JP2018531612A5 - - Google Patents
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- JP2018531612A5 JP2018531612A5 JP2018521598A JP2018521598A JP2018531612A5 JP 2018531612 A5 JP2018531612 A5 JP 2018531612A5 JP 2018521598 A JP2018521598 A JP 2018521598A JP 2018521598 A JP2018521598 A JP 2018521598A JP 2018531612 A5 JP2018531612 A5 JP 2018531612A5
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- 210000004027 cells Anatomy 0.000 claims 47
- 229920000023 polynucleotide Polymers 0.000 claims 15
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims 12
- 239000002157 polynucleotide Substances 0.000 claims 11
- 108091008153 T cell receptors Proteins 0.000 claims 10
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims 10
- 102100015541 FCGR3A Human genes 0.000 claims 8
- 101710044656 FCGR3A Proteins 0.000 claims 8
- 101710044657 FCGR3B Proteins 0.000 claims 8
- 210000004263 Induced Pluripotent Stem Cells Anatomy 0.000 claims 7
- 238000010362 genome editing Methods 0.000 claims 6
- 210000001744 T-Lymphocytes Anatomy 0.000 claims 5
- 230000003394 haemopoietic Effects 0.000 claims 5
- 102100003404 HLA-G Human genes 0.000 claims 3
- 108010024164 HLA-G Antigens Proteins 0.000 claims 3
- 108020003175 receptors Proteins 0.000 claims 3
- 102000005962 receptors Human genes 0.000 claims 3
- 101710026059 ABCB27 Proteins 0.000 claims 2
- 101700064281 ATP1 Proteins 0.000 claims 2
- 101710025939 At5g53970 Proteins 0.000 claims 2
- 102100007290 CD274 Human genes 0.000 claims 2
- 101710012053 CD274 Proteins 0.000 claims 2
- 102100013078 CD47 Human genes 0.000 claims 2
- 101700033237 CD47 Proteins 0.000 claims 2
- 102100019451 CD80 Human genes 0.000 claims 2
- 101700080477 CD80 Proteins 0.000 claims 2
- 102100015521 CIITA Human genes 0.000 claims 2
- 101710042948 CIITA Proteins 0.000 claims 2
- 210000000349 Chromosomes Anatomy 0.000 claims 2
- 108010087819 Fc receptors Proteins 0.000 claims 2
- 102000009109 Fc receptors Human genes 0.000 claims 2
- 101710004393 HAVCR2 Proteins 0.000 claims 2
- 102100016384 HAVCR2 Human genes 0.000 claims 2
- 102100003408 HLA-E Human genes 0.000 claims 2
- 101710009009 HLA-E Proteins 0.000 claims 2
- 210000000822 Killer Cells, Natural Anatomy 0.000 claims 2
- 108060004270 LAG3 Proteins 0.000 claims 2
- 102100017213 LAG3 Human genes 0.000 claims 2
- 108010023335 Member 2 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 claims 2
- 102100017337 NLRC5 Human genes 0.000 claims 2
- 101700003408 NLRC5 Proteins 0.000 claims 2
- 101700070190 PER2 Proteins 0.000 claims 2
- 210000000173 Precursor Cells, T-Lymphoid Anatomy 0.000 claims 2
- 102100005317 RFX5 Human genes 0.000 claims 2
- 101700020218 RFX5 Proteins 0.000 claims 2
- 102100006028 RFXANK Human genes 0.000 claims 2
- 101710004703 RFXANK Proteins 0.000 claims 2
- 102100006029 RFXAP Human genes 0.000 claims 2
- 101700029140 RFXAP Proteins 0.000 claims 2
- 101710026776 SEC14L3 Proteins 0.000 claims 2
- 102100018522 SNCA Human genes 0.000 claims 2
- 108060007796 SPATA2 Proteins 0.000 claims 2
- 102100017432 TAP1 Human genes 0.000 claims 2
- 102100017433 TAP2 Human genes 0.000 claims 2
- 101700031988 TAP2 Proteins 0.000 claims 2
- 102100001185 TAPBP Human genes 0.000 claims 2
- 210000003411 Telomere Anatomy 0.000 claims 2
- 239000000427 antigen Substances 0.000 claims 2
- 102000038129 antigens Human genes 0.000 claims 2
- 108091007172 antigens Proteins 0.000 claims 2
- 238000002659 cell therapy Methods 0.000 claims 2
- 108091006028 chimera Proteins 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 210000001778 pluripotent stem cell Anatomy 0.000 claims 2
- 210000000130 stem cell Anatomy 0.000 claims 2
- 108010059434 tapasin Proteins 0.000 claims 2
- 229920000511 telomere Polymers 0.000 claims 2
- -1 41BBL Proteins 0.000 claims 1
- 206010003816 Autoimmune disease Diseases 0.000 claims 1
- 210000003719 B-Lymphocytes Anatomy 0.000 claims 1
- 102100011514 B2M Human genes 0.000 claims 1
- 101710003640 B2M Proteins 0.000 claims 1
- 102100005826 CD19 Human genes 0.000 claims 1
- 101700087100 CD19 Proteins 0.000 claims 1
- 210000002889 Endothelial Cells Anatomy 0.000 claims 1
- 241000829111 Human polyomavirus 1 Species 0.000 claims 1
- 210000004693 NK cell Anatomy 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 241000724205 Rice stripe tenuivirus Species 0.000 claims 1
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000003247 decreasing Effects 0.000 claims 1
- 230000004069 differentiation Effects 0.000 claims 1
- 201000009910 diseases by infectious agent Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 201000005787 hematologic cancer Diseases 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 230000002688 persistence Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 230000035755 proliferation Effects 0.000 claims 1
- 230000033300 receptor internalization Effects 0.000 claims 1
- 230000004083 survival Effects 0.000 claims 1
- 241000701161 unidentified adenovirus Species 0.000 claims 1
Claims (22)
- (i)細胞が人工多能性幹細胞(iPSC)、クローンiPSC、iPSC系統細胞、又は前記iPSCから分化したiPSC由来細胞であり;及び(ii)細胞は、内因性T細胞受容体(TCR)α遺伝子座に1つ以上の外因性ポリヌクレオチドを含み、1つ以上の外因性ポリヌクレオチドの少なくとも1つはキメラ抗原受容体(CAR)をコードし、及び1つ以上のCARをコードする外因性ポリヌクレオチドは、前記TCRα遺伝子座の内因性プロモーターの制御下で発現される、細胞又はその集団。
- 1つ以上の外因性ポリヌクレオチドが、TCRα遺伝子座の定常領域をコードする核酸中に存在する、請求項1に記載の細胞又はその集団。
- 内因性TCRα遺伝子がノックアウトされている、請求項2に記載の細胞又はその集団。
- CARが、内因性TCRα遺伝子がノックアウトされていない参照細胞において内因性TCRα遺伝子とほぼ同じレベルで発現される、請求項3記載の細胞又はその集団。
- 前記CARが、内因性TCRα遺伝子がノックアウトされていない参照細胞において、内因性TCRαとほぼ同じ発達段階で発現される、請求項3記載の細胞又はその集団。
- 前記少なくとも1つのCARがCD19関連CARを含む、請求項1に記載の細胞又はその集団。
- CD16が導入された又は増加した発現を更に含み、前記CD16が高親和性の切断不可能なCD16(hnCD16)である、請求項1〜6のいずれか1項に記載の細胞又はその集団。
- CD3の発現の導入又は増加を更に含む、請求項1〜7のいずれか1項に記載の細胞又はその集団。
- B2M及びCIITAの少なくとも一方の欠失又は発現低下、及び任意でHLA-Gの発現の導入又は増加を更に含む、請求項1〜8のいずれか1項に記載の細胞又はその集団。
- 前記細胞が、T細胞を多能性状態(TiPSC)に再プログラミングし、TiPSCをゲノム編集することから得られるiPSCである、請求項1に記載の細胞又はその集団。
- 前記細胞が、TCRα遺伝子座の定常領域をコードする核酸中に存在する1つ又は複数の外因性ポリヌクレオチドを含むT細胞を再プログラミングすることから得られるiPSCである、請求項10記載の細胞又はその集団。
- TAP1、TAP2、タパシン、NLRC5、PD1、LAG3、TIM3、RFXANK、RFX5、RFXAP、及び染色体6p21領域の少なくとも1つにおいて、欠失又は発現低下;及び/又は、HLA-E、HLA-G、CD16、41BBL、CD4、CD8、CD47、CD113、CD131、CD137、CD80、PDL1、A2AR、Fc受容体、エンゲージャー、及び二重、多重特異性又は汎用エンゲージャーと結合するための表面トリガー受容体内の任意の遺伝子の少なくとも1つにおいて、発現の導入又は増加を更に含む、請求項1〜11のいずれか1項に記載の細胞又はその集団。
- 前記細胞が前記iPSCから分化したiPSC由来細胞であり、前記細胞がiPSC由来造血系細胞である、請求項1〜12のいずれか1項に記載の細胞又はその集団。
- iPSC由来の造血系細胞が、最終的な造血内皮細胞、T細胞前駆細胞、T細胞、NK細胞前駆細胞、NK細胞、又はB細胞; 及びiPSCから分化した前記造血系細胞は、iPSCに由来しない同じ種類の細胞よりも長いテロメア長を含む、請求項1〜13のいずれか1項に記載の細胞又はその集団。
- iPSC由来の造血系細胞がT細胞、T細胞前駆体、又はそのクローン細胞であり、及び前記iPSC由来のT細胞又はT細胞前駆体が以下の少なくとも1つの特徴:
(i)細胞療法においてHLAマッチングを必要としない;
(ii)iPSCに由来しない同じ種類の細胞よりも長いテロメア長を含む; 及び
(iii)iPSCから派生していない同じ種類の細胞と比較して、より大きな増殖、生存、及び/又は持続性の可能性を示す、
を持つ、請求項1〜14のいずれか1項に記載の細胞又はその集団。 - 細胞又はその集団を生成する方法であって、(i)前記細胞が人工多能性幹細胞(iPSC)、クローンiPSC、iPSC系統細胞、又はiPSCから分化したiPSC由来細胞である;(ii)前記細胞は、内因性T細胞受容体(TCR)α遺伝子座に1つ以上の外因性ポリヌクレオチドを含み、前記1つ以上の外因性ポリヌクレオチドの少なくとも1つはキメラ抗原受容体(CAR)をコードし、及び1つ以上のCARをコードする外因性ポリヌクレオチドは、前記TCRα遺伝子座の内因性プロモーターの制御下で発現され、(iii)前記方法は(I)又は(II)の段階を含む:
(I):
(i)T細胞を人工多能性幹細胞(iPSC)に再プログラミングする;及び
(ii)iPSCをゲノム編集して、同時又は順次に、
(a)TCRα遺伝子座の定常領域をコードするポリ核酸を破壊することにより、T細胞受容体(TCR)をノックアウトする;及び
(b)TCRαの定常領域をコードするポリ核酸において少なくとも1つのキメラ抗原受容体(CAR)をコードするポリヌクレオチドをノックインする; 少なくとも1つのCARをコードするポリヌクレオチドは、TCRα遺伝子座の内因性TCRプロモーターの制御下で発現する;
それによって、ゲノム編集されたiPSCを取得する;
又は、(II):
(i)T細胞をゲノム編集し、同時又は順次に、
(a)TCRα遺伝子座の定常領域をコードするポリ核酸を破壊することにより、T細胞受容体(TCR)をノックアウトする;及び
(b)TCRαの定常領域をコードするポリ核酸で少なくとも1つのキメラ抗原受容体(CAR)をコードするポリヌクレオチドをノックインする; 少なくとも1つのCARをコードするポリヌクレオチドは、TCRα遺伝子座の内因性TCRプロモーターの制御下で発現する;
それによって、ゲノム編集されたT細胞が得られる;及び
(ii)段階(II)(i)のゲノム編集されたT細胞を誘導多能性幹細胞(iPSC)に再プログラミングする、ここでiPSCは段階(II)(i)のT細胞と同じゲノム編集を含む、細胞又はその集団を生成する方法。 - (I)又は(II)の段階(ii)のゲノム編集されたiPSCの分化を指示し、iPSC由来細胞又はその集団を得る段階を更に含む、請求項16に記載の方法。
- (I)(ii)又は(II)(i)のゲノム編集が、B2M、TAP1、TAP2、タパシン、NLRC5、PD1、LAG3、TIM3、RFXANK、CIITA、RFX5、RFXAP、及び染色体6p21領域の任意の遺伝子の少なくとも1つの発現を欠失又は減少させること;並びに/又はHLA-E、HLA-G、CD16、41BBL、CD3、CD4、CD8、CD47、CD113、CD131、CD137、CD80、PDL1、A2AR、Fc受容体、エンゲージャー、二重、多重特異的若しくは普遍的エンゲージャーと結合するための表面トリガー受容体、の少なくとも1つにおける発現の導入又は増加をさらに含む、請求項16又は17に記載の方法。
- (I)(ii)又は(II)(i)のゲノム編集が、CD16の発現を導入又は増加を更に含み、前記CD16が高親和性の切断不可能なCD16(hnCD16)である、請求項16〜18のいずれか一項に記載の方法。
- 前記(I)(ii)又は(II)(i)のゲノム編集が、CD3の発現を導入又は増加させることを更に含む、請求項16〜19のいずれか一項に記載の方法。
- 薬剤的に許容できる培地及び、請求項1〜15のいずれか一項に記載の細胞又はその集団とを含む医薬組成物。
- 自己免疫障害;造血器腫瘍; 固形腫瘍; がん、又はHIV、RSV、EBV、CMV、アデノウイルス、又はBKポリオーマウイルスと関連した感染症の治療に使用するための請求項21に記載の医薬組成物であって、前記使用は、養子細胞療法を必要とする対象に組成物を導入することを含む、医薬組成物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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JP2021130046A JP2021191272A (ja) | 2015-11-04 | 2021-08-06 | 万能性細胞のゲノム改変 |
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
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US201562251032P | 2015-11-04 | 2015-11-04 | |
US62/251,032 | 2015-11-04 | ||
US201662337258P | 2016-05-16 | 2016-05-16 | |
US62/337,258 | 2016-05-16 | ||
US201662366503P | 2016-07-25 | 2016-07-25 | |
US62/366,503 | 2016-07-25 | ||
PCT/US2016/060699 WO2017079673A1 (en) | 2015-11-04 | 2016-11-04 | Genomic engineering of pluripotent cells |
Related Child Applications (1)
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JP2021130046A Division JP2021191272A (ja) | 2015-11-04 | 2021-08-06 | 万能性細胞のゲノム改変 |
Publications (3)
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JP2018531612A JP2018531612A (ja) | 2018-11-01 |
JP2018531612A5 true JP2018531612A5 (ja) | 2019-12-12 |
JP6928604B2 JP6928604B2 (ja) | 2021-09-01 |
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JP2018521598A Active JP6928604B2 (ja) | 2015-11-04 | 2016-11-04 | 万能性細胞のゲノム改変 |
JP2021130046A Pending JP2021191272A (ja) | 2015-11-04 | 2021-08-06 | 万能性細胞のゲノム改変 |
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JP2021130046A Pending JP2021191272A (ja) | 2015-11-04 | 2021-08-06 | 万能性細胞のゲノム改変 |
Country Status (12)
Country | Link |
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US (4) | US10287606B2 (ja) |
EP (2) | EP3371314B1 (ja) |
JP (2) | JP6928604B2 (ja) |
KR (1) | KR20180066262A (ja) |
CN (2) | CN115806940A (ja) |
AU (2) | AU2016349504B2 (ja) |
CA (1) | CA3003150A1 (ja) |
ES (1) | ES2953925T3 (ja) |
HK (1) | HK1258739A1 (ja) |
PT (1) | PT3371314T (ja) |
SG (1) | SG11201803144WA (ja) |
WO (1) | WO2017079673A1 (ja) |
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