Advance in chimeric antigen receptor T-cell therapy for glioblastoma

doi:10.3969/j.issn.1672-6731.2026.08.016

Abstract

Abstract:

Glioblastoma (GBM) has an extremely poor prognosis, and chimeric antigen receptor T-cell (CAR-T) therapy offers new hope for its treatment. This review systematically discusses the research progress of CAR-T therapy for GBM, analyzing the major challenges related to the blood brain barrier, the immunosuppressive tumor microenvironment, and the high heterogeneity of tumor antigens and antigen escape. It also summarizes opportunities including target innovation and multi-targeting strategies, breakthroughs in local administration routes, and combination therapy approaches, with the aim of providing a reference for optimizing CAR-T therapy strategies and improving patient outcomes in GBM.

Key words: Glioblastoma, Receptors, chimeric antigen, T-lymphocytes, Immunotherapy, Tumor microenvironment, Review

摘要：

胶质母细胞瘤预后极差，嵌合抗原受体T细胞（CAR-T）治疗带来新希望。本文总结CAR-T细胞治疗在胶质母细胞瘤中的应用进展，分析其在血脑屏障阻碍、免疫抑制性肿瘤微环境、肿瘤抗原高度异质性及免疫逃逸等方面的主要挑战，以及靶点创新与多靶点策略、局部给药途径突破、联合治疗策略等方面的主要机遇，拟为优化胶质母细胞瘤的CAR-T细胞治疗策略、改善患者预后提供参考。

关键词: 胶质母细胞瘤, 嵌合抗原受体, T淋巴细胞, 免疫疗法, 肿瘤微环境, 综述

CLC Number:

R739.41

Feng YUAN, Ying-shuai WANG, Qiu-wei HUA, Xing-liang DAI, Qiang CAI, Xue-jun YANG. Advance in chimeric antigen receptor T-cell therapy for glioblastoma[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2026, 26(8): 924-933.

苑锋, 王英帅, 华秋伟, 代兴亮, 蔡强, 杨学军. 嵌合抗原受体T细胞治疗在胶质母细胞瘤中的应用进展[J]. 中国现代神经疾病杂志, 2026, 26(8): 924-933.

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URL: https://journal11.magtechjournal.com/cjcnn/EN/10.3969/j.issn.1672-6731.2026.08.016

https://journal11.magtechjournal.com/cjcnn/EN/Y2026/V26/I8/924

Figures/Tables 4

References 76

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文献来源	研究机构	试验编号	试验阶段	患者	病例数	干预	试验时间	研究结果
Morgan等^[52](2012)	NCI	NCT01454596	Ⅰ~Ⅱ期	EGFRvIII⁺胶质瘤	18	EGFRvIIICAR-T	2012年5月至2019年1月	未公布
Bagley等^[53](2024)	University of Pennsylvania	NCT03726515	Ⅰ期	新诊断EGFRvIII⁺、MGMT未甲基化GBM	7	EGFRvIIICAR-T联合帕博利珠单抗	2019年3月至2021年2月	未观察到剂量限制性毒性; 中位无进展生存期5.2个月(90%CI: 2.9~6.0)和中位总生存期11.8个月(90%CI: 9.2~14.2)
未发表	City of Hope Medical Center	NCT04003649	Ⅰ期	复发/难治性GBM	20	IL-13Rα2 CAR-T联合或不联合纳武利尤单抗和伊匹木单抗	2019年12月至2026年9月	未公布
未发表	UWELL Biopharma	NCT04717999	Ⅰ期	复发GBM	20	NKG2D CAR-T	2021年9月至2023年12月	未公布
未发表	Stanford University	NCT05474378	Ⅰ期	复发GBM	39	B7-H3 CAR-T	2022年7月至2026年8月	未公布
未发表	UNC Lineberger Comprehensive Cancer Center	NCT05366179	Ⅰ期	复发/难治性GBM	36	B7-H3 CAR-T	2022年9月至2030年5月	未公布
Bagley等^[54](2024)	University of Pennsylvania	NCT05168423	Ⅰ期	EGFR扩增复发GBM	67	EGFR-IL-13Rα2 CAR-T	2023年2月至2039年12月	2/6例出现早发性神经毒性, 1/6例发生剂量限制性毒性; 6例肿瘤均于治疗早期体积缩小, 但未达到客观缓解标准
Choi等^[20](2024)	Massachusetts General Hospital	NCT05660369	Ⅰ期	新诊断/复发GBM	27	CARv3-TEAM-E T	2023年3月至2027年9月	未观察到剂量限制性毒性; 2例疗效短暂, 1例短期随访(150d内)持久缓解
未发表	Chimeric Therapeutics	NCT05627323	Ⅰ期	MMP-2+复发/进展性GBM	42	CHM-1101 CAR-T	2023年6月至2041年1月	未公布
未发表	University of Florida	NCT05353530	Ⅰ期	CD70+GBM	39	8R-70 CAR-T	2023年7月至2042年12月	未公布
Nejo等^[55](2026)	University of California	NCT06186401	Ⅰ期	EGFRvIII⁺GBM	20	E-SYNC CAR-T	2024年4月至2027年12月	未公布
未发表	University of Florida	NCT06946680	Ⅰ期	CD70+成人GBM和儿童高级别胶质瘤	24	8R-70 CAR-T	2025年3月至2045年12月	未公布
未发表	City of Hope Medical Center	NCT06815029	Ⅰ期	复发/进展性GBM	27	TGF-β R2KO/IL-13Rα2 CAR-T	2025年6月至2030年10月	未公布
未发表	University of Pennsylvania	NCT07209241	Ⅰ期	EGFR扩增复发GBM	12	CAR-EGFR-IL-13Rα2 T	2025年11月至2042年11月	未公布
未发表	Baylor College of Medicine	NCT06815432	Ⅰ期	GPC3+复发GBM	27	GPC3 CAR-T	2025年12月至2044年12月	未公布

文献来源	研究机构	试验编号	试验阶段	患者	病例数	干预	试验时间	研究结果
Morgan等^[52](2012)	NCI	NCT01454596	Ⅰ~Ⅱ期	EGFRvIII⁺胶质瘤	18	EGFRvIIICAR-T	2012年5月至2019年1月	未公布
Bagley等^[53](2024)	University of Pennsylvania	NCT03726515	Ⅰ期	新诊断EGFRvIII⁺、MGMT未甲基化GBM	7	EGFRvIIICAR-T联合帕博利珠单抗	2019年3月至2021年2月	未观察到剂量限制性毒性; 中位无进展生存期5.2个月(90%CI: 2.9~6.0)和中位总生存期11.8个月(90%CI: 9.2~14.2)
未发表	City of Hope Medical Center	NCT04003649	Ⅰ期	复发/难治性GBM	20	IL-13Rα2 CAR-T联合或不联合纳武利尤单抗和伊匹木单抗	2019年12月至2026年9月	未公布
未发表	UWELL Biopharma	NCT04717999	Ⅰ期	复发GBM	20	NKG2D CAR-T	2021年9月至2023年12月	未公布
未发表	Stanford University	NCT05474378	Ⅰ期	复发GBM	39	B7-H3 CAR-T	2022年7月至2026年8月	未公布
未发表	UNC Lineberger Comprehensive Cancer Center	NCT05366179	Ⅰ期	复发/难治性GBM	36	B7-H3 CAR-T	2022年9月至2030年5月	未公布
Bagley等^[54](2024)	University of Pennsylvania	NCT05168423	Ⅰ期	EGFR扩增复发GBM	67	EGFR-IL-13Rα2 CAR-T	2023年2月至2039年12月	2/6例出现早发性神经毒性, 1/6例发生剂量限制性毒性; 6例肿瘤均于治疗早期体积缩小, 但未达到客观缓解标准
Choi等^[20](2024)	Massachusetts General Hospital	NCT05660369	Ⅰ期	新诊断/复发GBM	27	CARv3-TEAM-E T	2023年3月至2027年9月	未观察到剂量限制性毒性; 2例疗效短暂, 1例短期随访(150d内)持久缓解
未发表	Chimeric Therapeutics	NCT05627323	Ⅰ期	MMP-2+复发/进展性GBM	42	CHM-1101 CAR-T	2023年6月至2041年1月	未公布
未发表	University of Florida	NCT05353530	Ⅰ期	CD70+GBM	39	8R-70 CAR-T	2023年7月至2042年12月	未公布
Nejo等^[55](2026)	University of California	NCT06186401	Ⅰ期	EGFRvIII⁺GBM	20	E-SYNC CAR-T	2024年4月至2027年12月	未公布
未发表	University of Florida	NCT06946680	Ⅰ期	CD70+成人GBM和儿童高级别胶质瘤	24	8R-70 CAR-T	2025年3月至2045年12月	未公布
未发表	City of Hope Medical Center	NCT06815029	Ⅰ期	复发/进展性GBM	27	TGF-β R2KO/IL-13Rα2 CAR-T	2025年6月至2030年10月	未公布
未发表	University of Pennsylvania	NCT07209241	Ⅰ期	EGFR扩增复发GBM	12	CAR-EGFR-IL-13Rα2 T	2025年11月至2042年11月	未公布
未发表	Baylor College of Medicine	NCT06815432	Ⅰ期	GPC3+复发GBM	27	GPC3 CAR-T	2025年12月至2044年12月	未公布

文献来源	研究机构	试验编号	试验阶段	患者	病例数	干预	试验时间	研究结果
未发表	首都医科大学三博脑科医院	NCT02844062	Ⅰ期	复发GBM	20	EGFRvIII CAR-T	2016年7月至2019年7月	未公布
未发表	空军军医大学西京医院	NCT04045847	Ⅰ期	复发GBM	31	CD147 CAR-T	2019年5月至2022年5月	未公布
未发表	复旦大学	NCT05131763	Ⅰ期	NKG2DL+复发/难治性实体瘤	3	NKG2D CAR-T	2021年3月至2023年12月	未公布
未发表	首都医科大学附属北京天坛医院	NCT05241392	Ⅰ期	复发GBM	30	B7-H3 CAR-T	2022年1月至2026年12月	未公布
未发表	上海先博生物科技有限公司	NCT05868083	Ⅰ期	复发GBM	16	SNC-109 CAR-T	2022年6月至2024年8月	未公布
未发表	浙江大学医学院附属第二医院	NCT04077866	Ⅰ期	复发/难治性GBM	40	B7-H3 CAR-T联合替莫唑胺	2023年6月至2025年8月	未公布
未发表	首都医科大学附属北京天坛医院	NCT05577091	Ⅰ期	复发GBM	10	Tris-CAR-T	2023年9月至2032年11月	未公布
未发表	清华大学附属北京清华长庚医院	NCT05802693	Ⅰ期	复发GBM	22	EGFRvIII CAR-T	2023年11月至2025年11月	未公布
未发表	北京艺妙神州生物医药股份有限公司	NCT06691308	Ⅰ期	CD276+复发/进展性GBM	6	WL276 CAR-T	2024年11月至2027年5月	未公布
未发表	深圳市免疫基因治疗研究院	NCT07180927	Ⅰ期	DLL3+胶质瘤	30	DLL3 CAR-T	2025年9月至2029年9月	未公布
未发表	浙江大学医学院附属第二医院	NCT07193628	Ⅰ期	复发/难治性GBM	14	B7-H3/IL-13Rα2CAR-T	2025年9月至2028年12月	未公布

文献来源	研究机构	试验编号	试验阶段	患者	病例数	干预	试验时间	研究结果
未发表	首都医科大学三博脑科医院	NCT02844062	Ⅰ期	复发GBM	20	EGFRvIII CAR-T	2016年7月至2019年7月	未公布
未发表	空军军医大学西京医院	NCT04045847	Ⅰ期	复发GBM	31	CD147 CAR-T	2019年5月至2022年5月	未公布
未发表	复旦大学	NCT05131763	Ⅰ期	NKG2DL+复发/难治性实体瘤	3	NKG2D CAR-T	2021年3月至2023年12月	未公布
未发表	首都医科大学附属北京天坛医院	NCT05241392	Ⅰ期	复发GBM	30	B7-H3 CAR-T	2022年1月至2026年12月	未公布
未发表	上海先博生物科技有限公司	NCT05868083	Ⅰ期	复发GBM	16	SNC-109 CAR-T	2022年6月至2024年8月	未公布
未发表	浙江大学医学院附属第二医院	NCT04077866	Ⅰ期	复发/难治性GBM	40	B7-H3 CAR-T联合替莫唑胺	2023年6月至2025年8月	未公布
未发表	首都医科大学附属北京天坛医院	NCT05577091	Ⅰ期	复发GBM	10	Tris-CAR-T	2023年9月至2032年11月	未公布
未发表	清华大学附属北京清华长庚医院	NCT05802693	Ⅰ期	复发GBM	22	EGFRvIII CAR-T	2023年11月至2025年11月	未公布
未发表	北京艺妙神州生物医药股份有限公司	NCT06691308	Ⅰ期	CD276+复发/进展性GBM	6	WL276 CAR-T	2024年11月至2027年5月	未公布
未发表	深圳市免疫基因治疗研究院	NCT07180927	Ⅰ期	DLL3+胶质瘤	30	DLL3 CAR-T	2025年9月至2029年9月	未公布
未发表	浙江大学医学院附属第二医院	NCT07193628	Ⅰ期	复发/难治性GBM	14	B7-H3/IL-13Rα2CAR-T	2025年9月至2028年12月	未公布

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