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中华细胞与干细胞杂志(电子版) ›› 2022, Vol. 12 ›› Issue (04) : 243 -249. doi: 10.3877/cma.j.issn.2095-1221.2022.04.008

综述

靶向B7-H3的CAR-T细胞免疫疗法在实体瘤中的应用研究进展
罗应1, 晏婷1, 陈津1,()   
  1. 1. 海南医学院第二附属医院临床医学研究所
  • 收稿日期:2022-03-08 出版日期:2022-08-01
  • 通信作者: 陈津
  • 基金资助:
    海南省重点研发项目(ZDYF2022SHFZ133); 海南省自然科学基金(822MS173)

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

Ying Luo1, Ting Yan1, Jin Chen1,()   

  1. 1. Institute of Clinical Medicine, the Second Affiliated Hospital of Hainan Medical University, Hai Kou 570311, China
  • Received:2022-03-08 Published:2022-08-01
  • Corresponding author: Jin Chen
引用本文:

罗应, 晏婷, 陈津. 靶向B7-H3的CAR-T细胞免疫疗法在实体瘤中的应用研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2022, 12(04): 243-249.

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

嵌合抗原受体T (CAR-T)细胞免疫治疗在血液系统恶性肿瘤治疗中取得了显著的成效,为恶性肿瘤治疗带来了曙光,而在实体瘤中的应用面临着巨大的挑战。选择合适的治疗靶点是CAR-T细胞治疗实体瘤的关键。B7-H3蛋白在多种实体瘤中表达量高,与肿瘤的迁移、浸润和发展有关,有望成为实体瘤CAR-T细胞治疗最具潜力的治疗靶点。本文就CAR-T细胞靶点、B7-H3靶点及靶向B7-H3的CAR-T细胞在实体瘤中的研究进展进行总结,为未来CAR-T细胞治疗实体瘤研究提供参考。

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.

图1 CAR-T细胞肿瘤免疫治疗示意图注:从患者外周血中提取外周血单个核细胞,筛选出外周血单个核细胞中的T细胞进行扩增,然后转导含有CAR的慢病毒,将含有CAR的T细胞大量培养,收集细胞,鉴定其合格后,回输到患者体内。CAR-T细胞在体内与含有相应抗原的肿瘤靶细胞相结合,产生杀伤作用,从而起到治疗肿瘤的效果;CAR为嵌合抗原受体
图2 B7-H3 CAR-T细胞在实体瘤中的应用注:B7-H3 CAR-T细胞已应用于多种类型的实体瘤,如母胶质细胞瘤、黑色素瘤和淋巴癌等,而且取得令人满意的成功,未来它也将应用在更多实体瘤中,探索更多的治疗潜力
表1 正在实体瘤中进行B7-H3 CAR-T细胞治疗的临床实验
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
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
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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