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EP3684424A4 - CHIMERA ANTIGEN RECEPTORS WITH IMPROVED NFKB SIGNALING - Google Patents

CHIMERA ANTIGEN RECEPTORS WITH IMPROVED NFKB SIGNALING Download PDF

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Publication number
EP3684424A4
EP3684424A4 EP18859613.4A EP18859613A EP3684424A4 EP 3684424 A4 EP3684424 A4 EP 3684424A4 EP 18859613 A EP18859613 A EP 18859613A EP 3684424 A4 EP3684424 A4 EP 3684424A4
Authority
EP
European Patent Office
Prior art keywords
improved
antigen receptors
nfkb signaling
chimera antigen
chimera
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
EP18859613.4A
Other languages
German (de)
French (fr)
Other versions
EP3684424A1 (en
Inventor
Marco L. DAVILLA
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.)
H Lee Moffitt Cancer Center and Research Institute Inc
Original Assignee
H Lee Moffitt Cancer Center and Research Institute 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 H Lee Moffitt Cancer Center and Research Institute Inc filed Critical H Lee Moffitt Cancer Center and Research Institute Inc
Publication of EP3684424A1 publication Critical patent/EP3684424A1/en
Publication of EP3684424A4 publication Critical patent/EP3684424A4/en
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/31—Chimeric antigen receptors [CAR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
    • A61K40/421—Immunoglobulin superfamily
    • A61K40/4211—CD19 or B4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70521—CD28, CD152
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • C12N5/0638—Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/48—Blood cells, e.g. leukemia or lymphoma
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/50—Cell markers; Cell surface determinants
    • C12N2501/515—CD3, T-cell receptor complex
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2510/00—Genetically modified cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/13011—Gammaretrovirus, e.g. murine leukeamia virus
    • C12N2740/13041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/13043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Zoology (AREA)
  • Public Health (AREA)
  • Biochemistry (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Cell Biology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
EP18859613.4A 2017-09-22 2018-09-11 CHIMERA ANTIGEN RECEPTORS WITH IMPROVED NFKB SIGNALING Pending EP3684424A4 (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201762561815P 2017-09-22 2017-09-22
US201762597128P 2017-12-11 2017-12-11
US201862640153P 2018-03-08 2018-03-08
US201862666385P 2018-05-03 2018-05-03
US201862666381P 2018-05-03 2018-05-03
PCT/US2018/050417 WO2019060174A1 (en) 2017-09-22 2018-09-11 Chimeric antigen receptors with enhanced nfkb signaling

Publications (2)

Publication Number Publication Date
EP3684424A1 EP3684424A1 (en) 2020-07-29
EP3684424A4 true EP3684424A4 (en) 2021-09-29

Family

ID=65810869

Family Applications (1)

Application Number Title Priority Date Filing Date
EP18859613.4A Pending EP3684424A4 (en) 2017-09-22 2018-09-11 CHIMERA ANTIGEN RECEPTORS WITH IMPROVED NFKB SIGNALING

Country Status (5)

Country Link
EP (1) EP3684424A4 (en)
JP (1) JP2021500859A (en)
AU (1) AU2018335266A1 (en)
CA (1) CA3070861A1 (en)
WO (1) WO2019060174A1 (en)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3044593A1 (en) 2016-11-22 2018-05-31 TCR2 Therapeutics Inc. Compositions and methods for tcr reprogramming using fusion proteins
US20210079061A1 (en) * 2018-02-26 2021-03-18 Fred Hutchinson Cancer Research Center Compositions and methods for cellular immunotherapy
AU2020265679A1 (en) 2019-04-30 2021-12-23 Senti Biosciences, Inc. Chimeric receptors and methods of use thereof
MX2021013368A (en) * 2019-04-30 2021-11-25 Atara Biotherapeutics Inc T CELLS OF THE RECEPTOR OF CHIMERIC ANTIGENS FOCUSED TO CD19 SPECIFIC OF THE ANTIGEN.
SG10201908256RA (en) * 2019-09-06 2021-04-29 Nat Univ Singapore T cell modified with a synthetic receptor containing a single ITAM signaling motif
CN115087666B (en) * 2020-02-13 2023-10-03 北京艺妙神州医药科技有限公司 Optimization of chimeric antigen receptors
JP2023519970A (en) * 2020-03-31 2023-05-15 フレッド ハッチンソン キャンサー センター Enhanced antigen-negative cell death in antigen-targeted immunotherapy
CN111411085A (en) * 2020-04-10 2020-07-14 格源致善(上海)生物科技有限公司 Chimeric antigen receptor T cell and application thereof
WO2021244654A1 (en) * 2020-06-05 2021-12-09 Nanjing Legend Biotech Co., Ltd. Activation induced cytokine production in immune cells
US20240115608A1 (en) * 2021-02-10 2024-04-11 The Regents Of The University Of California Immune receptors with synthetic co-stimulatory domains
CN113203781B (en) * 2021-05-13 2022-05-31 桂林电子科技大学 Method for detecting GPC3 based on RGO-CS-Hemin @ Pt NPs nano material and aptamer for non-diagnosis purpose
US20250302878A1 (en) * 2022-06-14 2025-10-02 H. Lee Moffitt Cancer Center And Research Institute Inc. Nkg2d expressing car-t cells

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014127261A1 (en) * 2013-02-15 2014-08-21 The Regents Of The University Of California Chimeric antigen receptor and methods of use thereof
US20140328812A1 (en) * 2003-11-05 2014-11-06 St. Jude Children's Research Hospital, Inc. Chimeric receptors with 4-1bb stimulatory signaling domain
EP3336107A1 (en) * 2016-12-15 2018-06-20 Miltenyi Biotec GmbH Immune cells expressing an antigen binding receptor and a chimeric costimulatory receptor

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016014553A1 (en) * 2014-07-21 2016-01-28 Novartis Ag Sortase synthesized chimeric antigen receptors
AU2015305531B2 (en) * 2014-08-19 2021-05-20 Novartis Ag Anti-CD123 chimeric antigen receptor (CAR) for use in cancer treatment

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140328812A1 (en) * 2003-11-05 2014-11-06 St. Jude Children's Research Hospital, Inc. Chimeric receptors with 4-1bb stimulatory signaling domain
WO2014127261A1 (en) * 2013-02-15 2014-08-21 The Regents Of The University Of California Chimeric antigen receptor and methods of use thereof
EP3336107A1 (en) * 2016-12-15 2018-06-20 Miltenyi Biotec GmbH Immune cells expressing an antigen binding receptor and a chimeric costimulatory receptor

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
ADRIENNE H LONG ET AL: "4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors", NATURE MEDICINE, vol. 21, no. 6, 4 May 2015 (2015-05-04), New York, pages 581 - 590, XP055278553, ISSN: 1078-8956, DOI: 10.1038/nm.3838 *
DATABASE Geneseq [online] 9 August 2018 (2018-08-09), "Human 4-1BB intracellular domain, SEQ:21.", XP093123513, retrieved from EBI accession no. GSP:BFJ88468 Database accession no. BFJ88468 *
DIOGO GOMES-SILVA ET AL: "Tonic 4-1BB Costimulation in Chimeric Antigen Receptors Impedes T Cell Survival and Is Vector-Dependent", CELL REPORTS, vol. 21, no. 1, 1 October 2017 (2017-10-01), US, pages 17 - 26, XP055690717, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2017.09.015 *
LI GONGBO ET AL: "4-1BB enhancement of CAR T function requires NF-[kappa]B and TRAFs", JCI INSIGHT, vol. 3, no. 18, 20 September 2018 (2018-09-20), XP093035954, ISSN: 2379-3708, DOI: 10.1172/jci.insight.121322 *
LI GONGBO ET AL: "Mutation of the 41BB co-stimulatory domain enhances CAR signaling and mouse CD19-targeted CAR T cell function", 1 February 2017 (2017-02-01), XP009527374, Retrieved from the Internet <URL:https://www.researchgate.net/publication/314151105_Mutation_of_the_41BB_co-stimulatory_domain_enhances_CAR_signaling_and_mouse_CD19-targeted_CAR_T_cell_function> [retrieved on 20210506], DOI: 10.13140/RG.2.2.14247.75682 *
LI GONGBO ET AL: "Optimization of Murine 4-1BB Signaling Results in Enhanced CD19-Targeted CAR T Cell Function in Immune Competent Mice", BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, vol. 23, no. 3, 1 March 2017 (2017-03-01), XP029931874, ISSN: 1083-8791, DOI: 10.1016/J.BBMT.2016.12.417 *
M. SADELAIN ET AL: "The Basic Principles of Chimeric Antigen Receptor Design", CANCER DISCOVERY, vol. 3, no. 4, 1 April 2013 (2013-04-01), pages 388 - 398, XP055133523, ISSN: 2159-8274, DOI: 10.1158/2159-8290.CD-12-0548 *
M. SADELAIN ET AL: "The Basic Principles of Chimeric Antigen Receptor Design", CANCER DISCOVERY, vol. 3, no. 4, 1 April 2013 (2013-04-01), US, pages 388 - 398, XP055287277, ISSN: 2159-8274, DOI: 10.1158/2159-8290.CD-12-0548 *
POSEY AVERY D ET AL: "Mixed Signals: Alteration of CD28 Signaling Motifs Improves Anti-Tumor Efficacy and Persistence of CAR T Cells", MOLECULAR THERAPY, vol. 5, no. S1, 1 May 2017 (2017-05-01), pages 154 - 154, XP055794713 *
See also references of WO2019060174A1 *

Also Published As

Publication number Publication date
AU2018335266A1 (en) 2020-02-06
JP2021500859A (en) 2021-01-14
EP3684424A1 (en) 2020-07-29
CA3070861A1 (en) 2019-03-28
WO2019060174A1 (en) 2019-03-28

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