JP2019536469A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2019536469A5 JP2019536469A5 JP2019537030A JP2019537030A JP2019536469A5 JP 2019536469 A5 JP2019536469 A5 JP 2019536469A5 JP 2019537030 A JP2019537030 A JP 2019537030A JP 2019537030 A JP2019537030 A JP 2019537030A JP 2019536469 A5 JP2019536469 A5 JP 2019536469A5
- Authority
- JP
- Japan
- Prior art keywords
- nucleic acid
- seq
- cells
- pharmaceutical composition
- acid sequence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000007523 nucleic acids Chemical group 0.000 claims description 62
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 35
- 108020004707 nucleic acids Proteins 0.000 claims description 32
- 102000039446 nucleic acids Human genes 0.000 claims description 32
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 29
- 201000011510 cancer Diseases 0.000 claims description 28
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 23
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 claims description 22
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 claims description 22
- 201000006966 adult T-cell leukemia Diseases 0.000 claims description 22
- 150000001413 amino acids Chemical class 0.000 claims description 21
- 230000011664 signaling Effects 0.000 claims description 16
- 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 group 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 description 12
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 claims description 12
- 102100032976 CCR4-NOT transcription complex subunit 6 Human genes 0.000 claims description 12
- 239000013598 vector Substances 0.000 claims description 12
- 210000004027 cell Anatomy 0.000 claims description 10
- 108020004999 messenger RNA Proteins 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 210000000822 natural killer cell Anatomy 0.000 claims description 9
- 208000000389 T-cell leukemia Diseases 0.000 claims description 8
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 claims description 8
- 230000004853 protein function Effects 0.000 claims description 8
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 7
- 239000013604 expression vector Substances 0.000 claims description 7
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 claims description 6
- 208000017604 Hodgkin disease Diseases 0.000 claims description 6
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 6
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 6
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 6
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 claims description 6
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 6
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 claims description 6
- 230000001684 chronic effect Effects 0.000 claims description 6
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 claims description 6
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 6
- 230000003834 intracellular effect Effects 0.000 claims description 6
- 201000005962 mycosis fungoides Diseases 0.000 claims description 6
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 6
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 4
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 4
- 108060003951 Immunoglobulin Proteins 0.000 claims description 4
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 201000004101 esophageal cancer Diseases 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 102000018358 immunoglobulin Human genes 0.000 claims description 4
- 210000004080 milk Anatomy 0.000 claims description 4
- 239000008267 milk Substances 0.000 claims description 4
- 235000013336 milk Nutrition 0.000 claims description 4
- 210000001672 ovary Anatomy 0.000 claims description 4
- 210000002784 stomach Anatomy 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- 241001663880 Gammaretrovirus Species 0.000 claims description 2
- 241000713666 Lentivirus Species 0.000 claims description 2
- 241000700605 Viruses Species 0.000 claims description 2
- 210000004899 c-terminal region Anatomy 0.000 claims description 2
- 210000005260 human cell Anatomy 0.000 claims description 2
- 230000001926 lymphatic effect Effects 0.000 claims description 2
- 210000003289 regulatory T cell Anatomy 0.000 claims description 2
- 239000013603 viral vector Substances 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 10
- 239000003814 drug Substances 0.000 claims 1
- 230000002463 transducing effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662397810P | 2016-09-21 | 2016-09-21 | |
| US62/397,810 | 2016-09-21 | ||
| PCT/US2017/052437 WO2018057585A1 (en) | 2016-09-21 | 2017-09-20 | Chimeric antigen receptor (car) that targets chemokine receptor ccr4 and its use |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021003261A Division JP2021052804A (ja) | 2016-09-21 | 2021-01-13 | ケモカイン受容体ｃｃｒ４を標的にするキメラ抗原受容体（ｃａｒ）およびその使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019536469A JP2019536469A (ja) | 2019-12-19 |
| JP2019536469A5 true JP2019536469A5 (enExample) | 2020-11-05 |
| JP6908710B2 JP6908710B2 (ja) | 2021-07-28 |
Family
ID=60002059
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019537030A Active JP6908710B2 (ja) | 2016-09-21 | 2017-09-20 | ケモカイン受容体ｃｃｒ４を標的にするキメラ抗原受容体（ｃａｒ）およびその使用 |
| JP2021003261A Withdrawn JP2021052804A (ja) | 2016-09-21 | 2021-01-13 | ケモカイン受容体ｃｃｒ４を標的にするキメラ抗原受容体（ｃａｒ）およびその使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021003261A Withdrawn JP2021052804A (ja) | 2016-09-21 | 2021-01-13 | ケモカイン受容体ｃｃｒ４を標的にするキメラ抗原受容体（ｃａｒ）およびその使用 |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US11077178B2 (enExample) |
| EP (1) | EP3515475B1 (enExample) |
| JP (2) | JP6908710B2 (enExample) |
| AU (1) | AU2017332161B9 (enExample) |
| CA (1) | CA3037518A1 (enExample) |
| WO (1) | WO2018057585A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018057585A1 (en) | 2016-09-21 | 2018-03-29 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric antigen receptor (car) that targets chemokine receptor ccr4 and its use |
| EP4549555A3 (en) * | 2019-05-24 | 2025-07-30 | City of Hope | Ccr4 targeted chimeric antigen receptor modified t cells for treatment of ccr4 positive malignancies |
| WO2021105989A1 (en) * | 2019-11-26 | 2021-06-03 | Ramot At Tel-Aviv University Ltd. | Chimeric antigen receptor to carbohydrate antigens |
| WO2022173950A1 (en) * | 2021-02-11 | 2022-08-18 | The Trustees Of The University Of Pennsylvania | Ccr4-targeting chimeric antigen receptor cell therapy |
| WO2022211046A1 (ja) * | 2021-03-31 | 2022-10-06 | 塩野義製薬株式会社 | Ｃｃｒ８を抗原として認識するキメラ抗原受容体 |
| KR20240007204A (ko) * | 2021-05-11 | 2024-01-16 | 싱가포르 헬스 서비시즈 피티이 엘티디 | 키메라 항원 수용체 및 이를 포함하는 변형된 세포 |
| WO2024248490A1 (ko) * | 2023-05-30 | 2024-12-05 | 아주대학교산학협력단 | Pd-l1을 표적으로 하는 키메라 항원 수용체 및 이를 발현하는 t 세포 치료제 |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR901228A (fr) | 1943-01-16 | 1945-07-20 | Deutsche Edelstahlwerke Ag | Système d'aimant à entrefer annulaire |
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US4722848A (en) | 1982-12-08 | 1988-02-02 | Health Research, Incorporated | Method for immunizing animals with synthetically modified vaccinia virus |
| GB2116183B (en) | 1982-03-03 | 1985-06-05 | Genentech Inc | Human antithrombin iii dna sequences therefore expression vehicles and cloning vectors containing such sequences and cell cultures transformed thereby a process for expressing human antithrombin iii and pharmaceutical compositions comprising it |
| US5858358A (en) | 1992-04-07 | 1999-01-12 | The United States Of America As Represented By The Secretary Of The Navy | Methods for selectively stimulating proliferation of T cells |
| US6352694B1 (en) | 1994-06-03 | 2002-03-05 | Genetics Institute, Inc. | Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells |
| US6905680B2 (en) | 1988-11-23 | 2005-06-14 | Genetics Institute, Inc. | Methods of treating HIV infected subjects |
| US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
| US5643578A (en) | 1992-03-23 | 1997-07-01 | University Of Massachusetts Medical Center | Immunization by inoculation of DNA transcription unit |
| EP0671926B1 (en) | 1992-08-11 | 2002-11-13 | President And Fellows Of Harvard College | Immunomodulatory peptides |
| US5593972A (en) | 1993-01-26 | 1997-01-14 | The Wistar Institute | Genetic immunization |
| US7175843B2 (en) | 1994-06-03 | 2007-02-13 | Genetics Institute, Llc | Methods for selectively stimulating proliferation of T cells |
| US6692964B1 (en) | 1995-05-04 | 2004-02-17 | The United States Of America As Represented By The Secretary Of The Navy | Methods for transfecting T cells |
| US7067318B2 (en) | 1995-06-07 | 2006-06-27 | The Regents Of The University Of Michigan | Methods for transfecting T cells |
| DK0920505T3 (da) | 1996-08-16 | 2008-09-08 | Schering Corp | Pattedyrcelleoverfladeantigener og tilhörende reagenser |
| US6111090A (en) | 1996-08-16 | 2000-08-29 | Schering Corporation | Mammalian cell surface antigens; related reagents |
| CA2308114A1 (en) | 1997-10-21 | 1999-04-29 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor-like proteins tr11, tr11sv1, and tr11sv2 |
| JP2002502607A (ja) | 1998-02-09 | 2002-01-29 | ジェネンテク・インコーポレイテッド | 新規な腫瘍壊死因子レセプター相同体及びそれをコードする核酸 |
| ATE376837T1 (de) | 1999-07-12 | 2007-11-15 | Genentech Inc | Stimulierung oder hemmung von angiogenese und herzvaskularisierung mit tumor nekrose faktor ligand/rezeptor homologen |
| US6797514B2 (en) | 2000-02-24 | 2004-09-28 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
| HK1052372A1 (zh) | 2000-02-24 | 2003-09-11 | Xcyte Therapies, Inc. | 细胞的同步刺激和富集 |
| US6867041B2 (en) | 2000-02-24 | 2005-03-15 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
| US7572631B2 (en) | 2000-02-24 | 2009-08-11 | Invitrogen Corporation | Activation and expansion of T cells |
| EP1478648B1 (en) | 2002-02-01 | 2014-04-30 | ARIAD Pharmaceuticals, Inc. | Phosphorus-containing compounds and uses thereof |
| US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
| ES2367430T3 (es) | 2002-12-23 | 2011-11-03 | Wyeth Llc | Anticuerpos contra pd-1 y sus usos. |
| AU2004244626A1 (en) | 2003-05-23 | 2004-12-09 | The Government Of The United States Of America As Represented By The Secretary, Department Of Health And Human Services | GITR ligand and GITR ligand-related molecules and antibodies and uses thereof |
| EP1660126A1 (en) | 2003-07-11 | 2006-05-31 | Schering Corporation | Agonists or antagonists of the clucocorticoid-induced tumour necrosis factor receptor (gitr) or its ligand for the treatment of immune disorders, infections and cancer |
| EP1692318A4 (en) | 2003-12-02 | 2008-04-02 | Genzyme Corp | COMPOSITIONS AND METHODS FOR DIAGNOSIS AND TREATMENT OF LUNG CANCER |
| GB0409799D0 (en) | 2004-04-30 | 2004-06-09 | Isis Innovation | Method of generating improved immune response |
| EP1765402A2 (en) | 2004-06-04 | 2007-03-28 | Duke University | Methods and compositions for enhancement of immunity by in vivo depletion of immunosuppressive cell activity |
| JP5238936B2 (ja) | 2005-03-25 | 2013-07-17 | ジーアイティーアール，インク． | Ｇｉｔｒ結合分子およびその使用 |
| EP3530736A3 (en) | 2005-05-09 | 2019-11-06 | ONO Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1 (pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics |
| KR101704734B1 (ko) | 2005-07-01 | 2017-02-09 | 이. 알. 스퀴부 앤드 선즈, 엘.엘.씨. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날 항체 |
| WO2007133822A1 (en) | 2006-01-19 | 2007-11-22 | Genzyme Corporation | Gitr antibodies for the treatment of cancer |
| US20090258005A1 (en) * | 2007-05-29 | 2009-10-15 | Trubion Pharmaceuticals Inc. | Therapeutic compositions and methods |
| PT2170959E (pt) | 2007-06-18 | 2014-01-07 | Merck Sharp & Dohme | Anticorpos para o receptor humano de morte programada pd-1 |
| PT2175884T (pt) | 2007-07-12 | 2016-09-21 | Gitr Inc | Terapias de combinação empregando moléculas de ligação a gitr |
| PT2242773T (pt) | 2008-02-11 | 2017-09-15 | Cure Tech Ltd | Anticorpos monoclonais para o tratamento de tumores |
| US8168757B2 (en) | 2008-03-12 | 2012-05-01 | Merck Sharp & Dohme Corp. | PD-1 binding proteins |
| JP2011526794A (ja) | 2008-07-02 | 2011-10-20 | エマージェント プロダクト デベロップメント シアトル， エルエルシー | ＴＧＦ−βアンタゴニスト多重標的結合性分子 |
| EA201500417A1 (ru) | 2008-08-25 | 2015-11-30 | Эмплиммьюн, Инк. | Композиции антагонистов pd-1 и способы применения |
| WO2010098788A2 (en) | 2008-08-25 | 2010-09-02 | Amplimmune, Inc. | Pd-i antagonists and methods for treating infectious disease |
| JPWO2010030002A1 (ja) | 2008-09-12 | 2012-02-02 | 国立大学法人三重大学 | 外来性ｇｉｔｒリガンド発現細胞 |
| MX356367B (es) | 2008-12-09 | 2018-05-25 | Genentech Inc | Anticuerpos anti-pd-l1 y su uso para mejorar la funcion de celulas t. |
| WO2010089411A2 (en) | 2009-02-09 | 2010-08-12 | Universite De La Mediterranee | Pd-1 antibodies and pd-l1 antibodies and uses thereof |
| IN2015DN02826A (enExample) | 2009-09-03 | 2015-09-11 | Merck Sharp & Dohme | |
| JP5934099B2 (ja) | 2009-10-01 | 2016-06-15 | アメリカ合衆国 | 抗血管内皮増殖因子受容体−２キメラ抗原受容体及び癌の治療のためのその使用 |
| GB0919054D0 (en) | 2009-10-30 | 2009-12-16 | Isis Innovation | Treatment of obesity |
| EP2504028A4 (en) | 2009-11-24 | 2014-04-09 | Amplimmune Inc | SIMULTANEOUS INHIBITION OF PD-L1 / PD-L2 |
| US20130089554A1 (en) | 2009-12-29 | 2013-04-11 | Emergent Product Development Seattle, Llc | RON Binding Constructs and Methods of Use Thereof |
| PH12013501201A1 (en) * | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| JP2014509841A (ja) | 2011-01-18 | 2014-04-24 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | 癌を治療するための組成物および方法 |
| US20130108641A1 (en) | 2011-09-14 | 2013-05-02 | Sanofi | Anti-gitr antibodies |
| JP6267644B2 (ja) | 2011-10-20 | 2018-01-24 | アメリカ合衆国 | 抗ｃｄ２２キメラ抗原受容体 |
| EP2814846B1 (en) * | 2012-02-13 | 2020-01-08 | Seattle Children's Hospital d/b/a Seattle Children's Research Institute | Bispecific chimeric antigen receptors and therapeutic uses thereof |
| WO2013126726A1 (en) | 2012-02-22 | 2013-08-29 | The Trustees Of The University Of Pennsylvania | Double transgenic t cells comprising a car and a tcr and their methods of use |
| CA3285826A1 (en) | 2012-02-22 | 2026-03-02 | The Trustees Of The University Of Pennsylvania | Compositions and methods for generating a persisting population of t cells useful for the treatment of cancer |
| AU2013256010B2 (en) * | 2012-05-04 | 2018-01-04 | Dana-Farber Cancer Institute, Inc. | Affinity matured anti-CCR4 humanized monoclonal antibodies and methods of use |
| UY35468A (es) | 2013-03-16 | 2014-10-31 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico de antígeno anti-cd19 |
| AU2015292744C1 (en) | 2014-07-21 | 2021-01-21 | Novartis Ag | Treatment of cancer using humanized anti-BCMA chimeric antigen receptor |
| RU2017125531A (ru) | 2014-12-19 | 2019-01-21 | Дана-Фарбер Кэнсер Инститьют, Инк. | Химерные антигенные рецепторы и способы их применения |
| KR102427334B1 (ko) * | 2016-04-01 | 2022-08-03 | 카이트 파마 인코포레이티드 | 키메라 항원 및 t 세포 수용체 및 사용 방법 |
| WO2018057585A1 (en) | 2016-09-21 | 2018-03-29 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric antigen receptor (car) that targets chemokine receptor ccr4 and its use |
-
2017
- 2017-09-20 WO PCT/US2017/052437 patent/WO2018057585A1/en not_active Ceased
- 2017-09-20 JP JP2019537030A patent/JP6908710B2/ja active Active
- 2017-09-20 US US16/334,724 patent/US11077178B2/en active Active
- 2017-09-20 EP EP17778069.9A patent/EP3515475B1/en not_active Revoked
- 2017-09-20 AU AU2017332161A patent/AU2017332161B9/en active Active
- 2017-09-20 CA CA3037518A patent/CA3037518A1/en active Pending
-
2021
- 2021-01-13 JP JP2021003261A patent/JP2021052804A/ja not_active Withdrawn
- 2021-06-21 US US17/353,054 patent/US11992519B2/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7857980B2 (ja) | Ｃｄ１９指向性キメラ抗原受容体および免疫療法におけるその使用 | |
| JP6779299B2 (ja) | 抗ｐｄ−ｌ１抗体およびその使用 | |
| JP2025000628A (ja) | ＮＫｐ４６結合タンパク質の可変領域 | |
| JP7162535B2 (ja) | 抗ｇｉｔｒ抗体およびその使用 | |
| CA3032581A1 (en) | Treatment of cancer using a chimeric antigen receptor in combination with an inhibitor of a pro-m2 macrophage molecule | |
| CN113784980B (zh) | 人源化抗Claudin18.2嵌合抗原受体及其用途 | |
| CA3095864A1 (en) | Bcma-car-t cells | |
| EA034142B1 (ru) | Биспецифические моновалентные диатела, которые способны связываться с cd123 и cd3, и их применения | |
| JP2019530431A5 (enExample) | ||
| JP2024519335A (ja) | がん免疫療法のための投薬レジメン | |
| JP2022527081A5 (enExample) | ||
| KR20240033025A (ko) | Bcma-지시된 세포 면역요법 조성물 및 방법 | |
| CN115768467A (zh) | 用于治疗癌症和感染的针对NKp46的抗体及其构建体 | |
| CA3244124A1 (en) | Anti-mesothelin antibodies and their uses | |
| AU2025204510A9 (en) | Car library and scFv manufacturing method | |
| JP2025524564A (ja) | Ｃｄ１９指向性がん免疫療法の投与レジメン | |
| US20220305056A1 (en) | Chimeric antigen receptor system and uses thereof | |
| CN115850484A (zh) | 一种靶向cd70的单链抗体及其应用 | |
| CA3208365A1 (en) | Cell therapy compositions and methods for modulating tgf-b signaling | |
| CA3211519A1 (en) | Anti-egfr single domain antibodies and therapeutic constructs | |
| WO2025238157A1 (en) | Multispecific binding agent suitable for use in cancer immune therapy | |
| KR20250117586A (ko) | 이중항체와 car-t의 병용 요법 | |
| WO2025232896A1 (zh) | 药物组合及用途 | |
| WO2024076864A2 (en) | Anti-ror1 antibodies and uses thereof | |
| TW202540162A (zh) | 含有結合至cldn18.2和cd3之雙特異性結合劑和抗vegfr2抗體之組合療法 |