The role of B7-H3-targeted chimeric antigen receptor T cell immunotherapy in solid tumors

doi:10.3877/cma.j.issn.2095-1221.2022.04.008

Abstract

Abstract:

The chimeric antigen receptor T (CAR-T) cell immunotherapy has achieved great success in the treatment of hematological malignancies. It brings new hope for the treatment of many malignancies. However, its application in solid tumours still faces enormous challenges. The suitable target antigen was the key to CAR-T cell immunotherapy for solid tumours. B7-H3 protein is highly expressed in a variety of solid tumours, and was related to tumour migration, infiltration and development. It is expected to become the most potential therapeutic target for CAR-T cell therapy in solid tumours. In this article, we summarize the research advance in CAR-T cell targets, B7-H3 target and CAR-T cells targeting B7-H3 in solid tumours, to provide a reference to carry out CAR-T cell solid tumour treatment research.

Key words: B7-H3, CAR-T, Immunotherapy, Solid tumors

Ying Luo, Ting Yan, Jin Chen. The role of B7-H3-targeted chimeric antigen receptor T cell immunotherapy in solid tumors[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2022, 12(04): 243-249.

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References 61

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肿瘤类型	临床试验识别符	标题	研究阶段	干预	发起者（合作者）	预计入组人数	主要完成时间
复发性/难治性胶质母细胞瘤	NCT04385173	Pilot Study of B7-H3 CAR-T in Treating Patients With Recurrent and Refractory Glioblastoma	I	B7-H3 CAR-T Temozolomide	浙江大学医学院附属第二医院（博源润盛制药（杭州）有限公司）	12	2022.5.1
卵巢癌	NCT05211557	Study of Fully Human B7H3 CAR-T in Treating Recurrent Malignant Ovarian Cancer	I/II	fhB7H3.CAR-Ts	徐州医科大学附属医院（徐州医科大学/IIT医药科技（江苏）有限公司）	15	2023.8.31
复发性胶质母细胞瘤	NCT04077866	B7-H3 CAR-T for Recurrent or Refractory Glioblastoma	I/II	Temozolomide B7-H3 CAR-T	浙江大学医学院附属第二医院（宁波市鄞州市人民医院/惠州市立中心医院/博源润盛制药（杭州）有限公司）	40	2024.6.1
难治性胶质母细胞瘤	NCT04077866	B7-H3 CAR-T for Recurrent or Refractory Glioblastoma	I/II	Temozolomide B7-H3 CAR-T	浙江大学医学院附属第二医院（宁波市鄞州市人民医院/惠州市立中心医院/博源润盛制药（杭州）有限公司）	40	2024.6.1
生殖细胞肿瘤、视网膜母细胞瘤、肝母细胞瘤等	NCT04483778	B7-H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults	I	second generation 4-1BBζ B7H3-EGFRt-DHFR second generation 4-1BBζ B7H3-EGFRt-DHFR （selected） and a second generation 4-1BBζ CD19-Her2tG	西雅图儿童医院（Julie Park, Seattle Children’s Hospital）	68	2025.12
胶质母细胞瘤	NCT05241392	Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma	I	B7-H3-targeting CAR-T cells	北京天坛医院	30	2024.12.31
肺癌	NCT03198052	PSCA/MUC1/TGFβ/HER2/Mesothelin/Lewis-Y/GPC3/AXL/EGFR/B7-H3/Claudin18.2-CAR-T Cells Immunotherapy Against Cancers	I	CAR-T cells targeting PSCA, MUC1, TGFβ, HER2, Mesothelin, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2, or B7-H3	广州医科大学附属第二医院（湖南兆泰永仁医疗创新有限公司/广东兆泰英威生物医药有限公司）	30	2022.8.1
癌症
免疫疗法CAR-T Cell
中枢神经系统肿瘤（弥漫性内源性脑桥胶质瘤、弥漫性中线胶质瘤等）	NCT04185038	Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors	I	SCRI-CARB7H3 （s）; B7H3-specific chimeric antigen receptor （CAR） T cel	西雅图儿童医院（Julie Park, Seattle Children's Hospital）	90	2026.5
上皮性卵巢癌	NCT04670068	Phase I Study of Autologous CAR T-Cells Targeting the B7-H3 Antigen in Recurrent Epithelial Ovarian	I	CAR.B7-H3，Fludarabine，Cyclophosphamide	UNC Lineberger综合癌症中心（美国国立卫生研究院(NIH)）	21	2025.2
恶性黑色素瘤	NCT05190185	A Clinical Trial of TAA06 Injection in Advanced Solid Tumors	I	TAA06 injection（TAA06注射液是针对B7-H3的CART注射液）	人源生物治疗（苏州）有限公司（河北医科大学第四医院免疫科）	18	2023.12.1
肺癌或结直肠癌	NCT05190185		I	TAA06 injection（TAA06注射液是针对B7-H3的CART注射液）	人源生物治疗（苏州）有限公司（河北医科大学第四医院免疫科）	18	2023.12.1
晚期胰腺癌	NCT05143151	CD276 targeted Chimeric Antigen Receptor T Cells in Treatment With Advanced Pancreatic Cancer	I/II	CD276 CAR-T cells	深圳大学附属医院	10	2024.6
实体瘤（如脑肿瘤，尤文氏肉瘤）	NCT04432649	Targeting CD276 （B7-H3） Positive Solid Tumors by 4SCAR-276	I/II	4SCAR-276（4th generation CD276-specific chimeric antigen receptor）	深圳市基因免疫医学研究所（中山大学/深圳市儿童医院）	100	2023.5.1
神经母细胞瘤	NCT04637503	4SCAR-T Therapy Targeting GD2, PSMA and CD276 for Treating Neuroblastoma	I/II	GD2, PSMA CD276 CAR-T cells	深圳市基因免疫医学研究所（深圳市儿童医院）	100	2020.11.19
肝癌	NCT05323201	Study Of B7H3 CAR-T Cells in Treating Advanced Liver Cancer	I/II	fhB7H3-CAR-Ts, Fludarabine, Cyclophosphamide	徐州医科大学附属医院（徐州医科大学/IIT医疗科技有限公司）	15	2024.2.10

肿瘤类型	临床试验识别符	标题	研究阶段	干预	发起者（合作者）	预计入组人数	主要完成时间
复发性/难治性胶质母细胞瘤	NCT04385173	Pilot Study of B7-H3 CAR-T in Treating Patients With Recurrent and Refractory Glioblastoma	I	B7-H3 CAR-T Temozolomide	浙江大学医学院附属第二医院（博源润盛制药（杭州）有限公司）	12	2022.5.1
卵巢癌	NCT05211557	Study of Fully Human B7H3 CAR-T in Treating Recurrent Malignant Ovarian Cancer	I/II	fhB7H3.CAR-Ts	徐州医科大学附属医院（徐州医科大学/IIT医药科技（江苏）有限公司）	15	2023.8.31
复发性胶质母细胞瘤	NCT04077866	B7-H3 CAR-T for Recurrent or Refractory Glioblastoma	I/II	Temozolomide B7-H3 CAR-T	浙江大学医学院附属第二医院（宁波市鄞州市人民医院/惠州市立中心医院/博源润盛制药（杭州）有限公司）	40	2024.6.1
难治性胶质母细胞瘤	NCT04077866	B7-H3 CAR-T for Recurrent or Refractory Glioblastoma	I/II	Temozolomide B7-H3 CAR-T	浙江大学医学院附属第二医院（宁波市鄞州市人民医院/惠州市立中心医院/博源润盛制药（杭州）有限公司）	40	2024.6.1
生殖细胞肿瘤、视网膜母细胞瘤、肝母细胞瘤等	NCT04483778	B7-H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults	I	second generation 4-1BBζ B7H3-EGFRt-DHFR second generation 4-1BBζ B7H3-EGFRt-DHFR （selected） and a second generation 4-1BBζ CD19-Her2tG	西雅图儿童医院（Julie Park, Seattle Children’s Hospital）	68	2025.12
胶质母细胞瘤	NCT05241392	Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma	I	B7-H3-targeting CAR-T cells	北京天坛医院	30	2024.12.31
肺癌	NCT03198052	PSCA/MUC1/TGFβ/HER2/Mesothelin/Lewis-Y/GPC3/AXL/EGFR/B7-H3/Claudin18.2-CAR-T Cells Immunotherapy Against Cancers	I	CAR-T cells targeting PSCA, MUC1, TGFβ, HER2, Mesothelin, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2, or B7-H3	广州医科大学附属第二医院（湖南兆泰永仁医疗创新有限公司/广东兆泰英威生物医药有限公司）	30	2022.8.1
癌症
免疫疗法CAR-T Cell
中枢神经系统肿瘤（弥漫性内源性脑桥胶质瘤、弥漫性中线胶质瘤等）	NCT04185038	Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors	I	SCRI-CARB7H3 （s）; B7H3-specific chimeric antigen receptor （CAR） T cel	西雅图儿童医院（Julie Park, Seattle Children's Hospital）	90	2026.5
上皮性卵巢癌	NCT04670068	Phase I Study of Autologous CAR T-Cells Targeting the B7-H3 Antigen in Recurrent Epithelial Ovarian	I	CAR.B7-H3，Fludarabine，Cyclophosphamide	UNC Lineberger综合癌症中心（美国国立卫生研究院(NIH)）	21	2025.2
恶性黑色素瘤	NCT05190185	A Clinical Trial of TAA06 Injection in Advanced Solid Tumors	I	TAA06 injection（TAA06注射液是针对B7-H3的CART注射液）	人源生物治疗（苏州）有限公司（河北医科大学第四医院免疫科）	18	2023.12.1
肺癌或结直肠癌	NCT05190185		I	TAA06 injection（TAA06注射液是针对B7-H3的CART注射液）	人源生物治疗（苏州）有限公司（河北医科大学第四医院免疫科）	18	2023.12.1
晚期胰腺癌	NCT05143151	CD276 targeted Chimeric Antigen Receptor T Cells in Treatment With Advanced Pancreatic Cancer	I/II	CD276 CAR-T cells	深圳大学附属医院	10	2024.6
实体瘤（如脑肿瘤，尤文氏肉瘤）	NCT04432649	Targeting CD276 （B7-H3） Positive Solid Tumors by 4SCAR-276	I/II	4SCAR-276（4th generation CD276-specific chimeric antigen receptor）	深圳市基因免疫医学研究所（中山大学/深圳市儿童医院）	100	2023.5.1
神经母细胞瘤	NCT04637503	4SCAR-T Therapy Targeting GD2, PSMA and CD276 for Treating Neuroblastoma	I/II	GD2, PSMA CD276 CAR-T cells	深圳市基因免疫医学研究所（深圳市儿童医院）	100	2020.11.19
肝癌	NCT05323201	Study Of B7H3 CAR-T Cells in Treating Advanced Liver Cancer	I/II	fhB7H3-CAR-Ts, Fludarabine, Cyclophosphamide	徐州医科大学附属医院（徐州医科大学/IIT医疗科技有限公司）	15	2024.2.10

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