JP2016507499A5 - - Google Patents
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- JP2016507499A5 JP2016507499A5 JP2015549689A JP2015549689A JP2016507499A5 JP 2016507499 A5 JP2016507499 A5 JP 2016507499A5 JP 2015549689 A JP2015549689 A JP 2015549689A JP 2015549689 A JP2015549689 A JP 2015549689A JP 2016507499 A5 JP2016507499 A5 JP 2016507499A5
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- 229920001184 polypeptide Polymers 0.000 claims 44
- 239000000427 antigen Substances 0.000 claims 20
- 102000038129 antigens Human genes 0.000 claims 20
- 108091007172 antigens Proteins 0.000 claims 20
- 230000000139 costimulatory Effects 0.000 claims 15
- 102100005310 CTLA4 Human genes 0.000 claims 12
- 101700054183 CTLA4 Proteins 0.000 claims 12
- 102100019461 CD28 Human genes 0.000 claims 10
- 101700033362 CD28 Proteins 0.000 claims 10
- 102100019764 PDCD1 Human genes 0.000 claims 8
- 108060007796 SPATA2 Proteins 0.000 claims 8
- 230000003834 intracellular Effects 0.000 claims 8
- 102000004965 antibodies Human genes 0.000 claims 7
- 108090001123 antibodies Proteins 0.000 claims 7
- 102000005632 Single-Chain Antibodies Human genes 0.000 claims 6
- 108010070144 Single-Chain Antibodies Proteins 0.000 claims 6
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 210000001744 T-Lymphocytes Anatomy 0.000 claims 5
- FFILOTSTFMXQJC-QCFYAKGBSA-N (2R,4R,5S,6S)-2-[3-[(2S,3S,4R,6S)-6-[(2S,3R,4R,5S,6R)-5-[(2S,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-[(2R,3S,4R,5R,6R)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(E)-3-hydroxy-2-(octadecanoylamino)octadec-4-enoxy]oxan-3-yl]oxy-3-hy Chemical compound O[C@@H]1[C@@H](O)[C@H](OCC(NC(=O)CCCCCCCCCCCCCCCCC)C(O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@@H]([C@@H](N)[C@H](O)C2)C(O)C(O)CO[C@]2(O[C@@H]([C@@H](N)[C@H](O)C2)C(O)C(O)CO)C(O)=O)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 FFILOTSTFMXQJC-QCFYAKGBSA-N 0.000 claims 2
- 102100003649 ACP3 Human genes 0.000 claims 2
- 102100019459 CD27 Human genes 0.000 claims 2
- 101700056583 CD27 Proteins 0.000 claims 2
- 102100011842 CEACAM5 Human genes 0.000 claims 2
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 claims 2
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims 2
- 101700070897 ENO2 Proteins 0.000 claims 2
- 102100003738 ENO2 Human genes 0.000 claims 2
- 102100008857 MLANA Human genes 0.000 claims 2
- 101710012533 MLANA Proteins 0.000 claims 2
- 102000000440 Melanoma-associated antigen Human genes 0.000 claims 2
- 108050008953 Melanoma-associated antigen Proteins 0.000 claims 2
- 102100017963 PSCA Human genes 0.000 claims 2
- 101700038464 PSCA Proteins 0.000 claims 2
- 101710003940 SPA17 Proteins 0.000 claims 2
- 101710040448 TNFRSF4 Proteins 0.000 claims 2
- 102100013135 TNFRSF4 Human genes 0.000 claims 2
- 230000002159 abnormal effect Effects 0.000 claims 2
- 102000013529 alpha-Fetoproteins Human genes 0.000 claims 2
- 108010026331 alpha-Fetoproteins Proteins 0.000 claims 2
- 210000004027 cells Anatomy 0.000 claims 2
- 108010043671 prostatic acid phosphatase Proteins 0.000 claims 2
- 102100006669 ALPP Human genes 0.000 claims 1
- 102000007469 Actins Human genes 0.000 claims 1
- 108010085238 Actins Proteins 0.000 claims 1
- 101710042656 BQ2027_MB1231C Proteins 0.000 claims 1
- 102100016446 CCDC54 Human genes 0.000 claims 1
- 101710023968 CCDC54 Proteins 0.000 claims 1
- 102100005826 CD19 Human genes 0.000 claims 1
- 101700087100 CD19 Proteins 0.000 claims 1
- 102100000189 CD22 Human genes 0.000 claims 1
- 101700020617 CD22 Proteins 0.000 claims 1
- 108060001251 CD34 Proteins 0.000 claims 1
- 102100016492 CD34 Human genes 0.000 claims 1
- 102100005830 CD70 Human genes 0.000 claims 1
- 101700017377 CD70 Proteins 0.000 claims 1
- 102100016532 CD99 Human genes 0.000 claims 1
- 108060001253 CD99 Proteins 0.000 claims 1
- 102000033243 CDKN2A Human genes 0.000 claims 1
- 101710022338 CDKN2A Proteins 0.000 claims 1
- 102000016843 Calbindin 2 Human genes 0.000 claims 1
- 108010028326 Calbindin 2 Proteins 0.000 claims 1
- 102000010792 Chromogranin A Human genes 0.000 claims 1
- 108010038447 Chromogranin A Proteins 0.000 claims 1
- 102100000789 DES Human genes 0.000 claims 1
- 108010044052 Desmin Proteins 0.000 claims 1
- 102000003425 EC 1.14.18.1 Human genes 0.000 claims 1
- 108060008724 EC 1.14.18.1 Proteins 0.000 claims 1
- 102000013009 EC 2.7.1.40 Human genes 0.000 claims 1
- 108020005115 EC 2.7.1.40 Proteins 0.000 claims 1
- 102100010813 EGF Human genes 0.000 claims 1
- 101700033006 EGF Proteins 0.000 claims 1
- 229940116977 Epidermal Growth Factor Drugs 0.000 claims 1
- 210000004955 Epithelial membranes Anatomy 0.000 claims 1
- 102100012570 GFAP Human genes 0.000 claims 1
- 101700069447 GFAP Proteins 0.000 claims 1
- 102000001389 Glial Fibrillary Acidic Protein Human genes 0.000 claims 1
- 108010093505 Glial Fibrillary Acidic Protein Proteins 0.000 claims 1
- 102100001477 ITGB3 Human genes 0.000 claims 1
- 101710006664 ITGB3 Proteins 0.000 claims 1
- 108010047852 Integrin alphaVbeta3 Proteins 0.000 claims 1
- 102100016985 KIT Human genes 0.000 claims 1
- 101710009391 KIT Proteins 0.000 claims 1
- 101710033922 KRAS Proteins 0.000 claims 1
- 108010076876 Keratins Proteins 0.000 claims 1
- 102000011782 Keratins Human genes 0.000 claims 1
- 102100006037 MUC1 Human genes 0.000 claims 1
- 101700052761 MUC1 Proteins 0.000 claims 1
- 206010025650 Malignant melanoma Diseases 0.000 claims 1
- 108010052285 Membrane Proteins Proteins 0.000 claims 1
- 102000018697 Membrane Proteins Human genes 0.000 claims 1
- 210000003205 Muscles Anatomy 0.000 claims 1
- 102100018287 NKX2-1 Human genes 0.000 claims 1
- 102100016465 PIP Human genes 0.000 claims 1
- 108060006241 PIP Proteins 0.000 claims 1
- 102100006771 PKM Human genes 0.000 claims 1
- 101710039160 PKM Proteins 0.000 claims 1
- 102100005499 PTPRC Human genes 0.000 claims 1
- 101700059076 PTPRC Proteins 0.000 claims 1
- 210000002307 Prostate Anatomy 0.000 claims 1
- 241000713810 Rat sarcoma virus Species 0.000 claims 1
- 108091008153 T cell receptors Proteins 0.000 claims 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims 1
- 102100008336 TG Human genes 0.000 claims 1
- 102100009538 TNFRSF8 Human genes 0.000 claims 1
- 101710040533 TNFRSF8 Proteins 0.000 claims 1
- 102100019730 TP53 Human genes 0.000 claims 1
- 101710026335 TP53 Proteins 0.000 claims 1
- 102100007041 TRPM8 Human genes 0.000 claims 1
- 101700020779 TRPM8 Proteins 0.000 claims 1
- 108010034949 Thyroglobulin Proteins 0.000 claims 1
- 229960002175 Thyroglobulin Drugs 0.000 claims 1
- 108010057966 Thyroid Nuclear Factor 1 Proteins 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 102000003735 mesothelin Human genes 0.000 claims 1
- 108090000015 mesothelin Proteins 0.000 claims 1
- 108010031345 placental alkaline phosphatase Proteins 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 108010014186 ras Proteins Proteins 0.000 claims 1
- 102000016914 ras Proteins Human genes 0.000 claims 1
- -1 synaptophysis Proteins 0.000 claims 1
- 210000004881 tumor cells Anatomy 0.000 claims 1
Claims (17)
- (i) CTLA4又はPD-1由来の膜貫通ドメイン、(ii) CD3ζの細胞内シグナルドメイン、及び(iii) 腫瘍細胞上の抗原に結合する細胞外ドメインを含むポリペプチドであって、
該膜貫通ドメインがCTLA4由来である場合は、該ポリペプチドの細胞外ドメインがCTLA4由来ではなく；かつ
該膜貫通ドメインがPD-1由来である場合は、該ポリペプチドの細胞外ドメインがPD-1由来ではない、前記ポリペプチド。 - キメラ抗原受容体（CAR）である、請求項１記載のポリペプチド。
- 前記ポリペプチドが前記抗原と結合したときに、該ポリペプチドを発現するTリンパ球が、活性化又は刺激され、増殖する、請求項１記載のポリペプチド。
- 前記ポリペプチドが、Tリンパ球表面に発現されたときに、該Tリンパ球に前記抗原を発現する細胞を殺すよう方向づける、請求項１記載のポリペプチド。
- 前記CTLA4の膜貫通ドメインが、ヒトCTLA4遺伝子のエキソン3にコードされるポリペプチド配列である、請求項１記載のポリペプチド。
- 前記細胞外ドメインが、抗体又はその抗原結合部位である、請求項１記載のポリペプチド。
- 前記抗原が、腫瘍関連抗原又は腫瘍特異的抗原である、請求項１記載のポリペプチド。
- 前記腫瘍関連抗原又は腫瘍特異的抗原が、Her2、前立腺幹細胞抗原（PSCA）、アルファ-フェトプロテイン（AFP）、癌胎児性抗原（CEA）、癌抗原-125（CA-125）、CA19-9、カルレチニン、MUC-1、上皮性膜タンパク質（EMA）、上皮性腫瘍抗原（ETA）、チロシナーゼ、メラノーマ関連抗原（MAGE）、CD34、CD45、CD99、CD117、クロモグラニン、サイトケラチン、デスミン、グリア線維酸性タンパク質（GFAP）、肉眼的嚢胞性疾患液体タンパク質（GCDFP-15）、HMB-45抗原、タンパク質メラン-A（Tリンパ球に認識されるメラノーマ抗原；MART-1）、myo-D1、筋特異的アクチン（MSA）、ニューロフィラメント、神経特異的エノラーゼ（NSE）、胎盤アルカリホスファターゼ、シナプトファイシス、チログロブリン、甲状腺転写因子-1、ピルビン酸キナーゼイソ酵素タイプM2の二量体形（腫瘍M2-PK）、CD19、CD22、CD27、CD30、CD70、GD2（ガングリオシドG2）、EGFRvIII（表皮性成長因子バリアントIII）、精子タンパク質17（Sp17）、メソセリン、PAP（前立腺酸性ホスファターゼ）、プロステイン、TARP（T細胞受容体ガンマオルターネイトリーディングフレームタンパク質）、Trp-p8、STEAP1（プロステイト1の6回膜貫通型上皮性抗原）、異常rasタンパク質、異常p53タンパク質、インテグリンαvβ3（CD61）、ガラクチン、K-Ras（V-Ki-ras2キルステンラット肉腫ウイルス癌遺伝子）、又はRal-Bである、請求項７記載のポリペプチド。
- 前記ポリペプチドが、さらに1以上の共刺激性ドメインを含み、該1以上の共刺激性ドメインが、1以上の共刺激性CD27ポリペプチド配列、共刺激性CD28ポリペプチド配列、共刺激性OX40（CD134）ポリペプチド配列、共刺激性4-1BB（CD137）ポリペプチド配列、又は共刺激性誘導性T細胞共刺激性（ICOS）ポリペプチド配列を含む、請求項１記載のポリペプチド。
- 前記ポリペプチドが、N末端からC末端に向けて、順に：(i) 抗原結合ドメイン；(ii) CD28又はCTLA4のヒンジポリペプチド配列；(iii) CTLA4又はPD-1の膜貫通ドメイン；(iv) 共刺激性ドメイン；及び(v) CD3ζの細胞内シグナルドメインを含む、請求項１記載のポリペプチド。
- 前記ポリペプチドが、N末端からC末端に向けて、順に：(i) 可動性リンカーによりVHに連結されるVLを含む、単鎖Fvドメイン、ここで、該VL及びVHは前記抗原に結合する抗体に由来する；(ii) CD28のヒンジポリペプチド配列；(iii) CTLA4の膜貫通ドメイン；(iv) CD28の共刺激性ドメイン；及び(v) CD3ζの細胞内シグナルドメインを含む、請求項１０記載のポリペプチド。
- 前記ポリペプチドが、N末端からC末端に向けて、順に：(i) 可動性リンカーによりVHに連結されるVLを含む、単鎖Fvドメイン、ここで、該VL及びVHは前記抗原に結合する抗体に由来する；(ii) CTLA4のヒンジポリペプチド配列；(iii) CTLA4の膜貫通ドメイン；(iv) CD28の共刺激性ドメイン；及び(v) CD3ζの細胞内シグナルドメインを含む、請求項１０記載のポリペプチド。
- 前記ポリペプチドが、N末端からC末端に向けて、順に：(i) 可動性リンカーによりVHに連結されるVLを含む、単鎖Fvドメイン、ここで、該VL及びVHは前記抗原に結合する抗体に由来する；(ii) CD28のヒンジポリペプチド配列；(iii) PD-1の膜貫通ドメイン；(iv) CD28の共刺激性ドメイン；及び(v) CD3ζの細胞内シグナルドメインを含む、請求項１０記載のポリペプチド。
- 前記ポリペプチドが、N末端からC末端に向けて、順に：(i) 可動性リンカーによりVHに連結されるVLを含む、単鎖Fvドメイン、ここで、該VL及びVHは前記抗原に結合する抗体に由来する；(ii) CTLA4のヒンジポリペプチド配列；(iii) PD-1の膜貫通ドメイン；(iv) CD28の共刺激性ドメイン；及び(v) CD3ζの細胞内シグナルドメインを含む、請求項１０記載のポリペプチド。
- 前記ポリペプチドが、N末端からC末端に向けて、順に：(i) 可動性リンカーによりVHに連結されるVLを含む、単鎖Fvドメイン、ここで、該VL及びVHは前記抗原に結合する抗体に由来する；(ii)PD-1のヒンジポリペプチド配列；(iii) CTLA4の膜貫通ドメイン；(iv) CD28の共刺激性ドメイン；及び(v) CD3ζの細胞内シグナルドメインを含む、請求項１０記載のポリペプチド。
- 前記ポリペプチドが、N末端からC末端に向けて、順に：(i) 可動性リンカーによりVHに連結されるVLを含む、単鎖Fvドメイン、ここで、該VL及びVHは前記抗原に結合する抗体に由来する；(ii)PD-1のヒンジポリペプチド配列；(iii) PD-1の膜貫通ドメイン；(iv) CD28の共刺激性ドメイン；及び(v) CD3ζの細胞内シグナルドメインを含む、請求項１０記載のポリペプチド。
- 請求項１記載のポリペプチドを含むTリンパ球。
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261740113P | 2012-12-20 | 2012-12-20 | |
| US61/740,113 | 2012-12-20 | ||
| US201361779925P | 2013-03-13 | 2013-03-13 | |
| US61/779,925 | 2013-03-13 | ||
| PCT/US2013/076486 WO2014100385A1 (en) | 2012-12-20 | 2013-12-19 | Chimeric antigen receptors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018100931A Division JP6697026B2 (ja) | 2012-12-20 | 2018-05-25 | キメラ抗原受容体 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016507499A JP2016507499A (ja) | 2016-03-10 |
| JP2016507499A5 true JP2016507499A5 (ja) | 2017-02-09 |
| JP6422883B2 JP6422883B2 (ja) | 2018-11-21 |
Family
ID=50979209
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015549689A Active JP6422883B2 (ja) | 2012-12-20 | 2013-12-19 | キメラ抗原受容体 |
| JP2018100931A Active JP6697026B2 (ja) | 2012-12-20 | 2018-05-25 | キメラ抗原受容体 |
| JP2020076729A Active JP6992117B2 (ja) | 2012-12-20 | 2020-04-23 | キメラ抗原受容体 |
| JP2021199109A Pending JP2022033930A (ja) | 2012-12-20 | 2021-12-08 | キメラ抗原受容体 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018100931A Active JP6697026B2 (ja) | 2012-12-20 | 2018-05-25 | キメラ抗原受容体 |
| JP2020076729A Active JP6992117B2 (ja) | 2012-12-20 | 2020-04-23 | キメラ抗原受容体 |
| JP2021199109A Pending JP2022033930A (ja) | 2012-12-20 | 2021-12-08 | キメラ抗原受容体 |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US10150816B2 (ja) |
| EP (3) | EP2935321B1 (ja) |
| JP (4) | JP6422883B2 (ja) |
| KR (2) | KR102254978B1 (ja) |
| CN (2) | CN105246912B (ja) |
| AU (1) | AU2013204922B2 (ja) |
| CA (2) | CA2895840C (ja) |
| ES (2) | ES2864507T3 (ja) |
| HK (1) | HK1215267A1 (ja) |
| IL (1) | IL239500B (ja) |
| SG (2) | SG11201504855WA (ja) |
| WO (1) | WO2014100385A1 (ja) |
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| CN105358576B (zh) | 2013-02-20 | 2020-05-05 | 诺华股份有限公司 | 使用人源化抗EGFRvIII嵌合抗原受体治疗癌症 |
| EP4098275A1 (en) * | 2013-03-15 | 2022-12-07 | Memorial Sloan-Kettering Cancer Center | Compositions and methods for immunotherapy |
| US9745368B2 (en) * | 2013-03-15 | 2017-08-29 | The Trustees Of The University Of Pennsylvania | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
| EP2970372B1 (en) | 2013-03-15 | 2020-09-30 | Celgene Corporation | Modified t lymphocytes |
| KR102095700B1 (ko) | 2013-05-14 | 2020-04-01 | 보드 오브 리전츠, 더 유니버시티 오브 텍사스 시스템 | 가공된 키메라 항원 수용체 (ｃａｒ) ｔ-세포의 인간 적용 |
| CA2913052A1 (en) | 2013-05-24 | 2014-11-27 | Board Of Regents, The University Of Texas System | Chimeric antigen receptor-targeting monoclonal antibodies |
| NZ725169A (en) | 2014-04-25 | 2018-02-23 | Bluebird Bio Inc | Mnd promoter chimeric antigen receptors |
| ES2791953T3 (es) * | 2014-06-06 | 2020-11-06 | Us Health | Receptores de antígeno quimérico dirigidos a mesotelina y usos de los mismos |
| CA2951044C (en) | 2014-06-06 | 2023-10-03 | Bluebird Bio, Inc. | Improved t cell compositions |
| CN107075483A (zh) * | 2014-07-15 | 2017-08-18 | 朱诺治疗学股份有限公司 | 用于过继细胞治疗的工程改造的细胞 |
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| US20170226216A1 (en) * | 2014-07-24 | 2017-08-10 | Bluebird Bio, Inc. | Bcma chimeric antigen receptors |
| WO2016026143A1 (en) | 2014-08-22 | 2016-02-25 | Huiru Wang | Saccharide-based biomarkers and therapeutics |
| ES2777305T3 (es) * | 2014-09-04 | 2020-08-04 | Cellectis | Receptores de antígeno quiméricos específicos de la glicoproteína trofoblástica (5T4, TPBG) para inmunoterapia contra el cáncer |
| JP6684782B2 (ja) | 2014-09-15 | 2020-04-22 | モルメド エスピーエー | キメラ抗原受容体 |
| CA2964785A1 (en) * | 2014-11-05 | 2016-05-12 | Board Of Regents, The University Of Texas System | Gene modified immune effector cells and engineered cells for expansion of immune effector cells |
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