BR112022016657A2 - Células car-t bcma com atividades melhoradas - Google Patents

Células car-t bcma com atividades melhoradas

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Publication number
BR112022016657A2
BR112022016657A2 BR112022016657A BR112022016657A BR112022016657A2 BR 112022016657 A2 BR112022016657 A2 BR 112022016657A2 BR 112022016657 A BR112022016657 A BR 112022016657A BR 112022016657 A BR112022016657 A BR 112022016657A BR 112022016657 A2 BR112022016657 A2 BR 112022016657A2
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Brazil
Prior art keywords
cells
immune cells
engineered
bcma
car
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BR112022016657A
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English (en)
Inventor
Junhui Lin Regina
Panowski Siler
Adolfo Sommer Cesar
John Van Blarcom Thomas
Johnson Sasu Barbra
BALAKUMARAN Arun
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Allogene Therapeutics Inc
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Publication date
Application filed by Allogene Therapeutics Inc filed Critical Allogene Therapeutics Inc
Publication of BR112022016657A2 publication Critical patent/BR112022016657A2/pt

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • C—CHEMISTRY; METALLURGY
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    • 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
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/461—Cellular immunotherapy characterised by the cell type used
    • A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/463—Cellular immunotherapy characterised by recombinant expression
    • A61K39/4631—Chimeric Antigen Receptors [CAR]
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A61K39/464402—Receptors, cell surface antigens or cell surface determinants
    • A61K39/464416—Receptors for cytokines
    • A61K39/464417—Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • 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
    • C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • 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
    • C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C07K14/7151—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for tumor necrosis factor [TNF], for lymphotoxin [LT]
    • 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
    • C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C07K14/7155—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
    • C—CHEMISTRY; METALLURGY
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    • 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
    • C07K16/2878—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 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • 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 A61K39/46
    • A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K39/46 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 A61K39/46
    • A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K39/46 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 A61K39/46
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 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
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • C07K2319/03—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
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
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  • Wood Science & Technology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
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  • Virology (AREA)
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  • Plant Pathology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

CÉLULAS CAR-T BCMA COM ATIVIDADES MELHORADAS. São fornecidas aqui células imunes projetadas que compreendem um receptor de citocina quimérico constitutivamente ativo (CACCR) e um receptor de antígeno quimérico específico de antígeno de maturação de células B (BCMA) (CAR). Também são fornecidas neste documento células imunes projetadas que compreendem um ou mais ácidos nucleicos, por exemplo, um vetor bicistrônico, tal como um vetor viral que codifica os CACCRs e BCMA CARs e células imunes projetadas, por exemplo, células T autólogas ou alogênicas projetadas que expressam CACCRs e BCMA CARs a partir dos ácidos nucleicos. Quando presentes em células imunes manipuladas com receptor de antígeno quimérico (CAR), os CACCRs permitem maior ativação, proliferação, persistência e/ou potência de células imunes. Além disso, são fornecidos aqui métodos de fabricação e uso das células imunes manipuladas descritas neste documento, tais como métodos de tratamento de uma doença ou condição pela administração de pelo menos uma dose apropriada das células a um paciente que sofre da condição.
BR112022016657A 2020-02-24 2021-02-24 Células car-t bcma com atividades melhoradas BR112022016657A2 (pt)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US202062980914P 2020-02-24 2020-02-24
US202063020713P 2020-05-06 2020-05-06
US202063053409P 2020-07-17 2020-07-17
US202063092681P 2020-10-16 2020-10-16
PCT/US2021/019362 WO2021173630A1 (en) 2020-02-24 2021-02-24 Bcma car-t cells with enhanced activities

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BR112022016657A2 true BR112022016657A2 (pt) 2022-12-20

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US (1) US20210260118A1 (pt)
EP (1) EP4110805A1 (pt)
JP (1) JP2023514407A (pt)
KR (1) KR20220145846A (pt)
CN (1) CN115175929A (pt)
AU (1) AU2021227191A1 (pt)
BR (1) BR112022016657A2 (pt)
CA (1) CA3167065A1 (pt)
CO (1) CO2022011684A2 (pt)
IL (1) IL295470A (pt)
MX (1) MX2022010340A (pt)
PE (1) PE20221757A1 (pt)
TW (1) TW202146439A (pt)
WO (1) WO2021173630A1 (pt)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2024517413A (ja) 2021-04-16 2024-04-22 セルジーン コーポレーション 以前に幹細胞移植を受けた患者におけるｔ細胞療法
WO2023081735A1 (en) 2021-11-03 2023-05-11 Celgene Corporation Chimeric antigen receptors specific for b-cell maturation antigen for use in treating myeloma
WO2023147515A1 (en) 2022-01-28 2023-08-03 Juno Therapeutics, Inc. Methods of manufacturing cellular compositions
WO2023220641A2 (en) 2022-05-11 2023-11-16 Juno Therapeutics, Inc. Methods and uses related to t cell therapy and production of same
WO2023220655A1 (en) 2022-05-11 2023-11-16 Celgene Corporation Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy
WO2023230548A1 (en) 2022-05-25 2023-11-30 Celgene Corporation Method for predicting response to a t cell therapy
WO2023230581A1 (en) 2022-05-25 2023-11-30 Celgene Corporation Methods of manufacturing t cell therapies
US20240042030A1 (en) 2022-07-29 2024-02-08 Allogene Therapeutics, Inc. Engineered cells with reduced gene expression to mitigate immune cell recognition
WO2024064600A2 (en) * 2022-09-19 2024-03-28 Allogene Therapeutics Inc. B-cell maturation antigen (bcma) anti-idiotypic antibodies
WO2024097905A1 (en) 2022-11-02 2024-05-10 Celgene Corporation Methods of treatment with t cell therapy and immunomodulatory agent maintenance therapy

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6010613A (en) 1995-12-08 2000-01-04 Cyto Pulse Sciences, Inc. Method of treating materials with pulsed electrical fields
WO2011069004A1 (en) * 2009-12-04 2011-06-09 Quest Diagnostics Investments Incorporated Mpl mutations in jak2 v617f negative patients with myeloproliferative disease
GB201206559D0 (en) 2012-04-13 2012-05-30 Ucl Business Plc Polypeptide
IN2014DN10991A (pt) 2012-05-25 2015-09-25 Cellectis
ES2842212T3 (es) 2015-01-26 2021-07-13 Cellectis Receptores de antígenos quiméricos monocatenarios específicos anti-CLL1 (scCAR) para inmunoterapia contra el cáncer
JP6921001B2 (ja) * 2015-04-13 2021-08-18 ファイザー・インク Ｂ細胞成熟抗原を標的にするキメラ抗原受容体
TWI703159B (zh) * 2015-04-13 2020-09-01 美商輝瑞股份有限公司 Bcma特異性治療性抗體及其用途
KR20230167769A (ko) * 2016-08-26 2023-12-11 베이롤 칼리지 오브 메드신 세포 치료요법을 위한 항상성 활성 사이토킨 수용체
CN111819192A (zh) * 2018-03-02 2020-10-23 艾洛基治疗公司 可诱导的嵌合细胞激素受体
US20200054675A1 (en) * 2018-06-01 2020-02-20 Washington University Suppression of cytokine release syndrome in chimeric antigen receptor cell therapy
PE20211902A1 (es) * 2019-03-01 2021-09-27 Allogene Therapeutics Inc Receptores de citocinas quimericos constitutivamente activos
CN113518785A (zh) * 2019-03-01 2021-10-19 艾洛基治疗公司 携带pd-1胞外域的嵌合细胞因子受体

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EP4110805A1 (en) 2023-01-04
JP2023514407A (ja) 2023-04-05
TW202146439A (zh) 2021-12-16
IL295470A (en) 2022-10-01
KR20220145846A (ko) 2022-10-31
WO2021173630A1 (en) 2021-09-02
CO2022011684A2 (es) 2022-08-30
CA3167065A1 (en) 2021-09-02
AU2021227191A1 (en) 2022-08-25
CN115175929A (zh) 2022-10-11
PE20221757A1 (es) 2022-11-11
MX2022010340A (es) 2022-09-19
US20210260118A1 (en) 2021-08-26

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