JP2018518974A5 - - Google Patents
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- JP2018518974A5 JP2018518974A5 JP2017567178A JP2017567178A JP2018518974A5 JP 2018518974 A5 JP2018518974 A5 JP 2018518974A5 JP 2017567178 A JP2017567178 A JP 2017567178A JP 2017567178 A JP2017567178 A JP 2017567178A JP 2018518974 A5 JP2018518974 A5 JP 2018518974A5
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- 239000000427 antigen Substances 0.000 claims 32
- 102000038129 antigens Human genes 0.000 claims 32
- 108091007172 antigens Proteins 0.000 claims 32
- 102100008794 TNFRSF17 Human genes 0.000 claims 21
- 210000004027 cells Anatomy 0.000 claims 19
- 229920001184 polypeptide Polymers 0.000 claims 19
- 101710030909 TNFRSF13B Proteins 0.000 claims 17
- 102100009744 TNFRSF13B Human genes 0.000 claims 17
- -1 LeY Proteins 0.000 claims 15
- 101710038604 TNFRSF17 Proteins 0.000 claims 14
- 102100005826 CD19 Human genes 0.000 claims 13
- 101700087100 CD19 Proteins 0.000 claims 13
- 102100000189 CD22 Human genes 0.000 claims 13
- 101700020617 CD22 Proteins 0.000 claims 13
- 102100003279 CD38 Human genes 0.000 claims 12
- 101700044948 CD38 Proteins 0.000 claims 12
- 102000018109 Glypican-3 Human genes 0.000 claims 12
- 108050007237 Glypican-3 Proteins 0.000 claims 12
- 102100010587 SDC1 Human genes 0.000 claims 12
- 101700070405 SDC1 Proteins 0.000 claims 12
- 102000013529 alpha-Fetoproteins Human genes 0.000 claims 12
- 108010026331 alpha-Fetoproteins Proteins 0.000 claims 12
- 230000000139 costimulatory Effects 0.000 claims 12
- 102100016493 CD33 Human genes 0.000 claims 11
- 101700017647 CD33 Proteins 0.000 claims 11
- 102100018760 IL3RA Human genes 0.000 claims 11
- 101700029869 IL3RA Proteins 0.000 claims 11
- 102100005828 CD5 Human genes 0.000 claims 10
- 101700066525 CD5 Proteins 0.000 claims 10
- 101710030372 CLSTN1 Proteins 0.000 claims 10
- 101710038812 CS1 Proteins 0.000 claims 10
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims 10
- 101710021997 ITPRID2 Proteins 0.000 claims 10
- 102100000165 MS4A1 Human genes 0.000 claims 10
- 101710010909 MS4A1 Proteins 0.000 claims 10
- 102100017640 SLAMF7 Human genes 0.000 claims 10
- 101710030435 SLAMF7 Proteins 0.000 claims 10
- 101700036918 XMT1 Proteins 0.000 claims 10
- 101710029131 rpsA Proteins 0.000 claims 10
- 101710041788 ygbT Proteins 0.000 claims 10
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-N-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-N,1-N-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims 7
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims 7
- 108060000228 ADRM1 Proteins 0.000 claims 6
- 102100016549 ANPEP Human genes 0.000 claims 6
- 101710028178 ANPEP Proteins 0.000 claims 6
- 101700027514 CD14 Proteins 0.000 claims 6
- 102100003268 CD14 Human genes 0.000 claims 6
- 102100005833 CD68 Human genes 0.000 claims 6
- 102100001891 CTAG1A Human genes 0.000 claims 6
- 101710004449 CTAG1A Proteins 0.000 claims 6
- 102100015540 FCGR1A Human genes 0.000 claims 6
- 101710003440 FCGR1A Proteins 0.000 claims 6
- 101710009074 FLT3 Proteins 0.000 claims 6
- 102100019327 FUT4 Human genes 0.000 claims 6
- 101700004786 FUT4 Proteins 0.000 claims 6
- 102100008185 IL6R Human genes 0.000 claims 6
- 101710044247 ITGA2B Proteins 0.000 claims 6
- 102100019332 ITGA2B Human genes 0.000 claims 6
- 102100001477 ITGB3 Human genes 0.000 claims 6
- 101710006664 ITGB3 Proteins 0.000 claims 6
- 108010038501 Interleukin-6 Receptors Proteins 0.000 claims 6
- 102100016985 KIT Human genes 0.000 claims 6
- 101710009391 KIT Proteins 0.000 claims 6
- 210000001744 T-Lymphocytes Anatomy 0.000 claims 6
- 101710030862 TNFRSF13C Proteins 0.000 claims 6
- 102100009743 TNFRSF13C Human genes 0.000 claims 6
- 230000011664 signaling Effects 0.000 claims 6
- 102100013077 CD4 Human genes 0.000 claims 5
- 101700022938 CD4 Proteins 0.000 claims 5
- 102100008191 CD8A Human genes 0.000 claims 5
- 101700054655 CD8A Proteins 0.000 claims 5
- 108091006028 chimera Proteins 0.000 claims 5
- 102000005962 receptors Human genes 0.000 claims 4
- 108020003175 receptors Proteins 0.000 claims 4
- 102100007290 CD274 Human genes 0.000 claims 3
- 101710012053 CD274 Proteins 0.000 claims 3
- 102100019283 CD52 Human genes 0.000 claims 3
- 108010065524 CD52 Antigen Proteins 0.000 claims 3
- 102100005175 CSF1R Human genes 0.000 claims 3
- 101700063802 CSF1R Proteins 0.000 claims 3
- 101710004393 HAVCR2 Proteins 0.000 claims 3
- 102100016384 HAVCR2 Human genes 0.000 claims 3
- 102100004550 IL15RA Human genes 0.000 claims 3
- 101710035264 IL15RA Proteins 0.000 claims 3
- 108010065805 Interleukin-12 Proteins 0.000 claims 3
- 108090000172 Interleukin-15 Proteins 0.000 claims 3
- 108010002350 Interleukin-2 Proteins 0.000 claims 3
- 108010002586 Interleukin-7 Proteins 0.000 claims 3
- 102100013504 RPL17 Human genes 0.000 claims 3
- 108060007796 SPATA2 Proteins 0.000 claims 3
- 239000003623 enhancer Substances 0.000 claims 3
- 230000002708 enhancing Effects 0.000 claims 3
- 108010074108 interleukin-21 Proteins 0.000 claims 3
- 108010083359 Antigen Receptors Proteins 0.000 claims 2
- 102000006306 Antigen Receptors Human genes 0.000 claims 2
- 102100019461 CD28 Human genes 0.000 claims 2
- 101700033362 CD28 Proteins 0.000 claims 2
- 102100019453 CD7 Human genes 0.000 claims 2
- 101700063101 CD7 Proteins 0.000 claims 2
- 210000000822 Killer Cells, Natural Anatomy 0.000 claims 2
- 210000000581 Natural Killer T-Cells Anatomy 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
- 238000003776 cleavage reaction Methods 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 201000009251 multiple myeloma Diseases 0.000 claims 2
- 230000002062 proliferating Effects 0.000 claims 2
- 206010002022 Amyloidosis Diseases 0.000 claims 1
- 206010002023 Amyloidosis Diseases 0.000 claims 1
- 206010020631 Hypergammaglobulinaemia benign monoclonal Diseases 0.000 claims 1
- 208000001715 Osteoblastoma Diseases 0.000 claims 1
- 101700059076 PTPRC Proteins 0.000 claims 1
- 102100005499 PTPRC Human genes 0.000 claims 1
- 208000003359 Plasma Cell Leukemia Diseases 0.000 claims 1
- 208000007452 Plasmacytoma Diseases 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 201000008064 heavy chain disease Diseases 0.000 claims 1
- 201000005328 monoclonal gammopathy of uncertain significance Diseases 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
Claims (20)
- 以下を含む操作された細胞
(i.) 第1の抗原認識ドメイン、第1のシグナルペプチド、第1のヒンジ領域、第1の膜貫通ドメイン、第1の共刺激ドメイン、および第1のシグナル伝達ドメインを含む第1のキメラ抗原レセプターポリペプチド、そして
(ii.) 第2の抗原認識ドメイン、第2のシグナルペプチド、第2のヒンジ領域、第2の膜貫通ドメイン、第2の共刺激ドメイン、および第2のシグナル伝達ドメインを含む第2のキメラ抗原受容体ポリペプチドを有する、ここにおいて第1の抗原認識ドメインは第2の抗原認識ドメインとは異なる。 - ここにおける第1のキメラ抗原レセプターポリペプチドおよび第2のキメラエンジニアリングポリペプチドは、単一のポリペプチド分子上にある、そしてまた、ここで、高い効率の切断部位を含むアミノ酸配列は、第1のキメラ抗原レセプターポリペプチドと第2のキメラ抗原レセプターポリペプチドとの間に配置される、請求項1に記載の操作された細胞。
- 高効率切断部位が、P2A、T2A、E2A、およびF2Aからなるグループから選択される請求項2に記載の操作された細胞。
- 第1の共刺激ドメインおよび第2の共刺激ドメインは異なる、請求項1に記載の操作された細胞。
- 第1の共刺激ドメインはCD28を含み、第2の共刺激ドメインは4-1BBを含む、請求項1に記載の操作された細胞。
- 第1の抗原認識ドメインの標的は、インターロイキン6受容体、NY-ESO-1、アルファフェトプロテイン(AFP)、グリピカン-3(GPC3)、BAFF-R、BCMA、TACI、LeY、CD5、CD13、CD14、CD15、CD19、CD20、CD22、CD33、CD41、CD61、CD64、CD68、CD117、CD123、CD138、CD267、CD269、CD38、Flt3受容体そしてCS1からなるグループから選ばれ、第2の抗原認識ドメインの標的はインターロイキン6受容体、NY-ESO-1、アルファフェトプロテイン(AFP)、グリピカン-3(GPC3)、BAFF-R、BCMA、TACI、LeY、CD5、CD13、CD14、CD15、CD19、CD20、CD22、CD33、CD41、CD61、CD64、CD68、CD117、CD123、CD138、CD267、CD269、CD38、Flt3受容体そしてCS1からなるグループより選ばれる、請求項1に記載された操作された細胞。
- 操作された細胞はT細胞、CD4 T細胞、CD8 T細胞、ナチュラルキラー細胞、NKT細胞またはNK-92細胞である、請求項1に記載された操作された細胞。
- CD2、CD3、CD4、CD5、CD7、CD8、CD45、CD52、CD19、CD20、CD22、CD33、CD38、CD123、CD138、CD267、CD269、CD38、およびCS1抗原認識ドメインを含むキメラ抗原レセプターポリペプチドならびに場合によりPD-1、PD-L1、CSF1R、CTAL-4、TIM-3、TGFRベータ、IL-2、IL-7、IL-12、IL-15、IL-15RA、IL-21、それらの機能的フラグメント、またはそれらの組み合わせを含むエンハンサーを含むポリペプチドを含む操作された細胞。
- 機能的断片がsushiドメインを含む、請求項8に記載の操作された細胞。
- 細胞増殖性疾患を治療する方法であって、
a.(i)第1の抗原認識ドメイン、第1のシグナルペプチド、第1のヒンジ領域、第1の膜貫通ドメイン、第1の共刺激ドメイン、および第1のシグナル伝達ドメインを含む第1のキメラ抗原レセプターポリペプチド、ならびに
(ii)第2の抗原認識ドメイン、第2のシグナルペプチド、第2のヒンジ領域、第2の膜貫通ドメイン、第2の共刺激ドメイン、および第2のシグナル伝達ドメインを含む第2のキメラ抗原レセプターポリペプチド
を含む治療上有効量の操作された細胞を、それを必要とする患者に投与する工程であって、
第1の抗原認識ドメインは、第2の抗原認識ドメインとは異なり、
第1のキメラ抗原レセプターポリペプチドは、インターロイキン6受容体、NY-ESO-1、アルファフェトプロテイン(AFP)、グリピカン-3(GPC3)、BAFF-R、BCMA、TACI、LeY、CD5、CD13、CD14、CD15、CD19、CD20、CD22、CD33、CD41、CD61、CD64、CD68、CD117、CD123、CD138、CD267、CD269、CD38、Flt3受容体またはCS1を含み、
第2のキメラ抗原レセプターポリペプチドは、インターロイキン6受容体、NY-ESO-1、アルファフェトプロテイン(AFP)、グリピカン-3(GPC3)、BAFF-R、BCMA、TACI、LeY、CD5、CD13、CD14、CD15、CD19、CD20、CD22、CD33、CD41、CD61、CD64、CD68、CD117、CD123、CD138、CD267、CD269、CD38、Flt3受容体またはCS1を含む工程、あるいは、
CD2、CD3、CD4、CD5、CD7、CD8、CD45、CD52、CD19、CD20、CD22、CD33、CD38、CD123、CD138、CD267、CD269、CD38、およびCS1抗原認識ドメインを含むキメラ抗原レセプターポリペプチドならびに場合によりPD-1、PD-L1、CSF1R、CTAL-4、TIM-3、TGFRベータ、IL-2、IL-7、IL-12、IL-15、IL-15RA、IL-21、それらの機能的フラグメント、またはそれらの組み合わせを含むエンハンサーを含む改変ポリペプチドを含む治療上有効量の操作された細胞を、それを必要とする患者に投与する工程
を含む方法。 - 細胞増殖性疾患が、形質細胞白血病、多発性骨髄腫、形質細胞腫、アミロイドーシス、waldestromのマクログロブリン腫、重鎖疾患、孤立性骨芽細胞腫、不確定性のモノクローナル性ガンマパシー(MGUS)、または多発性骨髄腫のくすぶりを含む、請求項10に記載の方法。
- 細胞が、CD2、CD3、CD4、CD5、CD7、CD8、CD45、CD52、CD19、CD20、CD22、CD33、CD38、CD123、CD138、CD267、CD269、CD38、およびCS1抗原認識ドメインを含むキメラ抗原レセプターポリペプチドならびに場合によりPD-1、PD-L1、CSF1R、CTAL-4、TIM-3、TGFRベータ、IL-2、IL-7、IL-12、IL-15、IL-15RA、IL-21、それらの機能的フラグメント、またはそれらの組み合わせを含むエンハンサーを含む改変ポリペプチドを含まない、請求項10に記載の方法。
- 細胞が、
(i)第1の抗原認識ドメイン、第1のシグナルペプチド、第1のヒンジ領域、第1の膜貫通ドメイン、第1の共刺激ドメイン、および第1のシグナル伝達ドメインを含む第1のキメラ抗原レセプターポリペプチド、ならびに
(ii)第2の抗原認識ドメイン、第2のシグナルペプチド、第2のヒンジ領域、第2の膜貫通ドメイン、第2の共刺激ドメイン、および第2のシグナル伝達ドメインを含む第2のキメラ抗原レセプターポリペプチド
を含まず、
第1の抗原認識ドメインは、第2の抗原認識ドメインとは異なり、
第1のキメラ抗原レセプターポリペプチドは、インターロイキン6受容体、NY-ESO-1、アルファフェトプロテイン(AFP)、グリピカン-3(GPC3)、BAFF-R、BCMA、TACI、LeY、CD5、CD13、CD14、CD15、CD19、CD20、CD22、CD33、CD41、CD61、CD64、CD68、CD117、CD123、CD138、CD267、CD269、CD38、Flt3受容体またはCS1を含み、
第2のキメラ抗原レセプターポリペプチドは、インターロイキン6受容体、NY-ESO-1、アルファフェトプロテイン(AFP)、グリピカン-3(GPC3)、BAFF-R、BCMA、TACI、LeY、CD5、CD13、CD14、CD15、CD19、CD20、CD22、CD33、CD41、CD61、CD64、CD68、CD117、CD123、CD138、CD267、CD269、CD38、Flt3受容体またはCS1を含む、
請求項10に記載の方法。 - 第1の抗原認識ドメインは、CD267またはCD269を含み、第2の抗原認識ドメインは、CD19、CD38、CD138、CD138またはCD1を含む、請求項12に記載の方法。
- 第1の抗原認識ドメインは、CD19を含み、第2の抗原認識ドメインは、CD20、CD22、CD33、CD123、CD267、CD269、CD38またはCD1を含む、請求項12に記載の方法。
- 第1の抗原認識ドメインはCD19を含み、第2の抗原認識ドメインはCD123を含む、請求項12に記載の方法。
- 第1の抗原認識ドメインはCD33を含み、第2の抗原認識ドメインはCD123を含む、請求項12に記載の方法。
- 第1の抗原認識ドメインはBCMAを含み、第2の抗原認識ドメインは、CS1、CD19、CD38、CD138、またはCS1を含む、請求項12に記載の方法。
- 操作された細胞は、T細胞、CD4 T細胞、CD8 T細胞、ナチュラルキラー細胞、NKT細胞またはNK-92細胞である、請求項12に記載の方法。
- 第1の共刺激ドメインはCD28を含み、第2の共刺激ドメインは4-1BBを含む、請求項12に記載の方法。
Priority Applications (2)
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JP2021167360A JP7254870B2 (ja) | 2015-06-25 | 2021-10-12 | キメラ抗体受容体(CARs)の構成およびその使用方法 |
JP2023053851A JP7502515B2 (ja) | 2015-06-25 | 2023-03-29 | キメラ抗体受容体(CARs)の構成およびその使用方法 |
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US201562184321P | 2015-06-25 | 2015-06-25 | |
US62/184,321 | 2015-06-25 | ||
US201562235840P | 2015-10-01 | 2015-10-01 | |
US62/235,840 | 2015-10-01 | ||
US201562244435P | 2015-10-21 | 2015-10-21 | |
US62/244,435 | 2015-10-21 | ||
PCT/US2016/039306 WO2016210293A1 (en) | 2015-06-25 | 2016-06-24 | CHIMERIC ANTIGEN RECEPTORS (CARs), COMPOSITIONS AND METHODS OF USE THEREOF |
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JP2021167360A Active JP7254870B2 (ja) | 2015-06-25 | 2021-10-12 | キメラ抗体受容体(CARs)の構成およびその使用方法 |
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US (1) | US11655452B2 (ja) |
EP (1) | EP3313872A4 (ja) |
JP (3) | JP6961497B2 (ja) |
KR (1) | KR20180021137A (ja) |
CN (2) | CN115058395A (ja) |
AU (3) | AU2016283102B2 (ja) |
CA (1) | CA2990177A1 (ja) |
IL (2) | IL256410B (ja) |
SG (1) | SG10201913682QA (ja) |
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- 2016-06-24 KR KR1020187002389A patent/KR20180021137A/ko not_active Application Discontinuation
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- 2016-06-24 CN CN202210523997.3A patent/CN115058395A/zh active Pending
- 2016-06-24 WO PCT/US2016/039306 patent/WO2016210293A1/en active Application Filing
- 2016-06-24 TW TW105120100A patent/TWI833684B/zh active
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