg, Nature Reviews, Drug Discovery, 5, June 2006, 471-484). U.S. Pat. No.6,406,705 describes the combined use of CpG oligonucleotides, non-nucleic acid adjuvants and an antigen to induce an antigen-specific immune response. A commercially available CpG TLR9 antagonist is dSLIM (double Stem Loop Immunomodulator) by Mologen (Berlin, DE), which is a component of the pharmaceutical composition described herein. Other TLR binding molecules such as RNA binding TLR7, TLR8 and/or TLR9 can also be used. [0885] Other examples of useful adjuvants include, but are not limited to, chemically modified CpGs (e.g. CpR, Idera), Poly(I and/or poly C)(e.g., polyI:CI2U), non-CpG bacterial DNA or RNA, ssRNA40 for TLR8, as well as immunoactive small molecules and antibodies such as cyclophosphamide, sunitinib, bevacizumab, celebrex, NCX-4016, sildenafil, tadalafil, vardenafil, WSGR Docket No.50401-795.601 sorafinib, XL-999, CP-547632, pazopanib, ZD2171, AZD2171, ipilimumab, tremelimumab, and SC58175, which can act therapeutically and/or as an adjuvant. The amounts and concentrations of adjuvants and additives useful in the context of the present disclosure can readily be determined by the skilled artisan without undue experimentation. Additional adjuvants include colony-stimulating factors, such as Granulocyte Macrophage Colony Stimulating Factor (GM-CSF, sargramostim). [0886] In some embodiments, a vaccine formulation according to the present disclosure can comprise more than one different adjuvant. Furthermore, the present disclosure encompasses a pharmaceutical composition comprising any adjuvant substance including any of the above or combinations thereof. In some embodiments, the vaccine formulation comprises a RAS polypeptide or recombinant nucleic acid encoding a RAS polypeptide. In some embodiments, the vaccine formulation comprises an immune cell comprising the recombinant nucleic acid encoding the RAS polypeptide. In some cases, the adjuvant can be administered separately in any appropriate sequence. [0887] Lipidation can be classified into several different types, such as N-myristoylation, palmitoylation, GPI-anchor addition, prenylation, and several additional types of modifications. N- myristoylation is the covalent attachment of myristate, a C14 saturated acid, to a glycine residue. Palmitoylation is thioester linkage of long-chain fatty acids (C16) to cysteine residues. GPI-anchor addition is glycosyl-phosphatidylinositol (GPI) linkage via amide bond. Prenylation is the thioether linkage of an isoprenoid lipid (e.g., farnesyl (C-15), geranylgeranyl (C-20)) to cysteine residues. Additional types of modifications can include attachment of S-diacylglycerol by a sulfur atom of cysteines, O-octanoyl conjugation via serine or threonine residues, S-archaeol conjugation to cysteine residues, and cholesterol attachment. [0888] Fatty acids for generating lipidated peptides can include C2 to C30 saturated, monounsaturated, or polyunsaturated fatty acyl groups. Exemplary fatty acids can include palmitoyl, myristoyl, stearoyl and decanoyl groups. In some instances, a lipid moiety that has adjuvant property is attached to a polypeptide of interest to elicit or enhance immunogenicity in the absence of an extrinsic adjuvant. A lipidated peptide or lipopeptide can be referred to as a self-adjuvant lipopeptide. Any of the fatty acids described above and elsewhere herein can elicit or enhance immunogenicity of a polypeptide of interest. A fatty acid that can elicit or enhance immunogenicity can include palmitoyl, myristoyl, stearoyl, lauroyl, octanoyl, and decanoyl groups. [0889] Polypeptides such as naked peptides or lipidated peptides can be incorporated into a liposome. Sometimes, lipidated peptides can be incorporated into a liposome. For example, the lipid portion of the lipidated peptide can spontaneously integrate into the lipid bilayer of a liposome. Thus, a lipopeptide can be presented on the “surface” of a liposome. Exemplary liposomes suitable for incorporation in the formulations include, and are not limited to, multilamellar vesicles (MLV), oligolamellar vesicles (OLV), unilamellar vesicles (UV), small unilamellar vesicles (SUV), medium- WSGR Docket No.50401-795.601 sized unilamellar vesicles (MUV), large unilamellar vesicles (LUV), giant unilamellar vesicles (GUV), multivesicular vesicles (MVV), single or oligolamellar vesicles made by reverse-phase evaporation method (REV), multilamellar vesicles made by the reverse-phase evaporation method (MLV-REV), stable plurilamellar vesicles (SPLV), frozen and thawed MLV (FATMLV), vesicles prepared by extrusion methods (VET), vesicles prepared by French press (FPV), vesicles prepared by fusion (FUV), dehydration-rehydration vesicles (DRV), and bubblesomes (BSV). [0890] The RAS polypeptide and recombinant nucleic acids described herein can also be administered via liposomes, which target the peptides to a particular cells tissue, such as lymphoid tissue. Liposomes are also useful in increasing the half-life of the peptides. Liposomes include emulsions, foams, micelles, insoluble monolayers, liquid crystals, phospholipid dispersions, lamellar layers and the like. In these preparations the peptide to be delivered is incorporated as part of a liposome, alone or in conjunction with a molecule which binds to, e.g., a receptor prevalent among lymphoid cells, such as monoclonal antibodies which bind to the DEC205 antigen, or with other therapeutic or vaccine formulations. Thus, liposomes filled with a desired peptide or polynucleotide described herein can be directed to the site of lymphoid cells, where the liposomes then deliver the selected therapeutic/immunogenic polypeptide/polynucleotide compositions. Liposomes can be formed from standard vesicle-forming lipids, which generally include neutral and negatively charged phospholipids and a sterol, for example, cholesterol. The selection of lipids is generally guided by consideration of, e.g., liposome size, acid lability and stability of the liposomes in the blood stream. A variety of methods are available for preparing liposomes, as described in, e.g., Szoka et al., Ann. Rev. Biophys. Bioeng.9; 467 (1980), U.S. Pat. Nos.4,235,871, 4,501,728, 4,501,728, 4,837,028, and 5,019,369. [0891] For targeting to the immune cells, a RAS polypeptide or recombinant nucleic acid to be incorporated into the liposome for cell surface determinants of the desired immune system cells. A liposome suspension containing a peptide can be administered intravenously, locally, topically, etc. in a dose which varies according to, inter alia, the manner of administration, the polypeptide or recombinant nucleic acid being delivered, and the stage of the disease being treated. [0892] In some embodiments, the RAS polypeptide and recombinant nucleic acids are targeted to dendritic cells. In some embodiments, the RAS polypeptide and recombinant nucleic acids are target to dendritic cells using the markers DEC205, XCR1, CD197, CD80, CD86, CD123, CD209, CD273, CD283, CD289, CD184, CD85h, CD85j, CD85k, CD85d, CD85g, CD85a, TSLP receptor, or CD1a. [0893] For solid compositions, conventional or nanoparticle nontoxic solid carriers can be used which include, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, magnesium carbonate, and the like. For oral administration, a pharmaceutically acceptable nontoxic composition is formed by incorporating any of WSGR Docket No.50401-795.601 the normally employed excipients, such as those carriers previously listed, and generally 10-95% of active ingredient, that is, one or more RAS polypeptides and recombinant nucleic acids described herein at a concentration of 25%-75%. [0894] For aerosol administration, the RAS polypeptide and recombinant nucleic acids can be supplied in finely divided form along with a surfactant and propellant. Representative of such agents are the esters or partial esters of fatty acids containing from 6 to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic, stearic, linoleic, linolenic, olesteric and oleic acids with an aliphatic polyhydric alcohol or its cyclic anhydride. Mixed esters, such as mixed or natural glycerides can be employed. The surfactant can constitute 0.1%-20% by weight of the composition, or 0.25-5%. The balance of the composition can be propellant. A carrier can also be included as desired, as with, e.g., lecithin for intranasal delivery. [0895] Additional methods for delivering the recombinant nucleic acids described herein are also known in the art. For instance, the nucleic acid can be delivered directly, as “naked DNA”. This approach is described, for instance, in Wolff et al., Science 247: 1465-1468 (1990) as well as U.S. Pat. Nos.5,580,859 and 5,589,466. The nucleic acids can also be administered using ballistic delivery as described, for instance, in U.S. Pat. No.5,204,253. Particles comprised solely of DNA can be administered. Alternatively, DNA can be adhered to particles, such as gold particles. [0896] For therapeutic or immunization purposes, DNA or RNA encoding the RAS polypeptide can also be administered to the subject. In some embodiments the recombinant nucleic acids encoding the RAS polypeptide may be part of a synthetic lipid nanoparticle formulation. In some embodiments, the recombinant nucleic acid is DNA. In some embodiments, the recombinant nucleic acid is mRNA. [0897] The recombinant nucleic acids can also be delivered complexed to cationic compounds, such as cationic lipids. In some embodiments, nucleic acids can be encapsulated in lipid nanoparticles (e.g., comprising cationic lipid, non-cationic lipids (e.g., phospholipids and/or sterol), and/or PEG-lipids). Lipid-mediated gene delivery methods are described, for instance, in WO 96/18372, WO 93/24640; Mannino & Gould-Fogerite, BioTechniques 6(7): 682-691 (1988); U.S. Pat. No.5,279,833; WO 91/06309; and Feigner et al., Proc. Natl. Acad. Sci. USA 84: 7413-7414 (1987). [0898] Depending on the method of preparation, liposomes can be unilamellar or multilamellar, and can vary in size with diameters ranging from about 0.02 μM to greater than about 10 μm. Liposomes can adsorb many types of cells and then release an incorporated agent (e.g., a peptide described herein). In some cases, the liposomes fuse with the target cell, whereby the contents of the liposome then empty into the target cell. A liposome can be endocytosed by cells that are phagocytic. Endocytosis can be followed by intralysosomal degradation of liposomal lipids and release of the encapsulated agents. WSGR Docket No.50401-795.601 [0899] The liposomes provided herein can also comprise carrier lipids. In some embodiments the carrier lipids are phospholipids. Carrier lipids capable of forming liposomes include, but are not limited to dipalmitoylphosphatidylcholine (DPPC), phosphatidylcholine (PC; lecithin), phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylserine (PS). Other suitable phospholipids further include distearoylphosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidyglycerol (DPPG), distearoylphosphatidyglycerol (DSPG), dimyristoylphosphatidylglycerol (DMPG), dipalmitoylphosphatidic acid (DPPA); dimyristoylphosphatidic acid (DMPA), distearoylphosphatidic acid (DSPA), dipalmitoylphosphatidylserine (DPPS), dimyristoylphosphatidylserine (DMPS), distearoylphosphatidylserine (DSPS), dipalmitoylphosphatidyethanolamine (DPPE), dimyristoylphosphatidylethanolamine (DMPE), distearoylphosphatidylethanolamine (DSPE) and the like, or combinations thereof. In some embodiments, the liposomes further comprise a sterol (e.g., cholesterol) which modulates liposome formation. The carrier lipids can be any known non-phosphate polar lipids. [0900] Cell-based vaccine formulations can also be administered to a subject. For example, an antigen presenting cell (APC) based vaccine formulation can be formulated using any of the well- known techniques, carriers, and excipients as suitable and as understood in the art. APCs include monocytes, monocyte-derived cells, macrophages, and dendritic cells. Sometimes, an APC based vaccine formulation can be a dendritic cell-based vaccine formulation. [0901] A dendritic cell-based vaccine formulation can be prepared by any methods well known in the art. In some cases, dendritic cell-based vaccine formulations can be prepared through an ex vivo or in vivo method. The ex vivo method can comprise the use of autologous DCs pulsed ex vivo with the polypeptides described herein, to activate or load the DCs prior to administration into the patient. The in vivo method can comprise targeting specific DC receptors using antibodies coupled with the polypeptides described herein. The DC-based vaccine formulation can further comprise DC activators such as TLR3, TLR-7-8, and CD40 agonists. The DC-based vaccine formulation can further comprise adjuvants, and a pharmaceutically acceptable carrier. [0902] An adjuvant can be used to enhance the immune response (humoral and/or cellular) elicited in a patient receiving the vaccine formulation. Sometimes, adjuvants can elicit a Th1-type response. Other times, adjuvants can elicit a Th2-type response. A Th1-type response can be characterized by the production of cytokines such as IFN-γ as opposed to a Th2-type response which can be characterized by the production of cytokines such as IL-4, IL-5 and IL-10. [0903] In some aspects, lipid-based adjuvants, such as MPLA and MDP, can be used with the vaccine formulations disclosed herein. Monophosphoryl lipid A (MPLA), for example, is an adjuvant that causes increased presentation of liposomal antigen to specific T Lymphocytes. In addition, a WSGR Docket No.50401-795.601 muramyl dipeptide (MDP) can also be used as a suitable adjuvant in conjunction with the immunogenic pharmaceutical formulations described herein. [0904] Adjuvant can also comprise stimulatory molecules such as cytokines. Non-limiting examples of cytokines include: CCL20, α-interferon (IFNα), β-interferon (IFNβ), γ-interferon (IFNγ), platelet derived growth factor (PDGF), TNFα, GM-CSF, epidermal growth factor (EGF), cutaneous T cell- attracting chemokine (CTACK), epithelial thymus-expressed chemokine (TECK), mucosae-associated epithelial chemokine (MEC), IL-12, IL-15, IL-28, MHC, CD80, CD86, IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-18, MCP-1, MIP-la, MIP-1-, IL-8, L- selectin, P-selectin, E-selectin, CD34, GlyCAM-1, MadCAM-1, LFA-1, VLA-1, Mac-1, pl50.95, PECAM, ICAM-1, ICAM-2, ICAM-3, CD2, LFA-3, M-CSF, G-CSF, mutant forms of IL-18, CD40, CD40L, vascular growth factor, fibroblast growth factor, IL-7, nerve growth factor, vascular endothelial growth factor, Fas, TNF receptor, Fit, Apo-1, p55, WSL-1, DR3, TRAMP, Apo-3, AIR, LARD, NGRF, DR4, DRS, KILLER, TRAIL-R2, TRICK2, DR6, Caspase ICE, Fos, c-jun, Sp-1, Ap-1, Ap-2, p38, p65Rel, MyD88, IRAK, TRAF6, IκB, Inactive NIK, SAP K, SAP-I, JNK, interferon response genes, NFκB, Bax, TRAIL, TRAILrec, TRAILrecDRC5, TRAIL-R3, TRAIL-R4, RANK, RANK LIGAND, Ox40, Ox40 LIGAND, NKG2D, MICA, MICB, NKG2A, NKG2B, NKG2C, NKG2E, NKG2F, TAPI, and TAP2. [0905] Additional adjuvants include: MCP-1, MIP-la, MIP-lp, IL-8, RANTES, L-selectin, P-selectin, E-selectin, CD34, GlyCAM-1, MadCAM-1, LFA-1, VLA-1, Mac-1, pl50.95, PECAM, ICAM-1, ICAM-2, ICAM-3, CD2, LFA-3, M-CSF, G-CSF, IL-4, mutant forms of IL-18, CD40, CD40L, vascular growth factor, fibroblast growth factor, IL-7, IL-22, nerve growth factor, vascular endothelial growth factor, Fas, TNF receptor, Fit, Apo-1, p55, WSL-1, DR3, TRAMP, Apo-3, AIR, LARD, NGRF, DR4, DR5, KILLER, TRAIL-R2, TRICK2, DR6, Caspase ICE, Fos, c-jun, Sp-1, Ap-1, Ap-2, p38, p65Rel, MyD88, IRAK, TRAF6, IκB, Inactive NIK, SAP K, SAP-1, JNK, interferon response genes, NFκB, Bax, TRAIL, TRAILrec, TRAILrecDRC5, TRAIL-R3, TRAIL-R4, RANK, RANK LIGAND, Ox40, Ox40 LIGAND, NKG2D, MICA, MICB, NKG2A, NKG2B, NKG2C, NKG2E, NKG2F, TAP1, TAP2 and functional fragments thereof. [0906] In some aspects, an adjuvant can be a modulator of a toll like receptor. Examples of modulators of toll-like receptors include TLR9 agonists and are not limited to small molecule modulators of toll-like receptors such as Imiquimod. Sometimes, an adjuvant is selected from bacteria toxoids, polyoxypropylene-polyoxyethylene block polymers, aluminum salts, liposomes, CpG polymers, oil-in-water emulsions, or a combination thereof. Sometimes, an adjuvant is an oil-in-water emulsion. The oil-in-water emulsion can include at least one oil and at least one surfactant, with the oil(s) and surfactant(s) being biodegradable (metabolizable) and biocompatible. The oil droplets in the emulsion can be less than 5 μm in diameter, and can even have a sub-micron diameter, with these WSGR Docket No.50401-795.601 small sizes being achieved with a microfluidiser to provide stable emulsions. Droplets with a size less than 220 nm can be subjected to filter sterilization. [0907] In some instances, a vaccine formulation can include carriers and excipients (including but not limited to buffers, carbohydrates, mannitol, proteins, polypeptides or amino acids such as glycine, antioxidants, bacteriostats, chelating agents, suspending agents, thickening agents and/or preservatives), water, oils including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like, saline solutions, aqueous dextrose and glycerol solutions, flavoring agents, coloring agents, detackifiers and other acceptable additives, adjuvants, or binders, other pharmaceutically acceptable auxiliary substances to approximate physiological conditions, such as pH buffering agents, tonicity adjusting agents, emulsifying agents, wetting agents and the like. Examples of excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. In another instances, the pharmaceutical preparation is substantially free of preservatives. In other instances, the pharmaceutical preparation can contain at least one preservative. It will be recognized that, while any suitable carrier known to those of ordinary skill in the art can be employed to administer the pharmaceutical compositions described herein, the type of carrier will vary depending on the mode of administration. [0908] A vaccine formulation can include preservatives such as thiomersal or 2-phenoxyethanol. In some instances, the vaccine formulation is substantially free from (e.g., <10 μg/mL) mercurial material e.g., thiomersal-free. α-Tocopherol succinate may be used as an alternative to mercurial compounds. [0909] For controlling the tonicity, a physiological salt such as sodium salt can be included in the vaccine formulation. Other salts can include potassium chloride, potassium dihydrogen phosphate, disodium phosphate, and/or magnesium chloride, or the like. [0910] A vaccine formulation can have an osmolality of between 200 mOsm/kg and 400 mOsm/kg, between 240-360 mOsm/kg, or within the range of 290-310 mOsm/kg. [0911] A vaccine formulation can comprise one or more buffers, such as a Tris buffer; a borate buffer; a succinate buffer; a histidine buffer (particularly with an aluminum hydroxide adjuvant); or a citrate buffer. Buffers, in some cases, are included in the 5-20 or 10-50 mM range. [0912] The pH of the vaccine formulation can be between about 5.0 and about 8.5, between about 6.0 and about 8.0, between about 6.5 and about 7.5, or between about 7.0 and about 7.8. [0913] A vaccine formulation can be sterile. The vaccine formulation can be non-pyrogenic e.g., containing <1 EU (endotoxin unit, a standard measure) per dose, and can be <0.1 EU per dose. The composition can be gluten free. WSGR Docket No.50401-795.601 [0914] A vaccine formulation can include detergent e.g., a polyoxyethylene sorbitan ester surfactant (known as ‘Tweens’), or an octoxynol (such as octoxynol-9 (Triton X-100) or t- octylphenoxypolyethoxyethanol). The detergent can be present only at trace amounts. The vaccine formulation can include less than 1 mg/mL of each of octoxynol-10 and polysorbate 80. Other residual components in trace amounts can be antibiotics (e.g., neomycin, kanamycin, polymyxin B). [0915] A vaccine formulation can be formulated as a sterile solution or suspension, in suitable vehicles, well known in the art. The pharmaceutical compositions can be sterilized by conventional, well-known sterilization techniques, or can be sterile filtered. The resulting aqueous solutions can be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile solution prior to administration. [0916] In some instances, a vaccine formulation can be administered with an additional agent. The choice of the additional agent can depend, at least in part, on the condition being treated. The additional agent can include, for example, a checkpoint inhibitor agent such as an anti-PD1, anti- CTLA4, anti-PD-L1, anti CD40, or anti-TIM3 agent (e.g., an anti-PD1, anti-CTLA4, anti-PD-L1, anti CD40, or anti-TIM3 antibody); or any agents having a therapeutic effect for a pathogen infection (e.g. viral infection), including, e.g., drugs used to treat inflammatory conditions such as an NSAID, e.g., ibuprofen, naproxen, acetaminophen, ketoprofen, or aspirin. For example, the checkpoint inhibitor can be a PD-1/PD- L1 antagonist selected from the group consisting of: nivolumab (ONO-4538/BMS- 936558, MDX1106, OPDIVO), pembrolizumab (MK-3475, KEYTRUDA), pidilizumab (CT-011), and MPDL328OA (ROCHE). As another example, formulations can additionally contain one or more supplements, such as vitamin C, E or other anti-oxidants. [0917] In some embodiments, the vaccine formulation comprises a nanoparticle. For example, the vaccine described herein (e.g., RAS vaccine) can be embedded or encapsulated within the nanoparticle. In some embodiments, the nanoparticle is a lipid nanoparticle or a liposome. In some embodiments, the particle is a lipoplex. The term, “lipoplex,” can refer to a complex of lipids and nucleic acids such as RNA. Lipoplexes can be formed spontaneously when cationic liposomes, which often also include a neutral “helper” lipid, are mixed with nucleic acids. In some embodiments, the lipid is comprised in a vesicle encapsulating the RNA. The vesicle may be a multilamellar vesicle, an unilamellar vesicle, or a mixture thereof. The vesicle may be a liposome. [0918] In some embodiments, the nanoparticulate RNA formulations with defined particle size are provided wherein the net charge of the particles is close to zero or negative. In some embodiments, the RNA nanoparticles are RNA lipoplexes. A strong immune response against a model antigen can be induced. [0919] The lipoplexes can have a well-defined particle size distribution profile as measured by dynamic light scattering and with low fraction of subvisible particles, which may be needed for WSGR Docket No.50401-795.601 intravenous administration to patients. If formed by incubation of liposomes with RNA by self- assembly, the particle size of the original liposomes may not be affected, and no undesired moieties of large aggregates can be found. Different sizes can be obtained by selecting the size of the precursor liposomes and the mixing conditions. The particles can be frozen and thawed without formation of aggregates, while maintaining the original particle size profile, and maintaining the biological activity. The particles can be lyophilized and reconstituted with water without formation of aggregates, while maintaining the original particle size profile and maintaining the biological activity. The particles can be manufactured by different protocols which are scalable and which can be performed under controlled conditions. With such properties the lipoplex formulations of the present disclosure can fulfill important requirements for pharmaceutical formulations for application to patients, in terms of particle size distribution profile and stability. Furthermore, compared to positively charged lipopexes, the RNA nanoparticles described herein can be less toxic and to display less undesired serum interactions. In particular, the formulations can be suitable for parenteral administration, including intravenous and subcutaneous administration. [0920] In some embodiments, the nanoparticles are lipoplexes comprising DOTMA and DOPE in a molar ratio of 10:0 to 1:9, in some cases 8:2 to 3:7, and in some cases of 7:3 to 5:5 and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.8:2 to 0.8:2, in some cases 1.6:2 to 1:2, in some cases 1.4:2 to 1.1:2 and in some cases about 1.2:2. In some embodiments, the nanoparticles are lipoplexes comprising DOTMA and Cholesterol in a molar ratio of 10:0 to 1 :9, in some cases 8:2 to 3:7, and in some cases of 7:3 to 5:5 and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.8:2 to 0.8:2, in some cases 1.6:2 to 1:2, in some cases 1.4:2 to 1.1:2 and in some cases about 1.2:2. In some embodiments, the nanoparticles are lipoplexes comprising DOTAP and DOPE in a molar ratio of 10:0 to 1:9, in some cases 8:2 to 3:7, and in some cases of 7:3 to 5:5 and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.8:2 to 0.8:2, in some cases 1.6:2 to 1:2, in some cases 1.4:2 to 1.1:2 and in some cases about 1.2:2. In some embodiments, the nanoparticles are lipoplexes comprising DOTMA and DOPE in a molar ratio of 2:1 to 1:2, in some cases 2:1 to 1:1, and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.4:1 or less. In some embodiments, the nanoparticles are lipoplexes comprising DOTMA and cholesterol in a molar ratio of 2:1 to 1:2, in some cases 2:1 to 1:1, and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.4:1 or less. In some embodiments, the nanoparticles are lipoplexes comprising DOTAP and DOPE in a molar ratio of 2:1 to 1:2, in some cases 2: to 1:1, and wherein the charge ratio of positive charges in DOTAP to negative charges in the RNA is 1.4:1 or less. In some embodiments, the nanoparticles have an average diameter in the range of from about 50 nm to about 1000 nm, in some cases from about 50 nm to about 400 nm, in some cases about 100 nm to about 300 WSGR Docket No.50401-795.601 nm such as about 150 nm to about 200 nm. In some embodiments, the nanoparticles have a diameter in the range of about 200 to about 400 nm. In some embodiments, the polydispersity index of the nanoparticles described herein as measured by dynamic light scattering is 0.5 or less, in some cases 0.4 or less or in some cases 0.3 or less. [0921] In some embodiments, the nanoparticles described herein are obtainable by one or more of the following: (i) incubation of liposomes in an aqueous phase with the RNA in an aqueous phase, (ii) incubation of the lipid dissolved in an organic, water miscible solvent, such as ethanol, with the RNA in aqueous solution, (iii) reverse phase evaporation technique, (iv) freezing and thawing of the product, (v) dehydration and rehydration of the product, (vi) lyophilization and rehydration of the of the product, or (vii) spray drying and rehydration of the product. [0922] In some embodiments, the lipid solutions, liposomes and RNA lipoplex particles described herein include a cationic lipid. As used herein, a "cationic lipid" refers to a lipid having a net positive charge. Cationic lipids bind negatively charged RNA by electrostatic interaction to the lipid matrix. Generally, cationic lipids possess a lipophilic moiety, such as a sterol, an acyl or diacyl chain, and the head group of the lipid typically carries the positive charge. Examples of cationic lipids include, but are not limited to l,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA), dimethyldioctadecylammonium (DDAB); l,2-dioleoyl-3 -trimethylammonium propane (DOTAP); l,2- dioleoyl-3-dimethylammonium-propane (DODAP); l,2-diacyloxy-3- dimethylammonium propanes; l,2-dialkyloxy-3- dimethylammonium propanes; dioctadecyldimethyl ammonium chloride (DODAC), 2,3-di(tetradecoxy)propyl-(2- hydroxyethyl)-dimethylazanium (DMRIE), 1 ,2-dimyristoyl-sn-glycero- 3-ethylphosphocholine (DMEPC), l,2-dimyristoyl-3-trimethylammonium propane (DMTAP), l,2- dioleyloxypropyl-3- dimethyl-hydroxyethyl ammonium bromide (DORIE), and 2,3-dioleoyloxy- N- [2(spermine carboxamide)ethyl]-N,N-dimethyl-l-propanamium trifluoroacetate (DOSPA). Preferred are DOTMA, DOTAP, DODAC, and DOSPA. In specific embodiments, the at least one cationic lipid is DOTMA and/or DOTAP. In some embodiments, the at least one cationic lipid is DOTMA, in particular (R)-DOTMA. [0923] An additional lipid may be incorporated to adjust the overall positive to negative charge ratio and physical stability of the RNA lipoplex particles. In certain embodiments, the additional lipid is a neutral lipid. As used herein, a "neutral lipid" refers to a lipid having a net charge of zero. Examples of neutral lipids include, but are not limited to, l,2-di-(9Z-octadecenoyl)-sn- glycero-3- phosphoethanolamine (DOPE), 1 ,2-dioleoyl-sn-glycero-3 -phosphocholine (DOPC), diacylphosphatidyl choline, diacylphosphatidyl ethanol amine, ceramide, sphingoemyelin, cephalin, cholesterol, and cerebroside. In specific embodiments, the second lipid is DOPE, cholesterol and/or DOPC. WSGR Docket No.50401-795.601 [0924] In some embodiments, the RNA lipoplex particles include both a cationic lipid and an additional lipid. In some embodiments, the cationic lipid is DOTMA and the additional lipid is DOPE. Without wishing to be bound by theory, the amount of the at least one cationic lipid compared to the amount of the at least one additional lipid may affect important RNA lipoplex particle characteristics, such as charge, particle size, stability, tissue selectivity, and bioactivity of the RNA. Accordingly, in some embodiments, the molar ratio of the at least one cationic lipid to the at least one additional lipid is from about 10:0 to about 1 :9, about 4:1 to about 1 :2, or about 3 : 1 to about 1 : 1. In some embodiments, the molar ratio may be about 3:1, about 2.75:1, about 2.5:1, about 2.25:1, about 2:1, about 1.75:1, about 1.5: 1, about 1.25:1, or about 1 : 1. In some embodiments, the molar ratio of the at least one cationic lipid to the at least one additional lipid is about 2:1. RNA Lipoplex Particles [0925] Vaccine formulations may comprise RNA lipoplex particles described herein. According to the present disclosure, the compositions described herein may comprise salts such as sodium chloride. Without wishing to be bound by theory, sodium chloride functions as an ionic osmolality agent for preconditioning RNA prior to mixing with the at least one cationic lipid. Certain embodiments contemplate alternative organic or inorganic salts to sodium chloride in the present disclosure. Alternative salts include, without limitation, potassium chloride, dipotassium phosphate, monopotassium phosphate, potassium acetate, potassium bicarbonate, potassium sulfate, potassium acetate, disodium phosphate, monosodium phosphate, sodium acetate, sodium bicarbonate, sodium sulfate, sodium acetate, lithium chloride, magnesium chloride, magnesium phosphate, calcium chloride, and sodium salts of ethyl enediaminetetraacetic acid (EDTA). [0926] Generally, compositions comprising RNA lipoplex particles described herein comprise sodium chloride at a concentration that preferably ranges from 0 mM to about 500 mM, from about 5 mM to about 400 mM, or from about 10 mM to about 300 mM. In some embodiments, compositions comprising RNA lipoplex particles comprise an ionic strength corresponding to such sodium chloride concentrations. [0927] Generally, compositions for and resulting from forming RNA lipoplex particles from RNA and liposomes such as those described herein comprise high sodium chloride concentrations, or comprises a high ionic strength. In some embodiments, the sodium chloride is at a concentration of at least 45 mM. In some embodiments, the sodium chloride is at a concentration of about 45 mM to about 300 mM, or from about 50 mM to about 150 mM. In some embodiments, the compositions comprise an ionic strength corresponding to such sodium chloride concentrations. [0928] Generally, compositions for storing RNA lipoplex particles such as for freezing of RNA lipoplex particles such as those described herein comprise low sodium chloride concentrations, or comprises a low ionic strength. In some embodiments, the sodium chloride is at a concentration from WSGR Docket No.50401-795.601 0 mM to about 50 mM, from 0 mM to about 40 mM, or from about 10 mM to about 50 mM. In specific embodiments, the sodium chloride is at a concentration of about 1 mM, about 2 mM, about 3 mM, about 4 mM, about 5 mM, about 6 mM, about 7 mM, about 8 mM, about 9 mM, about 10 mM, about 11 mM, about 12 mM, about 13 mM, about 14 mM, about 15 mM, about 16 mM, about 17 mM, about 18 mM, about 19 mM, about 20 mM, about 21 mM, about 22 mM, about 23 mM, about 24 mM, about 25 mM, about 26 mM, about 27 mM, about 28 mM, about 29 mM, about 30 mM, about 31 mM, about 32 mM, about 33 mM, about 34 mM, about 35 mM, about 36 mM, about 37 mM, about 38 mM, about 39 mM, about 40 mM, about 41 mM, about 42 mM, about 43 mM, about 44 mM, about 45 mM, about 46 mM, about 47 mM, about 48 mM, about 49 mM, or about 50 mM. In some embodiments, the sodium chloride is at a concentration of about 20 mM, about 30 mM, or about 40 mM. In some embodiments, the sodium chloride is at a concentration of 20 mM. In some embodiments, the sodium chloride is at a concentration of 30 mM. In some embodiments, the compositions comprise an ionic strength corresponding to such sodium chloride concentrations. [0929] Generally, compositions resulting from thawing frozen RNA lipoplex particle compositions and optionally adjusting the osmolality and ionic strength by adding an aqueous liquid comprise high sodium chloride concentrations, or comprises a high ionic strength. In some embodiments, the sodium chloride is at a concentration of about 50 mM to about 300 mM, or from about 80 mM to about 150 mM. In some embodiments, the compositions comprise an ionic strength corresponding to such sodium chloride concentrations. [0930] Compositions described herein may comprise a stabilizer to avoid substantial loss of the product quality and, in particular, substantial loss of RNA activity during freezing, lyophilization or spray-drying and storage of the frozen, lyophilized or spray-dried composition. Such a composition is also referred to as stable herein. Typically the stabilizer is present prior to the freezing, lyophilization or spray-drying process and persists in the resulting frozen, lyophilized or freeze-dried preparation. It can be used to protect RNA lipoplex particles during freezing, lyophilization or spray-drying and storage of the frozen, lyophilized or freeze-dried preparation, for example to reduce or prevent aggregation, particle collapse, RNA degradation and/or other types of damage. [0931] In some embodiments, the stabilizer is a carbohydrate. The term "carbohydrate", as used herein refers to and encompasses monosaccharides, disaccharides, trisaccharides, oligosaccharides and polysaccharides. [0932] In some embodiments, the stabilizer is a monosaccharide. The term "monosaccharide", as used herein refers to a single carbohydrate unit (e.g., a simple sugar) that cannot be hydrolyzed to simpler carbohydrate units. Exemplary monosaccharide stabilizers include glucose, fructose, galactose, xylose, ribose and the like. WSGR Docket No.50401-795.601 [0933] In some embodiments, the stabilizer is a disaccharide. The term "disaccharide", as used herein refers to a compound or a chemical moiety formed by 2 monosaccharide units that are bonded together through a glycosidic linkage, for example through 1-4 linkages or 1-6 linkages. A disaccharide may be hydrolyzed into two monosaccharides. Exemplary disaccharide stabilizers include sucrose, trehalose, lactose, maltose and the like. The term "trisaccharide" means three sugars linked together to form one molecule. Examples of a trisaccharides include raffinose and melezitose. [0934] In some embodiments, the stabilizer is an oligosaccharide. The term "oligosaccharide", as used herein refers to a compound or a chemical moiety formed by 3 to about 15, preferably 3 to about 10 monosaccharide units that are bonded together through glycosidic linkages, for example through 1- 4 linkages or 1-6 linkages, to form a linear, branched or cyclic structure. Exemplary oligosaccharide stabilizers include cyclodextrins, raffinose, melezitose, maltotriose, stachyose, acarbose, and the like. An oligosaccharide can be oxidized or reduced. In some embodiments, the stabilizer is a cyclic oligosaccharide. The term "cyclic oligosaccharide", as used herein refers to a compound or a chemical moiety formed by 3 to about 15, preferably 6, 7, 8, 9, or 10 monosaccharide units that are bonded together through glycosidic linkages, for example through 1-4 linkages or 1-6 linkages, to form a cyclic structure. Exemplary cyclic oligosaccharide stabilizers include cyclic oligosaccharides that are discrete compounds, such as a cyclodextrin, b cyclodextrin, or g cyclodextrin. [0935] Other exemplary cyclic oligosaccharide stabilizers include compounds which include a cyclodextrin moiety in a larger molecular structure, such as a polymer that contains a cyclic oligosaccharide moiety. A cyclic oligosaccharide can be oxidized or reduced, for example, oxidized to dicarbonyl forms. The term "cyclodextrin moiety", as used herein refers to cyclodextrin (e.g., an a, b, or g cyclodextrin) radical that is incorporated into, or a part of, a larger molecular structure, such as a polymer. A cyclodextrin moiety can be bonded to one or more other moieties directly, or through an optional linker. A cyclodextrin moiety can be oxidized or reduced, for example, oxidized to dicarbonyl forms. [0936] Carbohydrate stabilizers, e.g., cyclic oligosaccharide stabilizers, can be derivatized carbohydrates. For example, in some embodiments, the stabilizer is a derivatized cyclic oligosaccharide, e.g., a derivatized cyclodextrin, e.g., 2-hydroxypropyl^-cyclodextrin, e.g., partially etherified cyclodextrins (e.g., partially etherified b cyclodextrins). [0937] An exemplary stabilizer is a polysaccharide. The term "polysaccharide", as used herein refers to a compound or a chemical moiety formed by at least 16 monosaccharide units that are bonded together through glycosidic linkages, for example through 1-4 linkages or 1-6 linkages, to form a linear, branched or cyclic structure, and includes polymers that comprise polysaccharides as part of their backbone structure. In backbones, the polysaccharide can be linear or cyclic. Exemplary polysaccharide stabilizers include glycogen, amylase, cellulose, dextran, maltodextrin and the like. In WSGR Docket No.50401-795.601 some embodiments, the stabilizer is a sugar alcohol. As used herein, the term "sugar alcohol" refers to reduction products of "sugars" and indicates that all oxygen atoms in a simple sugar alcohol molecule are present in the form of hydroxyl groups. The sugar alcohols are "polyols". This term refers to chemical compounds containing three or more hydroxyl groups, and is synonymous with another customary term, polyhydric alcohol. Examples of sugar alcohols include, but are not limited to, sorbitol, mannitol, maltitol, lactitol, erythritol, glycerin, xylitol, or inositol. [0938] According to the present disclosure, pharmaceutical compositions that include sucrose as a stabilizer are provided. Without wishing to be bound by theory, sucrose functions to promote cryoprotection of the composition, thereby preventing RNA lipoplex particle aggregation and maintaining chemical and physical stability of the composition. Certain embodiments contemplate alternative stabilizers to sucrose in the present disclosure. Alternative stabilizers include, without limitation, trehalose, glucose, fructose, arginin, glycerin, mannitol, prolin, sorbitol, glycine betaine and dextran. In some embodiments, an alternative stabilizer to sucrose is trehalose. [0939] In some embodiments, the stabilizer is at a concentration from about 5% (w/v) to about 35% (w/v), or from about 10% (w/v) to about 25% (w/v). In specific embodiments, the stabilizer is at a concentration of about 10% (w/v), about 11% (w/v), about 12% (w/v), about 13% (w/v), about 14% (w/v), about 15% (w/v), about 16% (w/v), about 17% (w/v), about 18% (w/v), about 19% (w/v), about 20% (w/v), about 21% (w/v), about 22% (w/v), about 23% (w/v), about 24% (w/v), or about 25% (w/v). In some embodiments, the stabilizer is at a concentration from about 15% (w/v) to about 25% (w/v). In some embodiments, the stabilizer is at a concentration from about 20% (w/v) to about 25% (w/v). In some embodiments, the stabilizer is at a concentration of about 25% (w/v). In some embodiments, the stabilizer is at a concentration of about 22% (w/v). In embodiments of the disclosure, the stabilizer is sucrose or trehalose. In an embodiment of the disclosure, the stabilizer is sucrose. In an embodiment of the disclosure, the stabilizer is trehalose. [0940] According to the present disclosure, the RNA lipoplex particle compositions described herein have a stabilizer concentration suitable for the stability of the composition, in particular for the stability of the RNA lipoplex particles and for the stability of the RNA. [0941] According to the present disclosure, the RNA lipoplex particle compositions described herein have a pH suitable for the stability of the RNA lipoplex particles and, in particular, for the stability of the RNA. In some embodiments, the RNA lipoplex particle compositions described herein have a pH from about 5.7 to about 6.7. In specific embodiments, the compositions have a pH of about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, or about 6.7. [0942] According to the present disclosure, compositions that include buffer are provided. Without wishing to be bound by theory, the use of buffer maintains the pH of the composition during manufacturing, storage and use of the composition. In certain embodiments of the present disclosure, WSGR Docket No.50401-795.601 the buffer may be sodium bicarbonate, monosodium phosphate, disodium phosphate, monopotassium phosphate, dipotassium phosphate, [tris(hydroxymethyl)methylamino]propanesulfonic acid (TAPS), 2-(Bis(2- hydroxyethyl)amino)acetic acid (Bicine), 2-Amino-2-(hydroxymethyl)propane-l,3-diol (Tris), N-(2-Hydroxy-l,l-bis(hydroxymethyl)ethyl)glycine (Tricine), 3-[[l ,3-dihydroxy-2- (hydroxymethyl)propan-2-yl]amino]-2-hydroxypropane-l -sulfonic acid (TAPSO), 2-[4-(2- hydroxyethyl)piperazin-l-yl]ethanesulfonic acid (HEPES), 2-[[l,3-dihydroxy-2- (hydroxymethyl)propan-2-yl]amino]ethanesulfonic acid (TES), 1,4- piperazinediethanesulfonic acid (PIPES), dimethylarsinic acid, 2-morpholin-4- ylethanesulfonic acid (MES), 3-morpholino-2- hydroxypropanesulfonic acid (MOPSO), or phosphate buffered saline (PBS). Other suitable buffers may be acetic acid in a salt, citric acid in a salt, boric acid in a salt and phosphoric acid in a salt. [0943] In some embodiments, the buffer has a pH from about 5.7 to about 6.7. In specific embodiments, the buffer has a pH of about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, or about 6.7. In some embodiments, the buffer is HEPES. In some embodiments, the HEPES has a pH from about 5.7 to about 6.7. In specific embodiments, the HEPES has a pH of about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, or about 6.7. In some embodiments, the HEPES has a pH of about 6.2. [0944] In some embodiments, the buffer has a concentration from about 2.5 mM to about 10 mM. In specific embodiments where HEPES is the buffer, the concentration of HEPES is about 2.5 mM, about 2.75 mM, 3.0 mM, about 3.25 mM, about 3.5 mM, about 3.75 mM, about 4.0 mM, about 4.25 mM, about 4.5 mM, about 4.75 mM, about 5.0 mM, about 5.25 mM, about 5.5 mM, about 5.75 mM, about 6.0 mM, about 6.25 mM, about 6.5 mM, about 6.75 mM, about 7.0 mM, about 7.25 mM, about 7.5 mM, about 7.75 mM, about 8.0 mM, about 8.25 mM, about 8.5 mM, about 8.75 mM, about 9.0 mM, about 9.25 mM, about 9.5 mM, about 9.75 mM, or about 10.0 mM. In some embodiments, the HEPES is at a concentration of about 7.5 mM. [0945] Certain embodiments of the present disclosure contemplate the use of a chelating agent. Chelating agents refer to chemical compounds that are capable of forming at least two coordinate covalent bonds with a metal ion, thereby generating a stable, water-soluble complex. Without wishing to be bound by theory, chelating agents reduce the concentration of free divalent ions, which may otherwise induce accelerated RNA degradation in the present disclosure. Examples of suitable chelating agents include, without limitation, ethylenediaminetetraacetic acid (EDTA), a salt of EDTA, desferrioxamine B, deferoxamine, dithiocarb sodium, penicillamine, pentetate calcium, a sodium salt of pentetic acid, succimer, trientine, nitrilotriacetic acid, trans-diaminocyclohexanetetraacetic acid (DCTA), diethylenetriaminepentaacetic acid (DTP A), bis(aminoethyl)glycolether-N,N,N',N'- tetraacetic acid, iminodiacetic acid, citric acid, tartaric acid, fumaric acid, or a salt thereof. In certain WSGR Docket No.50401-795.601 embodiments, the chelating agent is EDTA or a salt of EDTA. In some embodiments, the chelating agent is EDTA disodium dihydrate. [0946] In some embodiments, the EDTA is at a concentration from about 0.25 mM to about 5 mM. In specific embodiments, the EDTA is at a concentration of about 0.25 mM, about 0.3 mM, about 0.4 mM, about 0.5 mM, about 0.6 mM, about 0.7 mM, about 0.8 mM, about 0.9 mM, about 1.0 mM, about 1.1 mM, about 1.2 mM, about 1.3 mM, about 1.4 mM, about 1.5 mM, about 1.6 mM, about 1.7 mM, about 1.8 mM, about 1.9 mM, about 2.0 mM, about 2.1 mM, about 2.2 mM, about 2.3 mM. about 2.4 mM, about 2.5 mM, about 2.6 mM, about 2.7 mM, about 2.8 mM, about 2.9 mM, about 3.0 mM, about 3.1 mM, about 3.2 mM, about 3.3 mM, about 3.4 mM, about 3.5 mM, about 3.6 mM, about 3.7 mM, about 3.8 mM, about 3.9 mM, about 4.0 mM, about 4.1 mM, about 4.2 mM, about 4.3 mM, about 4.4 mM, about 4.5 mM, about 4.6 mM, about 4.7 mM, about 4.8 mM, about 4.9 mM, or about 5.0 mM. In some embodiments, the EDTA is at a concentration of about 2.5 mM. [0947] The vaccine formation described herein can be applicable to cell-based therapies. In some embodiments, the vaccine formulation comprises a TCR embedded in a liposome. In some embodiments, the vaccine formulation comprises a recombinant nucleic acid encoding a TCR embedded in a liposome. In some embodiments, the vaccine formulation comprises a cell comprising a TCR embedded in a liposome. In some embodiments, the vaccine formulation comprises a cell comprising a recombinant acid encoding a TCR embedded in a liposome. [0948] In some embodiments, the vaccine formulation comprises a TCR embedded in a lipid nanoparticle. In some embodiments, the vaccine formulation comprises a recombinant nucleic acid encoding a TCR embedded in a lipid nanoparticle. In some embodiments, the vaccine formulation comprises a cell comprising a TCR embedded in a lipid nanoparticle. In some embodiments, the vaccine formulation comprises a cell comprising a recombinant acid encoding a TCR embedded in a lipid nanoparticle. [0949] In some embodiments, the vaccine formulation comprises a TCR embedded in a lipoplex. In some embodiments, the vaccine formulation comprises a recombinant nucleic acid encoding a TCR embedded in a lipoplex. In some embodiments, the vaccine formulation comprises a cell comprising a TCR embedded in a lipoplex. In some embodiments, the vaccine formulation comprises a cell comprising a recombinant acid encoding a TCR embedded in a lipoplex. EXAMPLES [0950] The present disclosure will be more specifically illustrated by the following Examples. However, it should be understood that the present disclosure is not limited by these examples in any manner. Example 1: KRAS Constructs Elicit T cell Responses WSGR Docket No.50401-795.601 [0951] A T cell activation assay was performed to test the efficacy of KRAS vaccine constructs in eliciting T cell responses. First, monocyte derived dendritic cells (moDCs) were transfected using MessengerMAX with an equimolar amount of either (1) the construct depicted in FIG.1, comprising one repeat each of three different KRAS mutants (KRAS 1x), (2) a construct comprising three repeats each of the KRAS mutants (KRAS 3x), or (3) an irrelevant mRNA construct as a negative control. Construct sequences are summarized in Table 1 and Table 2. Table 5 shows possible epitopes processed from the constructs. [0952] After 24 hours, transfected moDCs were cocultured with engineered T cells bearing TCRs recognizing either (1) the G12V KRAS mutant presented by MHCII encoded by allele HLA- DRB1:07:01, (2) the G12V KRAS mutant presented by MHCI encoded by allele HLA-A11:01, (3) the G12D KRAS mutant presented by MHCI encoded by allele HLA-A11:01, or (4) the G12D KRAS mutant presented by MHCI encoded by allele HLA-C08:02. TCR sequences are summarized in Table 3 and Table 4. After 24 hours of coculture, supernatant was collected and IFN-γ levels were quantified via a MesoScale Discovery kit according to manufacturer’s instructions. This was performed using cells from two donors. As shown in FIGs.3A-3D, both KRAS mRNA constructs tested elicited T cell activation as indicated by IFN-γ production. This demonstrated that both the KRAS 1x and KRAS 3x constructs were capable of inducing T cell responses when expressed in antigen presenting cells (APCs). [0953] Table 1. KRAS Construct Nucleotide Sequences WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 [0954] Table 2. KRAS construct Amino Acid Sequences WSGR Docket No.50401-795.601 [0955] Table 3. KRAS-specific TCR Nucleotide Sequences WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 [0957] Table 5. Processed Mutant KRAS Epitopes WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 Example 2. Codon Optimized KRAS Constructs Codon optimized constructs were designed as described in Table 6. The amino acid sequences encoded by the constructs are summarized in Table 7. [0958] Table 6. Codon Optimized KRAS Construct Nucleotide Sequences WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 WSGR Docket No.50401-795.601 [0959] Table 7. Amino Acid Sequences Encoded by Codon Optimized KRAS Constructs in Table 6 WSGR Docket No.50401-795.601 [0960] In order to test the efficacy of the codon optimized constructs, a T cell activation assay was performed to test the ability of the constructs to elicit T cell responses. First, monocyte derived dendritic cells (moDCs) were transfected using MessengerMAX with an equimolar amount of the constructs shown in Table 6. [0961] After 24 hours, transfected moDCs were cocultured with engineered T cells bearing TCRs recognizing the KRAS G12V mutant and HLA allele HLA-A*11:01. After 24 hours of coculture, supernatant was collected and IFN-γ levels were quantified via a MesoScale Discovery kit according to manufacturer’s instructions. This was performed using cells from two donors. As shown in FIG.4, the tested constructs elicited T cell activation as indicated by IFN-γ production. This demonstrated that these codon optimized constructs are capable of inducing T cell responses when expressed in antigen presenting cells (APCs). [0962] While preferred embodiments of the present disclosure have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

WSGR Docket No.50401-795.601 CLAIMS WHAT IS CLAIMED IS: 1. A method of treating a subject with a disease or condition comprising administering to the subject a therapy comprising (i) a multiepitopic polypeptide, (ii) a recombinant nucleic acid encoding the multiepitopic polypeptide, or (iii) a cell comprising the multiepitopic polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length RAS polypeptide and comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, wherein the first RAS epitope sequence and the second RAS epitope sequence are different, and wherein presentation of the first and/or second RAS epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the therapy is higher than the presentation of the first and/or second RAS epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. 2. A method of treating a subject with a disease or condition comprising administering to the subject a therapy comprising (i) a multiepitopic polypeptide, (ii) a recombinant nucleic acid encoding the multiepitopic polypeptide, or (iii) a cell comprising the multiepitopic polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length RAS polypeptide and comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, wherein the first RAS epitope sequence and the second RAS epitope sequence are different, and wherein the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker. 3. The method of claim 1 or 2, wherein the full-length RAS polypeptide is a full-length KRAS, NRAS or HRAS polypeptide, wherein the first RAS amino acid sequence is a first KRAS, NRAS or HRAS amino acid sequence, and wherein the second RAS amino acid sequence is a second KRAS, NRAS or HRAS amino acid sequence. 4. The method of any one of claims 1-3, further comprising administering the subject a T-cell receptor (TCR), a recombinant nucleic acid encoding the TCR or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR. 5. The method of any one of claims 1-4, wherein the first RAS epitope sequence and the second RAS epitope sequence is separated by a linker. WSGR Docket No.50401-795.601 6. The method of any one of claims 1-5, wherein the first RAS amino acid sequence is the first epitope sequence and/or the second RAS amino acid sequence is the second epitope sequence. 7. The method of any one of claims 1-4, wherein the first RAS amino acid sequence comprises a first RAS mutation, and/or the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation. 8. The method of claim 7, wherein the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C. 9. The method of claim 7 or 8, wherein the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C. 10. The method of any one of claims 7-9, wherein the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell. 11. The method of any one of claims 7-9, wherein the first RAS mutation is G12V, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72. 12. The method of any one of claims 7-9, wherein the first RAS mutation is G12D, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79. 13. The method of any one of claims 7-9, wherein the first RAS mutation is G12C, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096. 14. The method of any one of claims 1-13, wherein the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length RAS polypeptide. 15. The method of any one of claims 1-13, wherein the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length RAS polypeptide. 16. The method of any one of claims 1 and 3-15, wherein the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker. 17. The method of any one of claims 1-16, wherein the first RAS amino acid sequence comprises the first RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first RAS epitope sequence from the full-length RAS polypeptide. 18. The method of any one of claims 1-17, wherein the second RAS amino acid sequence comprises the second RAS epitope sequence and one or more residues flanking the N- terminus or the C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide. WSGR Docket No.50401-795.601 19. The method of any one of claims 1-18, wherein the multiepitopic polypeptide does not comprise more than 12 or more consecutive amino acids from the full-length RAS polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length RAS polypeptide. 20. The method of any one of claims 4-19, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the first or the second RAS epitope sequence, and (ii) a human MHC encoded by an HLA allele. 21. The method of any one of claims 1-20, wherein the multiepitopic polypeptide is a RAS polypeptide comprising the first RAS epitope sequence and the second RAS epitope sequence. 22. The method of any one of claims 2-21, wherein the linker is a cleavable linker. 23. A method of treating a subject with a disease or condition comprising administering to the subject (a) a RAS polypeptide, (b) a recombinant nucleic acid encoding the RAS polypeptide, or (c) a cell comprising the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide, wherein the RAS polypeptide comprises a RAS epitope sequence, wherein the subject has been previously administered a T-cell receptor (TCR), a recombinant nucleic acid encoding the TCR, or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS epitope sequence, and (ii) a human MHC encoded by an HLA allele. 24. A method of treating a subject with a disease or condition comprising administering to the subject a T-cell receptor (TCR), a recombinant nucleic acid encoding the TCR or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) a RAS epitope sequence, and (ii) a human MHC encoded by an HLA allele, wherein the subject has been previously administered (a) a RAS polypeptide, (b) a recombinant nucleic acid encoding the RAS polypeptide, or (c) a cell comprising the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide, wherein the RAS polypeptide comprises the RAS epitope sequence. 25. A method of treating a subject with a disease or condition comprising, (a) administering to the subject (i) a RAS polypeptide, (ii) a recombinant nucleic acid encoding the RAS polypeptide, or (iii) a cell comprising the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide, wherein the RAS polypeptide comprises a RAS epitope sequence; and WSGR Docket No.50401-795.601 (b) administering to the subject a TCR, a recombinant nucleic acid encoding the TCR or a cell comprising the TCR or the recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide:MHC complex, the peptide:MHC complex comprising (i) the RAS peptide sequence, and (ii) a human MHC encoded by an HLA allele. 26. The method of claim 25, wherein administering in (a) is performed concurrently with administering in (b). 27. The method of claim 25, wherein administering in (a) is prior to administering in (b). 28. The method of claim 25, wherein administering in (a) is subsequent to administering in (b). 29. The method of any one of claims 23, 25 and 28, wherein the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide is administered at least 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years or more after the subject has been administered the TCR or the recombinant nucleic acid encoding the TCR. 30. The method of any one of claims 24, 25 and 27, wherein the TCR or the recombinant nucleic acid encoding the TCR is administered at least 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years or more after the subject has been administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide. 31. The method of any one of claims 4-30, wherein the cell is an immune cell. 32. The method of any one of claims 4-31, wherein the T-cell receptor (TCR) or the recombinant nucleic acid encoding the TCR is expressed by an immune cell. 33. The method of any one of claims 4-30, wherein the TCR is a soluble TCR. 34. The method of any one of claims 4-33, further comprising administering two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs, or cells comprising the two or more different TCRs or the recombinant nucleic acids encoding the two or more different TCRs and wherein the two or more different TCRs comprise a first TCR and a second TCR. 35. The method of claim 34, wherein the two or more different TCRs are expressed on surface of two different immune cells. 36. The method of claim 34 or 35, wherein the first TCR and the second TCR bind to different peptide:MHC complexes, each peptide:MHC complex comprising (i) an epitope sequence and (ii) a human MHC encoded by an HLA allele. WSGR Docket No.50401-795.601 37. The method of any one of claims 34-36, wherein the two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs are administered separately or co-administered in a same mixture. 38. The method of any one of claims 34-37, wherein the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12V mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, and the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12D mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA- A*68:01. 39. The method of any one of claims 34-37, wherein the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12V mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, and the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12C mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. 40. The method of any one of claims 34-37, wherein the first TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12D mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA- C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01, and the second TCR binds to a peptide:MHC complex comprising an epitope sequence having a G12C mutation and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. 41. The method of any one of claims 34-37, wherein the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75-79 and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA- WSGR Docket No.50401-795.601 C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01; the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72 and an MHC encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA- A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01 and, HLA-A*03 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03; or the first TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 28, 75-79 and an MHC encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, and HLA-A*68:01 and the second TCR binds to a peptide:MHC complex comprising an epitope sequence selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096 and an MHC encoded by an HLA allele selected from the group consisting HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA- A*68:01, and HLA-C*03:03. 42. The method of any one of claims 23-38, wherein the RAS polypeptide does not comprise a full-length RAS protein sequence. 43. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 59. 44. The method of claim 43, wherein the HLA allele is selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*03:02, HLA-A*03:05, HLA- B*40:01, and HLA-A*68:01. 45. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence of SEQ ID NO: 60. 46. The method of claim 40, wherein the HLA allele is HLA-C*01:02. 47. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence of SEQ ID NOs: 61 or 62. 48. The method of claim 47, wherein the HLA allele is HLA-C*03:03, or HLA-C*03:04. 49. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence of SEQ ID NOs: 58 or 59. 50. The method of claim 49, wherein the MHC allele is HLA-A*11:01. 51. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 65-71. WSGR Docket No.50401-795.601 52. The method of claim 51, wherein the MHC allele is HLA-DRB1*07:01. 53. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 58 or 72. 54. The method of claim 53, wherein the MHC allele is selected from the group consisting of HLA-A*03:01, HLA-A*03:02, and HLA-A*03:05. 55. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence of SEQ ID NO: 75. 56. The method of claim 55, wherein the MHC allele is selected from the group consisting of HLA-B*07:02, HLA-C*08:02, HLA-C*03:04, and HLA-C*05:01. 57. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence of SEQ ID NO: 76. 58. The method of claim 57, wherein the MHC allele is selected from the group consisting of HLA-A*3:01, HLA-A*11:01, and HLA-A*68:01. 59. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence of SEQ ID NO: 77. 60. The method of claim 59, wherein the MHC allele is HLA-A*11:01. 61. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence of SEQ ID NOs: 78 or 79. 62. The method of claim 61, wherein the MHC allele is HLA-C*08:02. 63. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence of SEQ ID NO: 29. 64. The method of claim 63, wherein the MHC allele is HLA-DRB1*11:01. 65. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence of SEQ ID NO: 81 or 1096. 66. The method of claim 65, wherein the MHC allele is selected from the group consisting of HLA-A*3:01, HLA-A*11:01, and HLA-A*68:01. 67. The method of any one of claims 23-42, wherein the RAS epitope sequence comprises a sequence of SEQ ID NO: 82. 68. The method of claim 67, wherein the MHC allele is HLA-C*03:03. 69. The method of any one of claims 21-68, wherein the RAS polypeptide is a multiepitopic polypeptide, and wherein the multiepitopic polypeptide does not comprise a full-length RAS polypeptide and comprises two or more different RAS epitope sequences. 70. The method of claim 69, wherein the multiepitopic polypeptide comprises at least 3, 4, 5, or more different RAS epitope sequences. WSGR Docket No.50401-795.601 71. The method of claim 69 or 70, wherein the two or more different RAS epitope sequences are separated by linker sequences. 72. The method of any one of claims 69-71, wherein antigen presenting cells (APCs) of the subject administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide comprising the multiepitopic polypeptide present more of a RAS epitope sequence as a peptide:MHC complex compared to the APCs of a subject administered a full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. 73. The method of any one of claims 69-72, wherein T cells of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide exhibit increased expansion compared to T cells of a subject administered a full-length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. 74. The method of any one of claims 69-73, wherein the multiepitopic polypeptide comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, and wherein the first RAS epitope sequence and the second RAS epitope sequence are different or wherein the first RAS amino acid sequence and the second RAS amino acid sequence comprise different RAS mutations. 75. The method of claim 74, wherein the first RAS epitope sequence and the second RAS epitope sequence is separated by a linker. 76. The method of claim 74 or 75, wherein the first amino acid sequence is the first epitope sequence and/or the second amino acid sequence is the second epitope sequence. 77. The method of any one of claims 74-76, wherein the first amino acid sequence consists of the first epitope sequence, and/or the second amino acid sequence consists of the second epitope sequence. 78. The method of any one of claims 74-77, wherein the first RAS amino acid sequence comprises a first RAS mutation, and/or the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation. 79. The method of claim 78, wherein the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C. 80. The method of claim 78 or 79, wherein the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C. 81. The method of any one of claims 78-80, wherein the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell. WSGR Docket No.50401-795.601 82. The method of any one of claims 78-80, wherein the first RAS mutation is G12V, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72. 83. The method of any one of claims 78-80, wherein the first RAS mutation is G12D, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79. 84. The method of any one of claims 78-80, wherein the first RAS mutation is G12C, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096. 85. The method of any one of claims 74-84, wherein the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length RAS polypeptide. 86. The method of any one of claims 74-84, wherein the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length RAS polypeptide. 87. The method of any one of claims 74-86, wherein the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker. 88. The method of any one of claims 74, 75 and 85-87, wherein the first amino acid sequence comprises the first RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first RAS epitope sequence from the full-length RAS polypeptide. 89. The method of any one of claims 74, 75 and 85-88, wherein the second amino acid sequence comprises the second RAS epitope sequence and one or more residues flanking the N- terminus or the C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide. 90. The method of any one of claims 69-89, wherein the multiepitopic polypeptide does not comprise more than 12 or more consecutive amino acids from the full-length RAS polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length RAS polypeptide. 91. The method of any one of claims 74-90, wherein the first RAS epitope sequence and the second RAS epitope sequence are presentable by different HLA alleles, are presented by different HLA alleles, bind to different HLA alleles, are predicted to bind to different HLA alleles, or are predicted to be presented by different HLA alleles. 92. The method of any one of claims 74-91, wherein a first RAS epitope sequence (i) binds to or is predicted to bind to a first HLA allele with a KD of less than 100 nM and (ii) to binds to or is predicted to bind to a second HLA allele with a KD of more than 500 nM. WSGR Docket No.50401-795.601 93. The method of any one of claims 74-92, wherein the first amino acid sequence is operably linked to the second amino acid sequence via a linker. 94. The method of claim 93, wherein the linker is a cleavable linker. 95. The method of claim 93 or 94, wherein the linker comprises a sequence of SEQ ID NO: 31. 96. The method of any one of claims 69-95, wherein the multiepitopic polypeptide comprises a first amino acid sequence comprising a first RAS epitope sequence, operably linked to a second amino acid sequence comprising a second RAS epitope sequence, operably linked to a third amino acid sequence comprising a third RAS epitope sequence. 97. The method of claim 96, wherein the first RAS epitope sequence, the second RAS epitope sequence, and/or the third RAS epitope sequence comprises a RAS mutation selected from the group consisting of G12V, G12D, and G12C, and wherein the first RAS epitope sequence, the second RAS epitope sequence, and the third RAS epitope sequence comprise different RAS mutations. 98. The method of claim 97, wherein the first RAS epitope sequence comprises a G12V mutation. 99. The method of claim 97 or 98,wherein the second RAS epitope sequence comprises a G12D mutation. 100. The method of any one of claims 97-99, wherein the third RAS epitope sequence comprises a G12C mutation. 101. The method of any one of claims 96-100, wherein (i) the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA- A*03:02, and HLA-A*03:05, binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA- A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA- A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, WSGR Docket No.50401-795.601 HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, (ii) the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA- C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA- A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA- C*08:02, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA- A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, and (iii) the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA- A*68:01, and HLA-C*03:03, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. 102. The method of any one of claims 69-101, wherein the subject does not express an HLA allele that recognizes each RAS epitope sequence of the multiepitopic polypeptide. 103. The method of any one of claims 69-102, wherein the subject only expresses HLA alleles that recognize a subset of RAS epitope sequences of the multiepitopic polypeptide. 104. The method of any one of claims 24-101, wherein the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. 105. The method of claim 104, wherein the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. 106. The method of claim 104, wherein the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. WSGR Docket No.50401-795.601 107. The method of claim 104, wherein the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 27-29. 108. The method of claim 104, wherein the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 27, operably linked to a sequence of SEQ ID NO: 29, and operably linked to a sequence of SEQ ID NO: 28. 109. The method of claim 108, wherein the sequence of SEQ ID NO: 27 is operably linked to the sequence of SEQ ID NOs: 29 via a linker, and the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker. 110. The method of claim 109, wherein the linker is a cleavable linker. 111. The method of claim 110, wherein the linker comprises a sequence of SEQ ID NO: 31. 112. The method of claim 104, wherein the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NOs: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. 113. The method of claim 112, wherein the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker. 114. The method of claim 113, wherein the linker is a cleavable linker. 115. The method of claim 114, wherein the linker comprises a sequence of SEQ ID NO: 31. 116. The method of claim 104, wherein the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 28, operably linked to a sequence of SEQ ID NO: 27, and operably linked to a sequence of SEQ ID NO: 29. 117. The method of claim 116, wherein the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 is operably linked to a sequence of SEQ ID NO: 29 via a linker. 118. The method of claim 117, wherein the linker is a cleavable linker. 119. The method of claim 118, wherein the linker comprises a sequence of SEQ ID NO: 31. 120. The method of claim 104, wherein the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 27, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 29. 121. The method of claim 120, wherein the sequence of SEQ ID NO: 27 is operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 is operably linked to a sequence of SEQ ID NO: 29 via a linker. 122. The method of claim 121, wherein the linker is a cleavable linker. 123. The method of claim 122, wherein the linker comprises a sequence of SEQ ID NO: 31. WSGR Docket No.50401-795.601 124. The method of claim 104, wherein the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 28, operably linked to a sequence of SEQ ID NO: 29, and operably linked to a sequence of SEQ ID NO: 27. 125. The method of claim 124, wherein the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 29 via a linker, and the sequence of SEQ ID NO: 29 is operably linked to a sequence of SEQ ID NO: 27 via a linker. 126. The method of claim 125, wherein the linker is a cleavable linker. 127. The method of claim 126, wherein the linker comprises a sequence of SEQ ID NO: 31. 128. The method of claim 104, wherein the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 27, and operably linked to a sequence of SEQ ID NO: 28. 129. The method of claim 128, wherein the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 is operably linked to a sequence of SEQ ID NO: 28 via a linker. 130. The method of claim 129, wherein the linker is a cleavable linker. 131. The method of claim 130, wherein the linker comprises a sequence of SEQ ID NO: 31. 132. The method of any one of claims 21-119, wherein the RAS polypeptide comprises at least two copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. 133. The method of claim 132, wherein the RAS polypeptide comprises three copies of the multiepitopic polypeptide. 134. The method of claim 132, wherein the RAS polypeptide comprises five copies of the multiepitopic polypeptide. 135. The method of any one of claims 23-134, wherein the RAS polypeptide further comprises a secretory domain (Sec) sequence at the N terminus of the multiepitopic polypeptide. 136. The method of claim 135, wherein the Sec sequence comprises a sequence of SEQ ID NO: 32. 137. The method of claim 135 or 136, wherein the Sec sequence is operably linked to the multiepitopic polypeptide via a linker. 138. The method of claim 137, wherein the linker comprises a sequence of SEQ ID NO: 30 or 31. 139. The method of any one of claims 23-138, wherein the RAS polypeptide further comprises an MHC class I trafficking domain (MITD) sequence at the C terminus of the multiepitopic polypeptide. WSGR Docket No.50401-795.601 140. The method of claim 139, wherein the MITD sequence comprises a sequence of SEQ ID NO: 33. 141. The method of claim 139 or 140, wherein the multiepitopic polypeptide is operably linked to the MITD sequence via a linker. 142. The method of claim 141, wherein the linker comprises a sequence of SEQ ID NO: 30 or 112. 143. The method of any one of claims 23-142, wherein the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 25. 144. The method of any one of claims 23-142, wherein the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 26. 145. The method of any one of claims 23-142, wherein the RAS polypeptide comprises a sequence having at least 80% sequence identity to a sequence of SEQ ID NO: 113. 146. The method of any one of claims 23-145, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. 147. The method of claim 146, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. 148. The method of claim 146, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104- 106, 108-110. 149. The method of claim 146, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 14- 23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. 150. The method of claim 146, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17- 19, 86, 93, 97, 101, 105, and 109. 151. The method of claim 150, wherein the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, WSGR Docket No.50401-795.601 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109via a linker sequence. 152. The method of claim 151, wherein the linker sequence encodes a cleavable linker. 153. The method of claim 152, wherein the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13, 85, 87, and 89. 154. The method of claim 146, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14- 16, 84, 92, 96, 100, 104, and 108. 155. The method of claim 154, wherein the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 via a linker sequence. 156. The method of claim 155, wherein the linker sequence encodes a cleavable linker. 157. The method of claim 156, wherein the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13, 85, 87, and 89. 158. The method of claim 146, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20- 23, 88, 94, 98, 102, 106, and 110. 159. The method of claim 158, wherein the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 is operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 via a linker sequence. 160. The method of claim 159, wherein the linker sequence is a cleavable linker. 161. The method of claim 160, wherein the linker sequence comprises a sequence of selected from the group consisting of SEQ ID NOs: 5, 6, 8-13, 85, 87, and 89. WSGR Docket No.50401-795.601 162. The method of claim 146, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises at least two copies of a string of sequences, and wherein each string of sequences comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. 163. The method of claim 162, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of the string of sequences. 164. The method of claim 162, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of the string of sequences. 165. The method of any one of claims 146-164, wherein the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a secretory (Sec) sequence at the 5’end of the string of sequences. 166. The method of claim 165, wherein the sequence encoding the Sec sequence comprises a sequence of SEQ ID NO: 3. 167. The method of claim 165 or 166, wherein the sequence encoding the Sec sequence is operably linked to the string of sequences via a linker sequence. 168. The method of any one of claims 165-167, wherein the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. 169. The method of any one of claims 146-168, wherein the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MITD sequence at the 3’ end of the string of sequences. 170. The method of claim 169, wherein the sequence encoding the MITD domain comprises a sequence of SEQ ID NO: 24 or 90. 171. The method of claim 169 or 170, wherein the string of sequences is operably linked to the sequence encoding the MITD sequence via a linker sequence. 172. The method of any one of claims 169-171, wherein the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, and 89. 173. The method of any one of claims 146-172, wherein the recombinant nucleic acid is codon- optimized. 174. The method of any one of claims 146-173, wherein the recombinant nucleic acid is an RNA. 175. The method of any one of claims 146-174, wherein the recombinant nucleic acid comprises a sequence having at least 60% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 91, 95, 99, 103, 107, 111. WSGR Docket No.50401-795.601 176. The method of any one of claims 173-175, wherein the subject expresses more of the RAS epitope when administered with the codon-optimized recombinant nucleic acid than administered with wild-type recombinant nucleic acid. 177. The method of any one of claims 20-176, wherein the TCR comprises a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR beta chain construct comprises a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO: 57. 178. The method of claim 177, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence with at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 52 or SEQ ID NO: 53. 179. The method of claim 177 or 178, wherein the TCR beta chain construct comprises a complementarity determining region 1 (CDR1) having an amino acid sequence set forth in SEQ ID NO: 55 and a complementarity determining region 2 (CDR2) having an amino acid sequence set forth in SEQ ID NO: 56. 180. The method of any one of claims 177-179, wherein the TCR alpha chain construct comprises a CDR1, a CDR2, and a CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 46, the CDR2 has an amino acid sequence set forth in SEQ ID NO: 47, and the CDR3 has an amino acid sequence set forth in SEQ ID NO: 48. 181. The method of any one of claims 177-180, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 43 or SEQ ID NO: 44. 182. The method of any one of claims 177-181, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NO: 49 or SEQ ID NO: 51, or an amino acid sequence that is at least 80% identical to SEQ ID NO: 49 or SEQ ID NO: 51, and (b) an alpha chain having an amino acid sequence set forth in SEQ ID NO: 40 or SEQ ID NO: 42, or an amino acid sequence that is at least 80% identical to SEQ ID NO: 40 or SEQ ID NO: 42. 183. The method of any one of claims 20-176, wherein the TCR is selected from the TCRs presented in Tables 8A-8D. 184. The method of any one of claims 32-183, wherein binding of the TCR to the peptide:MHC complex results in production of a cytokine by the immune cell. 185. The method of claim 184, wherein the cytokine is IFN-γ, TNF-α, IL-2, IL-18, or any combination thereof. 186. A recombinant nucleic acid encoding a RAS polypeptide comprising a multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length RAS WSGR Docket No.50401-795.601 polypeptide and comprises a first RAS amino acid sequence comprising a first RAS epitope sequence and a second RAS amino acid sequence comprising a second RAS epitope sequence, wherein the first RAS epitope sequence and the second RAS epitope sequence are different, and wherein the first RAS amino acid sequence and the second RAS amino acid sequence are linked via a linker. 187. The recombinant nucleic acid of claim 186, wherein presentation of the first and/or second RAS epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the RAS polypeptide or the recombinant nucleic acid encoding the RAS polypeptide is higher than the presentation of the first and/or second RAS epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full- length RAS polypeptide or a recombinant nucleic acid encoding the full-length RAS polypeptide. 188. The recombinant nucleic acid of claim 186 or 187, wherein the first RAS amino acid sequence is the first epitope sequence and/or the second RAS amino acid sequence is the second epitope sequence. 189. The recombinant nucleic acid of any one of claims 186-188, wherein the first RAS amino acid sequence consists of the first epitope sequence, and/or the second RAS amino acid sequence consists of the second epitope sequence. 190. The recombinant nucleic acid of any one of claims 186-189, wherein the first RAS amino acid sequence comprises a first RAS mutation, and/or the second RAS amino acid sequence comprises a second RAS mutation different from the first RAS mutation. 191. The recombinant nucleic acid of claim 190, wherein the first RAS mutation is selected from the group consisting of G12V, G12D, and G12C. 192. The recombinant nucleic acid of claim 190 or 191, wherein the second RAS mutation is selected from the group consisting of G12V, G12D, and G12C. 193. The recombinant nucleic acid of any one of claims 190-192, wherein the first RAS amino acid sequence is processed into one or more epitopes comprising the first RAS mutation within a cell. 194. The recombinant nucleic acid of any one of claims 190-193, wherein the first RAS mutation is G12V, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 27, 58-62 and 65-72. 195. The recombinant nucleic acid of any one of claims 190-193, wherein the first RAS mutation is G12D, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 28, 75-79. WSGR Docket No.50401-795.601 196. The recombinant nucleic acid of any one of claims 190-193, wherein the first RAS mutation is G12C, and wherein the one or more epitopes are selected from the group consisting of SEQ ID NOs: 29, 81, 82, and 1096. 197. The recombinant nucleic acid of any one of claims 186-196, wherein the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length RAS polypeptide. 198. The recombinant nucleic acid of any one of claims 186-189, wherein the first RAS epitope sequence and/or the second RAS epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length RAS polypeptide. 199. The recombinant nucleic acid of any one of claims 186-198, wherein the first RAS amino acid sequence and the second RAS amino acid sequence is separated by a linker. 200. The recombinant nucleic acid of any one of claims 186, 187 and 197-199, wherein the first RAS amino acid sequence comprises the first RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first RAS epitope sequence from the full-length RAS polypeptide. 201. The recombinant nucleic acid of any one of claims 186, 187 and 197-200, wherein the second RAS amino acid sequence comprises the second RAS epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second RAS epitope sequence from the full-length RAS polypeptide. 202. The recombinant nucleic acid of any one of claims 186-201, wherein the multiepitopic polypeptide does not comprise more than 12 or more consecutive amino acids from the full- length RAS polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length RAS polypeptide. 203. The recombinant nucleic acid of any one of claims 186-202, wherein the RAS polypeptide further comprises a Secretory (Sec) sequence at the N terminus of the multiepitopic polypeptide. 204. The recombinant nucleic acid of claim 203, wherein the Sec sequence comprises a sequence of SEQ ID NO: 32. 205. The recombinant nucleic acid of any one of claims 186-204, wherein the Sec sequence is operably linked to the multiepitopic polypeptide via a linker. 206. The recombinant nucleic acid of claim 205, wherein the linker comprises a sequence of SEQ ID NO: 30 or 31. 207. The recombinant nucleic acid of any one of claims 186-206, wherein the RAS polypeptide further comprises an MHC class I trafficking signal (MITD) sequence at the C terminus of the multiepitopic polypeptide. WSGR Docket No.50401-795.601 208. The recombinant nucleic acid of claim 207, wherein the MITD sequence comprises a sequence of SEQ ID NO: 33. 209. The recombinant nucleic acid of claim 207, wherein the multiepitopic polypeptide is operably linked to the MITD sequence via a linker. 210. The recombinant nucleic acid of claim 209, wherein the linker comprises a sequence of SEQ ID NO: 30 or 112. 211. The recombinant nucleic acid of any one of claims 186-210, wherein the multiepitopic polypeptide comprises at least 3, 4, 5, or more different RAS epitope sequences. 212. The recombinant nucleic acid of any one of claims 186-211, wherein the first RAS epitope sequence and the second RAS epitope sequence are presentable by different HLA alleles, are presented by different HLA alleles, bind to different HLA alleles, are predicted to bind to different HLA alleles, or are predicted to be presented by different HLA alleles. 213. The recombinant nucleic acid of any one of claims 186-212, wherein a first RAS epitope sequence (i) binds to or is predicted to bind to a first HLA allele with a KD of less than 100 nM and (ii) to binds to or is predicted to bind to a second HLA allele with a KD of more than 500 nM. 214. The recombinant nucleic acid of any one of claims 186-213, wherein the linker comprises a sequence of SEQ ID NO: 31 or 112. 215. The recombinant nucleic acid of claim 211, wherein the multiepitopic polypeptide comprises a first amino acid sequence comprising a first RAS epitope sequence, operably linked to a second amino acid sequence comprising a second RAS epitope sequence, operably linked to a third amino acid sequence comprising a third RAS epitope sequence. 216. The recombinant nucleic acid of claim 215, wherein (i) the first RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA- A*03:02, and HLA-A*03:05, binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA- A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA- DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA- A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, WSGR Docket No.50401-795.601 HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-A*11:01, HLA-A*03:01, HLA-A*30:01, HLA-A*68:01, HLA-B*40:01, HLA-C*01:02, HLA-C*03:03, HLA-C*03:04, HLA-DRB1*07:01, HLA-A*03:02, and HLA-A*03:05, (ii) the second RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA- C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02,binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA- A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA-A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA- C*08:02, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-B*07:02, HLA-C*03:04, HLA-C*05:01, HLA- A*-3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*08:02, and (iii) the third RAS epitope sequence is presentable by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, is presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, binds to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03, is predicted to bind to an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA- A*68:01, and HLA-C*03:03, or is predicted to be presented by an MHC molecule encoded by an HLA allele selected from the group consisting of HLA-DRB1*11:01, HLA-A*3:01, HLA-A*11:01, HLA-A*68:01, and HLA-C*03:03. 217. The recombinant nucleic acid of any one of claims 186-215, wherein the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2])x- CT seq, where x is an integer from 1 to 10. 218. The recombinant nucleic acid of any one of claims 186-215, wherein the multiepitopic polypeptide comprises the formula NT seq – ([Antigen1]-cleavable linker1-[Antigen2]- cleavable linker2-[Antigen3])x-CT seq, where x is an integer from 1 to 10. WSGR Docket No.50401-795.601 219. The recombinant nucleic acid of claim 217 or 218, wherein the NT seq comprises a Secretory (Sec) sequence and a N-terminal linker sequence. 220. The recombinant nucleic acid of any one of claims 217-219, wherein the CT seq comprises a C-terminal linker and a MITD sequence. 221. The recombinant nucleic acid of any one of claims 217-220, wherein the Antigen1, Antigen2, or Antigen3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 27-29. 222. The recombinant nucleic acid of any one of claims 217-221, wherein the cleavable linker1 or cleavable linker2 is selected from the group consisting of SEQ ID NOs: 30, 31, and 112. 223. The recombinant nucleic acid of any one of claims 219-222, wherein the N-terminal linker sequence or the C-terminal linker sequence is selected from the group consisting of SEQ ID NOs: 30, 31, and 112. 224. The recombinant nucleic acid of any one of claims 186-214, wherein the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 27- 29. 225. The recombinant nucleic acid of claim 224, wherein the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. 226. The recombinant nucleic acid of claim 224, wherein the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 27-29. 227. The recombinant nucleic acid of claim 224, wherein the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 27-29. 228. The recombinant nucleic acid of claim 224, wherein the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 27, operably linked to a sequence of SEQ ID NO: 29, and operably linked to a sequence of SEQ ID NO: 28. 229. The recombinant nucleic acid of claim 228, wherein the sequence of SEQ ID NO: 27 is operably linked to the sequence of SEQ ID NO: 29 via a linker, and the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker. 230. The recombinant nucleic acid of claim 229, wherein the linker is a cleavable linker. 231. The recombinant nucleic acid of claim 230, wherein the linker comprises a sequence of SEQ ID NO: 31. 232. The recombinant nucleic acid of claim 224, wherein the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. WSGR Docket No.50401-795.601 233. The recombinant nucleic acid of claim 232, wherein the sequence of SEQ ID NO: 29 is operably linked to the sequence of SEQ ID NO: 28 via a linker, and the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker. 234. The recombinant nucleic acid of claim 233, wherein the linker is a cleavable linker. 235. The recombinant nucleic acid of claim 234, wherein the linker comprises a sequence of SEQ ID NO: 31. 236. The recombinant nucleic acid of claim 224, wherein the RAS polypeptide comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 28, operably linked to a sequence of SEQ ID NO: 27, and operably linked to a sequence of SEQ ID NO: 29. 237. The recombinant nucleic acid of claim 236, wherein the sequence of SEQ ID NO: 28 is operably linked to the sequence of SEQ ID NO: 27 via a linker, and the sequence of SEQ ID NO: 27 is operably linked to a sequence of SEQ ID NO: 29 via a linker. 238. The recombinant nucleic acid of claim 237, wherein the linker is a cleavable linker. 239. The recombinant nucleic acid of claim 238, wherein the linker comprises a sequence of SEQ ID NO: 31. 240. The recombinant nucleic acid of claim 224, wherein the RAS polypeptide comprises at least two copies of a multiepitopic polypeptide, and wherein each copy comprises, from N terminus to C terminus, a sequence of SEQ ID NO: 29, operably linked to a sequence of SEQ ID NO: 28, and operably linked to a sequence of SEQ ID NO: 27. 241. The recombinant nucleic acid of claim 240, wherein the RAS polypeptide comprises three copies of the multiepitopic polypeptide. 242. The recombinant nucleic acid of claim 240, wherein the RAS polypeptide comprises five copies of the multiepitopic polypeptide. 243. The recombinant nucleic acid of any one of claims 186-214, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. 244. The recombinant nucleic acid of any one of claims 186-214, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96- 98, 100-102, 104-106, 108-110. 245. The recombinant nucleic acid of any one of claims 186-214, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108-110. WSGR Docket No.50401-795.601 246. The recombinant nucleic acid of any one of claims 186-214, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 14-23, 84, 86, 88, 92-94, 96-98, 100-102, 104-106, 108- 110. 247. The recombinant nucleic acid of any one of claims 186-214, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109. 248. The recombinant nucleic acid of claim 247, wherein the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence. 249. The recombinant nucleic acid of claim 248, wherein the linker sequence encodes a cleavable linker. 250. The recombinant nucleic acid of claim 249, wherein the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13, 85, 87, and 89. 251. The recombinant nucleic acid of any one of claims 186-214, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. 252. The recombinant nucleic acid of claim 251, wherein the sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108 via a linker sequence. WSGR Docket No.50401-795.601 253. The recombinant nucleic acid of claim 252, wherein the linker sequence encodes a cleavable linker. 254. The recombinant nucleic acid of claim 253, wherein the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13, 85, 87, and 89. 255. The recombinant nucleic acid of any one of claims 186-214 wherein the recombinant nucleic acid encoding the RAS polypeptide comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110. 256. The recombinant nucleic acid of claim 255, wherein the sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109 is operably linked to the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108via a linker sequence, and the sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108is operably linked to a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110 via a linker sequence. 257. The recombinant nucleic acid of claim 256, wherein the linker sequence is a cleavable linker. 258. The recombinant nucleic acid of claim 257, wherein the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 8-13, 85, 87, and 89. 259. The recombinant nucleic acid of any one of claims 186-214, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises at least two copies of a string of sequences, and wherein each string of sequences comprises, from 5’ end to 3’ end, a sequence selected from the group consisting of SEQ ID NOs: 20-23, 88, 94, 98, 102, 106, and 110, operably linked to a sequence selected from the group consisting of SEQ ID NOs: 17-19, 86, 93, 97, 101, 105, and 109, and operably linked to a sequence selected from the group consisting of SEQ ID NOs: 14-16, 84, 92, 96, 100, 104, and 108. 260. The recombinant nucleic acid of claim 259, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises three copies of the string of sequences. 261. The recombinant nucleic acid of claim 259, wherein the recombinant nucleic acid encoding the RAS polypeptide comprises five copies of the string of sequences. 262. The recombinant nucleic acid of any one of claims 186-261, wherein the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding a Sec sequence at the 5’ end of the string of sequences. WSGR Docket No.50401-795.601 263. The recombinant nucleic acid of claim 262, wherein the sequence encoding the Sec sequence comprises a sequence of SEQ ID NO: 3. 264. The recombinant nucleic acid of claim 263, wherein the sequence encoding the Sec sequence is operably linked to the string of sequences via a linker sequence. 265. The recombinant nucleic acid of claim 264, wherein the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. 266. The recombinant nucleic acid of any one of claims 186-265, wherein the recombinant nucleic acid encoding the RAS polypeptide further comprises a sequence encoding an MITD sequence at the 3’ end of the string of sequences. 267. The recombinant nucleic acid of claim 266, wherein the sequence encoding the MITD sequence comprises a sequence of SEQ ID NO: 24 or 90. 268. The recombinant nucleic acid of claim 266, wherein the string of sequences is operably linked to the sequence encoding the MITD sequence via a linker sequence. 269. The recombinant nucleic acid of claim 268, wherein the linker sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 7, 83, and 89. 270. A recombinant nucleic acid having at least 60% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 91, 95, 99, 103, 107, 111. 271. A recombinant nucleic acid having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 91, 95, 99, 103, 107, 111. 272. A polypeptide encoded by the recombinant nucleic acid of any one of claims 186-271. 273. A pharmaceutical composition comprising the recombinant nucleic acid of any one of claims 186-271 or the polypeptide of claim 272, and a pharmaceutically acceptable carrier. 274. The recombinant nucleic acid of any one of claims 186-271, the polypeptide of claim 272, or the pharmaceutical composition of claim 273 for use in therapy. 275. Use of the recombinant nucleic acid of any one of claims 186-271, the polypeptide of claim 272, or the pharmaceutical composition of claim 273, in the manufacture of a medicament for the treatment of cancer in a subject in need thereof.
PCT/US2025/026433 2024-04-25 2025-04-25 Ras vaccine compositions and methods of use Pending WO2025227066A2 (en)

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