RU2015140624A - Т-клетки, перенацеленные в отношении cd123-специфичного химерного антигенного рецептора, и способы их применения - Google Patents
Т-клетки, перенацеленные в отношении cd123-специфичного химерного антигенного рецептора, и способы их применения Download PDFInfo
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- 210000001744 T-lymphocyte Anatomy 0.000 title claims 5
- 238000000034 method Methods 0.000 title claims 3
- 230000000890 antigenic effect Effects 0.000 title claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 24
- 238000006467 substitution reaction Methods 0.000 claims 22
- 108020004707 nucleic acids Proteins 0.000 claims 9
- 102000039446 nucleic acids Human genes 0.000 claims 9
- 150000007523 nucleic acids Chemical class 0.000 claims 9
- 229920001184 polypeptide Polymers 0.000 claims 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims 6
- 239000002773 nucleotide Substances 0.000 claims 5
- 125000003729 nucleotide group Chemical group 0.000 claims 5
- 108091008874 T cell receptors Proteins 0.000 claims 4
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims 4
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims 3
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims 2
- 239000013603 viral vector Substances 0.000 claims 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims 1
- 102100027207 CD27 antigen Human genes 0.000 claims 1
- 102000004039 Caspase-9 Human genes 0.000 claims 1
- 108090000566 Caspase-9 Proteins 0.000 claims 1
- 102000001301 EGF receptor Human genes 0.000 claims 1
- 108060006698 EGF receptor Proteins 0.000 claims 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims 1
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims 1
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
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Claims (14)
1. Молекула нуклеиновой кислоты, кодирующая полипептид химерного антигенного рецептора CD123 (CD123CAR), включающий анти-CD123-scFv-область, модифицированную шарнирную областью IgG, содержащую одну или более аминокислотную замену, выбранную из группы, состоящей из аминокислотной замены S228P, аминокислотной замены L235E и аминокислотной замены N297Q, трансмембранный домен и сигнальный домен дзета-цепи Т-клеточного рецептора (TCR).
2. Молекула нуклеиновой кислоты по п. 1, где модифицированная шарнирная область IgG содержит аминокислотную замену L235E и аминокислотную замену N297Q.
3. Молекула нуклеиновой кислоты по п. 1, где модифицированная шарнирная область IgG выбрана из группы, состоящей из модифицированная шарнирная область IgG1, модифицированная шарнирная область IgG2, модифицированная шарнирная область IgG3 и модифицированная шарнирная область IgG4.
4. Молекула нуклеиновой кислоты по п. 1, где анти-CD123-scFv-область является гуманизированной.
5. Молекула нуклеиновой кислоты по п. 1, где полипептид CD123CAR также содержит по меньшей мере один костимуляторный сигнальный домен, выбранный среди костимуляторного сигнального домена CD27, костимуляторного сигнального домена CD28, костимуляторного сигнального домена 4-1ВВ, костимуляторного сигнального домена ОХ40 или любой их комбинации.
6. Молекула нуклеиновой кислоты по п. 1, где трансмембранный домен представляет собой модифицированный трансмембранный домен CD28.
7. Молекула нуклеиновой кислоты по п. 1, где модифицированная шарнирная область IgG содержит аминокислотную последовательность SEQ ID NO: 13, имеющую одну или более аминокислотную замену, выбранную из группы, состоящей из аминокислотной замены S228P, аминокислотной замены L235E и аминокислотной замены N297Q.
8. Молекула нуклеиновой кислоты по п. 1, где полипептид CD123CAR содержит аминокислотную последовательность, выбранную из группы, состоящей из: SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 и SEQ ID NO: 12.
9. Молекула нуклеиновой кислоты по п. 1, содержащая нуклеотидную последовательность, выбранную из группы, состоящей из: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 и SEQ ID NO: 4.
10. Экспрессионная кассета, содержащая нуклеотидную последовательность, кодирующую полипептид химерного антигенного рецептора CD123 (CD123CAR), включающий анти-CD123-scFv-область, модифицированную шарнирную областью IgG, содержащую одну или более аминокислотную замену, выбранную из группы, состоящей из аминокислотной замены S228P, аминокислотной замены L235E и аминокислотной замены N297Q, и сигнальный домен дзета-цепи Т-клеточного рецептора (TCR).
11. Экспрессионная кассета по п. 10, дополнительно содержащая нуклеотидную последовательность, кодирующую вспомогательный ген, выбранный из группы, состоящей из: усеченного рецептора эпидермального фактора роста EGFR (EGFRt), усеченного CD19 (CD19t) или каспазы 9.
12. Популяция человеческих Т-клеток, трансдуцированных вирусным вектором, содержащим экспрессионную кассету, содержащую нуклеотидную последовательность, кодирующую полипептид химерного антигенного рецептора CD123 (CD123CAR), включающий анти-CD123-scFv-область, модифицированную шарнирную областью IgG, содержащую одну или более аминокислотную замену, выбранную из группы, состоящей из аминокислотной замены S228P, аминокислотной замены L235E и аминокислотной замены N297Q, и сигнальный домен дзета-цепи Т-клеточного рецептора (TCR).
13. Способ лечения острого миелоидного лейкоза (AML) у субъекта, включающий введение субъекту популяции Т-клеток, трансдуцированных вирусным вектором, содержащим экспрессионную кассету, содержащую нуклеотидную последовательность, кодирующую полипептид химерного антигенного рецептора CD123 (CD123CAR), включающий анти-CD123-scFv-область, модифицированную шарнирную областью IgG, содержащую одну или более аминокислотную замену, выбранную из группы, состоящей из аминокислотной замены S228P, аминокислотной замены L235E и аминокислотной замены N297Q, и сигнальный домен дзета-цепи Т-клеточного рецептора (TCR).
14. Способ по п. 13, где Т-клетки являются аутологичными Т-клетками.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/844,048 US9657105B2 (en) | 2013-03-15 | 2013-03-15 | CD123-specific chimeric antigen receptor redirected T cells and methods of their use |
| US13/844,048 | 2013-03-15 | ||
| PCT/US2014/029109 WO2014144622A2 (en) | 2013-03-15 | 2014-03-14 | Cd123-specific chimeric antigen receptor redirected t cells and methods of their use |
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| Publication Number | Publication Date |
|---|---|
| RU2015140624A true RU2015140624A (ru) | 2017-04-26 |
| RU2711114C2 RU2711114C2 (ru) | 2020-01-15 |
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| US (3) | US9657105B2 (ru) |
| EP (2) | EP2968415B1 (ru) |
| JP (4) | JP6588004B2 (ru) |
| KR (4) | KR102416258B1 (ru) |
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| AU (3) | AU2014228911A1 (ru) |
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| CA (1) | CA2907216C (ru) |
| DK (1) | DK2968415T3 (ru) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| ES2949648T3 (es) | 2012-12-20 | 2023-10-02 | Purdue Research Foundation | Células T que expresan un receptor antigénico quimérico como terapia contra el cáncer |
| WO2014130635A1 (en) | 2013-02-20 | 2014-08-28 | Novartis Ag | Effective targeting of primary human leukemia using anti-cd123 chimeric antigen receptor engineered t cells |
| US9657105B2 (en) | 2013-03-15 | 2017-05-23 | City Of Hope | CD123-specific chimeric antigen receptor redirected T cells and methods of their use |
| UY35468A (es) | 2013-03-16 | 2014-10-31 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico de antígeno anti-cd19 |
| EP3783098A1 (en) | 2013-05-14 | 2021-02-24 | Board Of Regents, The University Of Texas System | Human application of engineered chimeric antigen receptor (car) t-cells |
| SG11201509609SA (en) | 2013-05-24 | 2015-12-30 | Univ Texas | Chimeric antigen receptor-targeting monoclonal antibodies |
| WO2015010096A1 (en) | 2013-07-18 | 2015-01-22 | Baylor College Of Medicine | Method of enhancing potency of immune cells |
| ES2767423T3 (es) * | 2014-01-13 | 2020-06-17 | Hope City | Receptores de antígenos quiméricos (CARS) con mutaciones en la región del espaciador Fc y métodos para su uso |
| WO2015120187A1 (en) | 2014-02-05 | 2015-08-13 | The University Of Chicago | Chimeric antigen receptors recognizing cancer-spevific tn glycopeptide variants |
| KR102375998B1 (ko) * | 2014-02-14 | 2022-03-21 | 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 | 키메라 항원 수용체 및 제조방법 |
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| AU2005213324B2 (en) | 2004-02-06 | 2011-06-09 | Biogen Idec Ma Inc. | Methods and compositions for treating tumors and metastatic disease |
| WO2008127735A1 (en) | 2007-04-13 | 2008-10-23 | Stemline Therapeutics, Inc. | Il3ralpha antibody conjugates and uses thereof |
| PL2250279T3 (pl) | 2008-02-08 | 2016-11-30 | Przeciwciała anty-ifnar1 o zmniejszonym powinowactwie do liganda fc | |
| CA2735456C (en) | 2008-08-26 | 2021-11-16 | City Of Hope | Method and compositions for enhanced anti-tumor effector functioning of t cells |
| CA2750533A1 (en) | 2009-01-23 | 2010-07-29 | Biogen Idec Ma Inc. | Stabilized fc polypeptides with reduced effector function and methods of use |
| DK2496698T3 (en) * | 2009-11-03 | 2019-04-15 | Hope City | TRUNCATED EPIDERIMAL GROWTH FACTOR RECEPTOR (EGFRt) FOR TRUNCATED T-CELL SELECTION |
| ES2754394T3 (es) | 2010-09-08 | 2020-04-17 | Chemotherapeutisches Forschungsinstitut Georg Speyer Haus | Receptores de antígenos quiméricos con una región bisagra optimizada |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| JP6141834B2 (ja) * | 2011-06-06 | 2017-06-07 | ノヴォ ノルディスク アー／エス | 治療抗体 |
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| SG11201404285VA (en) | 2012-02-22 | 2014-10-30 | Univ Pennsylvania | Compositions and methods for generating a persisting population of t cells useful for the treatment of cancer |
| WO2014130635A1 (en) | 2013-02-20 | 2014-08-28 | Novartis Ag | Effective targeting of primary human leukemia using anti-cd123 chimeric antigen receptor engineered t cells |
| US9657105B2 (en) | 2013-03-15 | 2017-05-23 | City Of Hope | CD123-specific chimeric antigen receptor redirected T cells and methods of their use |
| UY35468A (es) | 2013-03-16 | 2014-10-31 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico de antígeno anti-cd19 |
| ES2767423T3 (es) | 2014-01-13 | 2020-06-17 | Hope City | Receptores de antígenos quiméricos (CARS) con mutaciones en la región del espaciador Fc y métodos para su uso |
| IL292650B2 (en) | 2014-09-19 | 2024-04-01 | Hope City | COSTIMULATORY CHIMERIC ANTIGEN RECEPTOR T CELLS TARGETING IL13Ra2 |
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