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用于实体瘤免疫治疗的HER2特异性嵌合抗原受体T细胞的研究进展

Research progress on HER2-specific chimeric antigen receptor T cells for immunotherapy of solid tumors.

作者信息

Zhu Liaoliao, Liu Jingyi, Li Junqiang, Wang Nan, Zhao Yan, Su Haichuan

机构信息

State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Oncology, Tangdu Hospital, Air Force Medical University, Xi'an, Shannxi, China.

出版信息

Front Immunol. 2025 May 21;16:1514994. doi: 10.3389/fimmu.2025.1514994. eCollection 2025.

Abstract

Human epidermal growth factor receptor 2 (HER2) is highly expressed in various solid tumors, and its abnormal activation is closely associated with poor tumor prognosis, establishing it as a prominent target in contemporary research. The successful clinical treatment of multiple HER2-positive tumors with HER2 antibodies has prompted researchers to design chimeric antigen receptor T (CAR-T) cells targeting HER2 for solid tumor immunotherapy. To date, the development of CAR structures has progressed to the fifth generation, with most HER2-CAR-T cell structures being modified based on the second-generation CAR architecture. This review will delineate the structure and cytotoxic mechanism of HER2-CAR-T cells, elucidate the difficulties and optimization strategies for HER2-CAR-T cell therapy, and summarize recent clinical applications and advancements.

摘要

人表皮生长因子受体2(HER2)在多种实体瘤中高表达,其异常激活与肿瘤预后不良密切相关,这使其成为当代研究中的一个重要靶点。用HER2抗体成功地对多种HER2阳性肿瘤进行临床治疗,促使研究人员设计靶向HER2的嵌合抗原受体T(CAR-T)细胞用于实体瘤免疫治疗。迄今为止,CAR结构已发展到第五代,大多数HER2-CAR-T细胞结构是在第二代CAR结构的基础上进行改造的。本文综述将阐述HER2-CAR-T细胞的结构和细胞毒性机制,阐明HER2-CAR-T细胞治疗的难点及优化策略,并总结其近期的临床应用和进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9226/12133747/6fdb95e57317/fimmu-16-1514994-g001.jpg

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