RU2017125531A - Химерные антигенные рецепторы и способы их применения - Google Patents

Химерные антигенные рецепторы и способы их применения Download PDF

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RU2017125531A
RU2017125531A RU2017125531A RU2017125531A RU2017125531A RU 2017125531 A RU2017125531 A RU 2017125531A RU 2017125531 A RU2017125531 A RU 2017125531A RU 2017125531 A RU2017125531 A RU 2017125531A RU 2017125531 A RU2017125531 A RU 2017125531A
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car according
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Уэйн А. МАРАСКО
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Дана-Фарбер Кэнсер Инститьют, Инк.
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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    • 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
    • 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
    • C07K14/70535—Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
    • 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
    • C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], 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
    • C07K16/2827—Immunoglobulins [IG], 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 against B7 molecules, e.g. CD80, CD86
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • 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

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  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Preparation Of Compounds By Using Micro-Organisms (AREA)
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  • Pharmacology & Pharmacy (AREA)
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Claims (21)

1. Химерный антигенный рецептор (CAR), содержащий внутриклеточный сигнальный домен, трансмембранный домен и внеклеточный домен.
2. CAR по п.1, где трансмембранный домен дополнительно содержит стеблевую область, расположенную между внеклеточным доменом и трансмембранным доменом.
3. CAR по п.1, где трансмембранный домен содержит CD28.
4. CAR по п.1, дополнительно содержащий один или несколько дополнительных костимуляторных мМолекул, расположенных между трансмембранным доменом и внутриклеточным сигнальным доменом.
5. CAR по п.4, где костимуляторными молекулами являются CD28, 4-1BB, ICOS или OX40.
6. CAR по п.1, где внутриклеточный сигнальный домен содержит дзету-цепь CD3.
7. CAR по п.1, где внеклеточный домен представляет собой антитело.
8. CAR по п.7, где антитело представляет собой Fab или scFV.
9. CAR по п.7, где антитело является специфичным в отношении BCMA, CD138, CCR4, PD-1, PDL-1, PD-L2, CXCR4, GITR, вируса SARS, флавивируса, вируса MERS, вируса гриппа или CAIX.
10. Нуклеиновая кислота, кодирующая CAR по любому одному из предшествующих пп., дополнительно содержащая нуклеиновую кислоту, кодирующую полипептид, расположенный после внутриклеточного сигнального домена.
11. Нуклеиновая кислота по п.10, где полипептид представляет собой антитело.
12. Нуклеиновая кислота по п.11, где антитело представляет собой scFV.
13. Нуклеиновая кислота по п.12, где антитело является специфичным в отношении BCMA, CD138, CCR4, PD-1, PDL-1, PD-L2, CXCR4, GITR, вируса SARS, флавивируса, вируса MERS, вируса гриппа или CAIX.
14. Вектор, содержащий нуклеиновую кислоту по любому одному из пп.11-13.
15. Клетка, содержащая вектор по п.14.
16. Генетически сконструированная клетка, которая экспрессирует и несет на поверхности клеточной мембраны химерный антигенный рецептор по любому одному из пп.1-9.
17. Генетически сконструированная клетка по п.16, где клетка представляет собой Т-клетку или NK-клетку.
18. Генетически сконструированная клетка по п.17, где Т-клетка является CD4+ или CD8+.
19. Генетически сконструированная клетка по п.18, которая содержит смешанную популяцию CD4+ и CD8+ клеток.
20. Клетка по п.16, где клетка дополнительно генетически модифицирована для экспрессии и секреции полипептида.
21. Клетка по п.20, где экспрессируемым и секретируемым полипептидом является анти-PDL-1.
RU2017125531A 2014-12-19 2015-12-21 Химерные антигенные рецепторы и способы их применения RU2017125531A (ru)

Applications Claiming Priority (5)

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US201462094625P 2014-12-19 2014-12-19
US62/094,625 2014-12-19
US201562252083P 2015-11-06 2015-11-06
US62/252,083 2015-11-06
PCT/US2015/067225 WO2016100985A2 (en) 2014-12-19 2015-12-21 Chimeric antigen receptors and methods of use thereof

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US (3) US20170362297A1 (ru)
EP (1) EP3233900A2 (ru)
JP (3) JP2018504894A (ru)
KR (2) KR102923234B1 (ru)
CN (1) CN108064252A (ru)
AU (4) AU2015364245B2 (ru)
BR (1) BR112017013176A2 (ru)
CA (1) CA2968412A1 (ru)
IL (3) IL320860A (ru)
RU (1) RU2017125531A (ru)
WO (1) WO2016100985A2 (ru)

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