RU2018140694A - ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА - Google Patents
ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА Download PDFInfo
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- RU2018140694A RU2018140694A RU2018140694A RU2018140694A RU2018140694A RU 2018140694 A RU2018140694 A RU 2018140694A RU 2018140694 A RU2018140694 A RU 2018140694A RU 2018140694 A RU2018140694 A RU 2018140694A RU 2018140694 A RU2018140694 A RU 2018140694A
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- trbc1
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- 239000000427 antigen Substances 0.000 title claims 8
- 102000036639 antigens Human genes 0.000 title claims 8
- 108091007433 antigens Proteins 0.000 title claims 8
- 241000251204 Chimaeridae Species 0.000 title 1
- 108091008874 T cell receptors Proteins 0.000 title 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 title 1
- 230000000890 antigenic effect Effects 0.000 title 1
- 108020003175 receptors Proteins 0.000 title 1
- 238000000034 method Methods 0.000 claims 15
- 101000662909 Homo sapiens T cell receptor beta constant 1 Proteins 0.000 claims 11
- 101000662902 Homo sapiens T cell receptor beta constant 2 Proteins 0.000 claims 11
- 102100037272 T cell receptor beta constant 1 Human genes 0.000 claims 11
- 102100037298 T cell receptor beta constant 2 Human genes 0.000 claims 11
- 210000001744 T-lymphocyte Anatomy 0.000 claims 10
- 238000002560 therapeutic procedure Methods 0.000 claims 5
- 208000000389 T-cell leukemia Diseases 0.000 claims 4
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 claims 4
- 206010042971 T-cell lymphoma Diseases 0.000 claims 4
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims 4
- 230000003211 malignant effect Effects 0.000 claims 4
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims 2
- 238000001574 biopsy Methods 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 210000005259 peripheral blood Anatomy 0.000 claims 2
- 239000011886 peripheral blood Substances 0.000 claims 2
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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
- C07K16/2809—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 against the T-cell receptor (TcR)-CD3 complex
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- 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]
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- 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]
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- 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
- A61K39/464411—Immunoglobulin superfamily
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- 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
- A61K39/464838—Viral antigens
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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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
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
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- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57426—Specifically defined cancers leukemia
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- 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
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- 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)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- 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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- 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
- G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
- G01N2333/7051—T-cell receptor (TcR)-CD3 complex
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Claims (23)
1. Способ диагностики Т-клеточной лимфомы или лейкемии у индивидуума, который включает этап определения процента T-клеток, которые являются TRBC1- или TRBC2-положительными, от общего числа T-клеток в образце, выделенного у индивидуума.
2. Способ по п. 1, где процент TRBC1- или TRBC2-положительных T-клеток, который составляет больше чем приблизительно 80%, указывает на наличие Т-клеточной лимфомы или лейкемии.
3. Способ по п. 1 или 2, где образец представляет собой образец периферической крови или биопсию.
4. Способ по любому из пп. 1-3, где общее число T-клеток выявляют в образце или выделяют из образца с использованием агента, который связывается с CD3.
5. Способ по любому из пп. 1-4, где стадию определения процента T-клеток, которые являются TRBC1- или TRBC2-положительными, от общего числа T-клеток в образце, выделенного у индивидуума, осуществляют с использованием средства, которое содержит антигенсвязывающий домен, который селективно связывается с константной областью 1 TCR бета (TRBC1) или TRBC2.
6. Способ отбора подходящей терапии для лечения индивидуума, страдающего от Т-клеточной лимфомы или лейкемии, где способ включает стадии:
i) определения наличия экспрессии TRBC1 или TRBC2 злокачественной T-клеткой у индивидуума; и
ii) отбора терапии, основываясь на экспрессии TRBC1 или TRBC2 злокачественной T-клеткой, где указанная терапия основана на выделенной клетке, содержащей химерный антигенный рецептор (CAR), который содержит антигенсвязывающий домен, который селективно связывается с TRBC1 или TRBC2.
7. Способ отбора индивидуума, страдающего от Т-клеточной лимфомы или лейкемии, для прохождения терапии, основанной на выделенной клетки, содержащей CAR, который содержит антигенсвязывающий домен, который селективно связывается с TRBC1 или TRBC2, где способ включает стадии:
i) определения наличия экспрессии TRBC1 или TRBC2 злокачественной T-клеткой у индивидуума; и
ii) отбор указанного индивидуума для прохождения указанной терапии, основанной на экспрессии TRBC1 или TRBC2 указанной злокачественной T-клеткой.
8. Способ по любому из пп. 6 или 7, где образец представляет собой образец периферической крови или биопсию.
9. Способ по любому из пп.1-8, где антигенсвязывающий домен селективно связывается с TRBC1.
10. Способ по 9, где антигенсвязывающий домен имеет вариабельную тяжелую цепь (VH) и вариабельную легкую цепь (VL), которые содержат следующие определяющие комплементарность области (CDR):
VH CDR1: SEQ ID No. 7;
VH CDR2: SEQ ID No. 8;
VH CDR3: SEQ ID No. 9;
VL CDR1: SEQ ID No. 10;
VL CDR2: SEQ ID No. 11; и
VL CDR3: SEQ ID No. 12.
11. Способ по 9, где антигенсвязывающий домен содержит вариабельную тяжелую цепь (VH), имеющую аминокислотную последовательность SEQ ID No. 1, и вариабельную легкую цепь (VL), имеющую аминокислотную последовательность SEQ ID No. 2.
12. Способ по 9, где антигенсвязывающий домен содержит scFv с аминокислотной последовательностью SEQ ID No. 3.
13. Способ по любому из пп.1-8, при котором селективно связывается TRBC2.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1403905.1 | 2014-03-05 | ||
| GB201403905A GB201403905D0 (en) | 2014-03-05 | 2014-03-05 | Method |
| GB1416908.0 | 2014-09-25 | ||
| GB201416908A GB201416908D0 (en) | 2014-09-25 | 2014-09-25 | Method |
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| Application Number | Title | Priority Date | Filing Date |
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| RU2016138421A Division RU2744046C2 (ru) | 2014-03-05 | 2015-03-05 | ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА |
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| RU2018140694A RU2018140694A (ru) | 2014-03-05 | 2015-03-05 | ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА |
| RU2021101502A RU2021101502A (ru) | 2014-03-05 | 2015-03-05 | ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА |
| RU2016138421A RU2744046C2 (ru) | 2014-03-05 | 2015-03-05 | ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА |
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| RU2016138421A RU2744046C2 (ru) | 2014-03-05 | 2015-03-05 | ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА |
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| US (2) | US20170066827A1 (ru) |
| EP (2) | EP3241561A1 (ru) |
| JP (5) | JP6767872B2 (ru) |
| KR (3) | KR102088082B1 (ru) |
| CN (3) | CN106068276B (ru) |
| AU (3) | AU2015225944B2 (ru) |
| BR (1) | BR112016020304B1 (ru) |
| CA (1) | CA2940564C (ru) |
| CL (4) | CL2016002195A1 (ru) |
| CU (1) | CU24475B1 (ru) |
| DK (1) | DK3125934T3 (ru) |
| ES (1) | ES2758173T3 (ru) |
| HU (1) | HUE047641T2 (ru) |
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| MX (3) | MX2016010856A (ru) |
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| PH (2) | PH12016501646A1 (ru) |
| PL (1) | PL3125934T3 (ru) |
| PT (1) | PT3125934T (ru) |
| RU (3) | RU2018140694A (ru) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11885807B2 (en) | 2014-03-05 | 2024-01-30 | Autolus Limited | Method for depleting malignant T-cells |
| US11385233B2 (en) | 2015-03-05 | 2022-07-12 | Autolus Limited | Methods of depleting malignant T-cells |
| GB201403972D0 (en) | 2014-03-06 | 2014-04-23 | Ucl Business Plc | Chimeric antigen receptor |
| WO2016051205A1 (en) * | 2014-10-03 | 2016-04-07 | Isis Innovation Limited | Analysis of t-cell monotypia |
| CA2937157A1 (en) * | 2016-07-25 | 2018-01-25 | Ucl Business Plc | Protein-based t-cell receptor knockdown |
| AU2018219887B2 (en) | 2017-02-08 | 2024-08-15 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins for activation of natural killer cells and therapeutic uses thereof to treat cancer |
| EP4273258A3 (en) | 2017-02-20 | 2024-01-17 | Dragonfly Therapeutics, Inc. | Proteins binding her2, nkg2d and cd16 |
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