AR126199A1 - Métodos para aislar linfocitos infiltrantes de tumores y uso de los mismos - Google Patents

Métodos para aislar linfocitos infiltrantes de tumores y uso de los mismos

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Publication number
AR126199A1
AR126199A1 ARP220101632A ARP220101632A AR126199A1 AR 126199 A1 AR126199 A1 AR 126199A1 AR P220101632 A ARP220101632 A AR P220101632A AR P220101632 A ARP220101632 A AR P220101632A AR 126199 A1 AR126199 A1 AR 126199A1
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Argentina
Prior art keywords
til population
tumor
population
cryopreserved
disaggregated
Prior art date
Application number
ARP220101632A
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English (en)
Inventor
Sunetra Biswas
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Instil Bio Inc
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Publication date
Application filed by Instil Bio Inc filed Critical Instil Bio Inc
Publication of AR126199A1 publication Critical patent/AR126199A1/es

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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
    • A61K2239/57—Skin; melanoma
    • 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
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A61K39/46449—Melanoma antigens
    • G—PHYSICS
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G01N33/505—Cells of the immune system involving T-cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854—Immunoglobulins
    • 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
    • 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
    • C12N5/0635—B lymphocytes
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/52—Assays involving cytokines
    • G01N2333/555—Interferons [IFN]
    • G01N2333/57—IFN-gamma
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Cell Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Veterinary Medicine (AREA)
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  • Mycology (AREA)
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  • Biotechnology (AREA)
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  • Food Science & Technology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
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  • Physics & Mathematics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Tropical Medicine & Parasitology (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hospice & Palliative Care (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

Métodos para determinar la potencia de linfocitos infiltrantes de tumores (TIL) aislados y expandidos y para producir poblaciones terapéuticas de TIL, así como composiciones que los comprenden y métodos de tratamiento con los mismos. Reivindicación 1: Un método para evaluar la potencia de linfocitos infiltrantes de tumores (TIL) contra células cancerosas, caracterizado porque comprende: a) obtener una población aislada y expandida ex vivo de los TIL; b) cocultivar la población de los TIL con células diana modificadas que activan las células T a través de CD3 para preparar una población de TIL activada; c) agregar a la población de TIL activada, un anticuerpo anti-CD107a marcado con fluorescencia o un fragmento de unión a antígeno del mismo, un anticuerpo anti-CD2 marcado con fluorescencia o un fragmento de unión a antígeno del mismo, y un anticuerpo anti-IFN-g marcado con fluorescencia o un fragmento de unión a antígeno del mismo; d) detectar la presencia o ausencia de células T CD2+ viables que expresan uno o ambos entre: a. IFN-g, y b. CD107a; y, e) determinar el porcentaje de potencia de la población de TIL activada. Reivindicación 99: Un método para preparar una población terapéutica de linfocitos infiltrantes de tumores (TIL), caracterizado porque comprende: a) desagregar de manera aséptica un tumor extirpado de un sujeto para preparar de esa manera un producto de tumor desagregado, en donde la desagregación comprende aplicar repetidamente presión física entre 120 y 360 veces por minuto a como máximo 6 N/cm² en presencia de un medio de una solución de enzimas, en donde el tumor está suficientemente desagregado en una suspensión de células como para que el producto de tumor desagregado se pueda criopreservar; b) dentro de las 24 horas de preparar el producto de tumor desagregado, enfriar el producto de tumor desagregado hasta una temperatura de criopreservación adecuada para preparar un producto de tumor desagregado criopreservado; c) guardar el producto de tumor desagregado criopreservado en un estado congelado; d) descongelar el producto de tumor desagregado criopreservado; e) realizar una primera expansión mediante el cultivo del producto de tumor desagregado criopreservado en un medio de cultivo celular que comprende IL-2 para producir una primera población de TIL; f) realizar una segunda expansión mediante cultivo de la primera población de TIL en un medio de cultivo celular con IL-2 adicional, OKT-3 y células presentadoras de antígenos (APC), para producir una segunda población de TIL; y g) criopreservar la segunda población de TIL para preparar una población terapéutica de TIL criopreservada; en donde los pasos (a), (b), (c), (d), (e), (f) y (g) se conducen en un sistema cerrado; h) obtener una muestra de la segunda población de TIL del paso f) o una muestra de la población terapéutica de TIL criopreservada del paso g); i) cocultivar la población de los TIL del paso h) con células del tumor para preparar una población de TIL activada; j) agregar a la población de TIL activada, un anticuerpo anti-CD107a marcado con fluorescencia o un fragmento de unión a antígeno del mismo, un anticuerpo anti-CD2 marcado con fluorescencia o un fragmento de unión a antígeno del mismo, y un anticuerpo anti-IFN-g marcado con fluorescencia o un fragmento de unión a antígeno del mismo k) detectar la presencia o ausencia de células T CD2+ viables que expresan uno o ambos entre: a. IFN-g, y b. CD107a; y, l) determinar el porcentaje de potencia de la población de TIL activada.
ARP220101632A 2021-06-24 2022-06-22 Métodos para aislar linfocitos infiltrantes de tumores y uso de los mismos AR126199A1 (es)

Applications Claiming Priority (1)

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US202163214735P 2021-06-24 2021-06-24

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AR126199A1 true AR126199A1 (es) 2023-09-27

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ARP220101632A AR126199A1 (es) 2021-06-24 2022-06-22 Métodos para aislar linfocitos infiltrantes de tumores y uso de los mismos

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US (1) US20240319172A1 (es)
EP (1) EP4358978A1 (es)
AR (1) AR126199A1 (es)
TW (1) TW202317756A (es)
WO (1) WO2022271881A1 (es)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018081784A1 (en) * 2016-10-31 2018-05-03 H. Lee Moffitt Cancer Center And Research Institute, Inc. Artificial antigen presenting cells for expanding immune cells for immunotherapy
WO2020061429A1 (en) * 2018-09-20 2020-03-26 Iovance Biotherapeutics, Inc. Expansion of tils from cryopreserved tumor samples
CA3164986A1 (en) * 2019-12-20 2021-06-24 Instil Bio (Uk) Limited Devices and methods for isolating tumor infiltrating lymphocytes and uses thereof

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TW202317756A (zh) 2023-05-01
WO2022271881A1 (en) 2022-12-29
EP4358978A1 (en) 2024-05-01
US20240319172A1 (en) 2024-09-26

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