ES2372713T3 - Vacuna antitumoral derivada de celulas cd4+ normales modificadas químicamente. - Google Patents

Vacuna antitumoral derivada de celulas cd4+ normales modificadas químicamente. Download PDF

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Publication number
ES2372713T3
ES2372713T3 ES08701232T ES08701232T ES2372713T3 ES 2372713 T3 ES2372713 T3 ES 2372713T3 ES 08701232 T ES08701232 T ES 08701232T ES 08701232 T ES08701232 T ES 08701232T ES 2372713 T3 ES2372713 T3 ES 2372713T3
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cells
lymphocytes
antigens
tumor
cell
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Spanish (es)
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Alexei Kirkin
Karine Dzhandzhugazyan
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Cytovac AS
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Cytovac AS
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0634Cells from the blood or the immune system
    • C12N5/0636T lymphocytes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/10Cellular immunotherapy characterised by the cell type used
    • A61K40/11T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/20Cellular immunotherapy characterised by the effect or the function of the cells
    • A61K40/24Antigen-presenting cells [APC]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/40Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41Vertebrate antigens
    • A61K40/42Cancer antigens
    • A61K40/4267Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0634Cells from the blood or the immune system
    • C12N5/0636T lymphocytes
    • C12N5/0637Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/57Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/572Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 cytotoxic response
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/06Anti-neoplasic drugs, anti-retroviral drugs, e.g. azacytidine, cyclophosphamide
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20Cytokines; Chemokines
    • C12N2501/23Interleukins [IL]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00Coculture with; Conditioned medium produced by
    • C12N2502/11Coculture with; Conditioned medium produced by blood or immune system cells
    • C12N2502/1121Dendritic cells

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Oncology (AREA)
  • Mycology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
ES08701232T 2007-01-03 2008-01-03 Vacuna antitumoral derivada de celulas cd4+ normales modificadas químicamente. Active ES2372713T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0700058.1A GB0700058D0 (en) 2007-01-03 2007-01-03 Anti-tumor vaccine based on normal cells
GB0700058 2007-01-03

Publications (1)

Publication Number Publication Date
ES2372713T3 true ES2372713T3 (es) 2012-01-25

Family

ID=37759205

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ES08701232T Active ES2372713T3 (es) 2007-01-03 2008-01-03 Vacuna antitumoral derivada de celulas cd4+ normales modificadas químicamente.

Country Status (14)

Country Link
US (2) US10023839B2 (https=)
EP (1) EP2102331B1 (https=)
JP (1) JP5452231B2 (https=)
AT (1) ATE522600T1 (https=)
AU (1) AU2008203730B2 (https=)
CY (1) CY1112668T1 (https=)
DK (1) DK2102331T3 (https=)
ES (1) ES2372713T3 (https=)
GB (1) GB0700058D0 (https=)
HR (1) HRP20110899T1 (https=)
PL (1) PL2102331T3 (https=)
PT (1) PT2102331E (https=)
SI (1) SI2102331T1 (https=)
WO (1) WO2008081035A1 (https=)

Families Citing this family (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA200801751A1 (ru) * 2008-08-26 2009-02-27 Петр Генриевич ЛОХОВ Способ получения противоопухолевой вакцины
US8467973B2 (en) * 2009-07-28 2013-06-18 Promising Future, Llc Pairing processes for preparing alloreactive cytotoxic T cells
US8666674B2 (en) 2009-07-28 2014-03-04 Promising Future, Llc Pairing processes for preparing reactive cytotoxic T cells
JP5816627B2 (ja) * 2009-10-27 2015-11-18 イミュニカム・エイビイ 抗原特異的t細胞の増殖のための方法
GB201013443D0 (en) 2010-08-11 2010-09-22 Cytovac As Compositions and methods for producing dendritic cells
US10426740B1 (en) 2010-08-18 2019-10-01 Avm Biotechnology, Llc Compositions and methods to inhibit stem cell and progenitor cell binding to lymphoid tissue and for regenerating germinal centers in lymphatic tissues
MX388325B (es) 2015-05-28 2025-03-19 Kite Pharma Inc Metodos de diagnostico para tratamiento con linfocitos t.
IL295224B2 (en) 2015-05-28 2025-07-01 Kite Pharma Inc Methods of conditioning patients for t cell therapy
EP3364969A4 (en) 2015-10-20 2019-07-10 Kite Pharma, Inc. METHOD FOR THE PRODUCTION OF T CELLS FOR T CELL THERAPY
CN109414455B (zh) 2016-04-01 2023-01-20 凯德药业股份有限公司 Bcma结合分子及其使用方法
KR20200068750A (ko) 2016-04-01 2020-06-15 카이트 파마 인코포레이티드 키메라 수용체 및 그의 사용 방법
PT3436079T (pt) 2016-04-01 2021-10-06 Kite Pharma Inc Recetores de antigénios quiméricos e de células t e métodos de uso
PT3583129T (pt) 2017-02-14 2021-12-14 Kite Pharma Inc Moléculas de ligação a cd70 e seus métodos de uso
WO2018169922A2 (en) 2017-03-13 2018-09-20 Kite Pharma, Inc. Chimeric antigen receptors for melanoma and uses thereof
EP3490605B1 (en) 2017-04-01 2023-06-07 AVM Biotechnology, LLC Replacement of cytotoxic preconditioning before cellular immunotherapy
AU2018250148B2 (en) 2017-04-03 2021-09-23 Kite Pharma, Inc. Treatment using chimeric receptor T cells incorporating optimized polyfunctional T cells
SG10201912400VA (en) 2017-04-24 2020-02-27 Kite Pharma Inc Humanized antigen-binding domains against cd19 and methods of use
TWI862477B (zh) 2017-05-26 2024-11-21 美商凱特製藥公司 製備和使用胚胎間充質先驅細胞的方法
KR20230052312A (ko) 2017-09-15 2023-04-19 카이트 파마 인코포레이티드 관리 연속성 및 신원 연속성 생물학적 샘플 추적으로 환자-특이적 면역요법 절차를 수행하기 위한 방법 및 시스템
CA3076099A1 (en) 2017-09-22 2019-03-28 Kite Pharma, Inc. Linkers for chimeric antigen receptors
CA3084470A1 (en) 2017-10-18 2019-04-25 Kite Pharma, Inc. Methods of administering chimeric antigen receptor immunotherapy
WO2019099707A1 (en) 2017-11-16 2019-05-23 Kite Pharma, Inc Modified chimeric antigen receptors and methods of use
BR112020014446A2 (pt) 2018-01-15 2020-12-29 Pfizer Inc. Métodos para administrar imunoterapia de receptor de antígeno quimérico em combinação com agonista de 4-1bb
WO2019152957A1 (en) 2018-02-02 2019-08-08 Arizona Board Of Regents On Behalf Of Arizona State University Dna-chimeric antigen receptor t cells for immunotherapy
CN112534044A (zh) 2018-02-16 2021-03-19 凯德药业股份有限公司 经修饰的多能干细胞及制备和使用方法
TWI784324B (zh) 2018-04-12 2022-11-21 美商凱特製藥公司 利用腫瘤微環境之特性之嵌合受體t細胞治療
KR102544086B1 (ko) 2018-06-01 2023-06-16 카이트 파마 인코포레이티드 키메라 항원 수용체 t 세포 요법
US20210155941A1 (en) 2018-06-22 2021-05-27 Kite Pharma Eu B.V. Compositions and methods for making engineered t cells
SG11202101014XA (en) 2018-08-02 2021-02-25 Kite Pharma Inc Chimeric antigen receptor therapy t cell expansion kinetics and uses thereof
EP3488851A1 (en) 2018-10-03 2019-05-29 AVM Biotechnology, LLC Immunoablative therapies
EP3632446B3 (en) 2018-10-03 2024-01-24 AVM Biotechnology, LLC Immunoablative therapies
KR102840400B1 (ko) 2018-12-12 2025-08-04 카이트 파마 인코포레이티드 키메라 항원 수용체 및 car-t 세포 및 사용 방법
US20220175900A1 (en) * 2019-04-12 2022-06-09 Cytovac A/S Method for preparation of cancer/testis antigen-specific t-cells
US20200384027A1 (en) 2019-05-03 2020-12-10 Kite Pharma, Inc. Methods of administering chimeric antigen receptor immunotherapy
WO2020257823A2 (en) 2019-06-21 2020-12-24 Kite Pharma, Inc. TGF-β RECEPTORS AND METHODS OF USE
KR20220054383A (ko) 2019-09-03 2022-05-02 알로젠 테라퓨틱스 인코포레이티드 T 세포 요법을 위한 t 세포를 제조하는 방법
IL292665B2 (en) 2019-11-06 2026-02-01 Kite Pharma Inc Chimeric antigen receptor T cell therapy
US20230293530A1 (en) 2020-06-24 2023-09-21 Yeda Research And Development Co. Ltd. Agents for sensitizing solid tumors to treatment
KR20230084470A (ko) 2020-08-14 2023-06-13 카이트 파마 인코포레이티드 면역 세포 기능의 향상
US12152251B2 (en) 2020-08-25 2024-11-26 Kite Pharma, Inc. T cells with improved functionality
US20220155299A1 (en) 2020-10-28 2022-05-19 Kite Pharma, Inc. Flow cytometric method for characterization of t-cell impurities
AU2021410635A1 (en) 2020-12-24 2023-06-29 Kite Pharma, Inc. Prostate cancer chimeric antigen receptors
WO2022150582A1 (en) 2021-01-10 2022-07-14 Kite Pharma, Inc. T cell therapy
EP4281545A1 (en) 2021-01-21 2023-11-29 CytoVac A/S Method for t-cell expansion and related medical applications
TW202241469A (zh) 2021-02-20 2022-11-01 美商凱特製藥公司 免疫療法
IL305571A (en) 2021-03-11 2023-10-01 Kite Pharma Inc Improving the function of immune system cells
AU2022259428A1 (en) 2021-04-16 2023-10-26 Kite Pharma, Inc. Taci/bcma dual binding molecules
WO2022221126A1 (en) 2021-04-16 2022-10-20 Kite Pharma, Inc. Methods and systems for scheduling a patient-specific immunotherapy procedure
EP4337227A2 (en) 2021-05-14 2024-03-20 Kite Pharma, Inc. Chimeric antigen receptor t cell therapy
IL308696A (en) 2021-05-24 2024-01-01 Kite Pharma Inc Nkg2d-based chimeric antgen receptor
WO2022261061A1 (en) 2021-06-08 2022-12-15 Kite Pharma, Inc. Gpc3 binding molecules
WO2022269019A1 (en) 2021-06-25 2022-12-29 Cytovac A/S Method for preparation of cytotoxic t lymphocytes with broad tumour-specific reactivity and characteristics of early differentiation cells
WO2023278553A1 (en) 2021-07-01 2023-01-05 Kite Pharma, Inc. Closed-system and method for autologous and allogeneic cell therapy manufacturing
JP2024525485A (ja) 2021-07-02 2024-07-12 カイト ファーマ インコーポレイテッド 細胞療法適用において使用される遺伝子構築物由来の遺伝子産物におけるバリアントを特定するための方法
WO2023009989A1 (en) 2021-07-26 2023-02-02 Kite Pharma, Inc. Split chimeric antigen receptors and methods of use
US20230268031A1 (en) 2021-07-30 2023-08-24 Kite Pharma, Inc. Monitoring and management of cell therapy-induced toxicities
TWI863006B (zh) 2021-10-18 2024-11-21 美商凱特製藥公司 用於嵌合抗原受體之信號傳導域
US20230296610A1 (en) 2022-02-15 2023-09-21 Kite Pharma, Inc. Predicting adverse events from immunotherapy
WO2023247324A1 (en) 2022-06-24 2023-12-28 Cytovac A/S Novel combination treatment with adoptive cellular therapy
US20240091261A1 (en) 2022-08-26 2024-03-21 Kite Pharma, Inc. Immune cell function
KR20250097844A (ko) 2022-10-28 2025-06-30 카이트 파마 인코포레이티드 면역요법의 효능 향상 및 지속적인 반응
WO2024092227A1 (en) 2022-10-28 2024-05-02 Kite Pharma, Inc. Factors for optimizing immunotherapy
KR20250162836A (ko) 2023-03-17 2025-11-19 카이트 파마 인코포레이티드 종양 미세환경이 면역요법의 효능에 미치는 영향
WO2025096517A1 (en) 2023-11-01 2025-05-08 Kite Pharma, Inc. Factors for optimizing immunotherapy efficacy
US20250262300A1 (en) 2024-02-16 2025-08-21 Kite Pharma, Inc. Systems, methods, and kits for generating and administering engineered t cells and cd38 targeting compounds as a combination therapy
WO2025188561A1 (en) 2024-03-04 2025-09-12 Kite Pharma, Inc. Predictive markers for immunotherapy
WO2025231376A1 (en) 2024-05-03 2025-11-06 Kite Pharma, Inc. Chimeric receptors binding to cll-1 and methods of use thereof
WO2025250819A1 (en) 2024-05-31 2025-12-04 Kite Pharma, Inc. Tricistronic constructs for anti-gpc3 car
US20260009001A1 (en) 2024-07-08 2026-01-08 Kite Pharma, Inc. Systems and methods for applying mechanical force to living cells to generate a phenotypic response

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003012085A1 (en) * 2001-07-30 2003-02-13 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Antigen presenting cells, method for their preparation and their use for cancer vaccines

Also Published As

Publication number Publication date
JP5452231B2 (ja) 2014-03-26
US10023839B2 (en) 2018-07-17
PT2102331E (pt) 2011-12-19
WO2008081035A1 (en) 2008-07-10
HRP20110899T1 (hr) 2011-12-31
US20180036397A1 (en) 2018-02-08
CY1112668T1 (el) 2016-02-10
PL2102331T3 (pl) 2012-01-31
AU2008203730B2 (en) 2013-11-07
EP2102331A1 (en) 2009-09-23
DK2102331T3 (da) 2011-10-17
AU2008203730A1 (en) 2008-07-10
JP2010514455A (ja) 2010-05-06
SI2102331T1 (sl) 2012-01-31
EP2102331B1 (en) 2011-08-31
ATE522600T1 (de) 2011-09-15
GB0700058D0 (en) 2007-02-07
US20100092498A1 (en) 2010-04-15

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