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嵌合抗原受体T细胞(CAR-T)疗法在实体瘤治疗中的挑战与进展

The challenges and progress of CAR-T cell therapy in the treatment of solid tumors.

作者信息

Cui Kai, He Wanjun, Huang Na, Zhu Songshan, Jiang Dan, Yang Weiqiang, Zeng Yiwei, Farooq Muhammad Asad, Xu Guangxian

机构信息

Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, School of Medical Technology, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523808, Guangdong, China.

Dongguan Key Laboratory of Molecular Immunology and Cell Therapy, School of Medical Technology, Guangdong Medical University, Dongguan, 523808, China.

出版信息

Mol Cell Biochem. 2025 Jun 23. doi: 10.1007/s11010-025-05329-5.

Abstract

Current traditional cancer treatment methods include surgery, chemotherapy, radiotherapy, etc., which lack targeted killing functions and may damage normal tissues. Immunotherapy, targeted therapy, and personalized medicine have become promising methods for cancer treatment, providing more precise and effective treatment for patients. Among them, chimeric antigen receptor (CAR)-T cell therapy utilizes the immune system's T cells to recognize and attack tumor cells, showing promising therapeutic prospects. The FDA has approved CAR-T therapy for treating B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma, targeting CD-19 and B-cell maturation antigens. Despite success in hematologic cancers, CAR-T technology faces challenges in solid tumors, including a lack of reliable tumor-associated antigens, hypoxic cores, immunosuppressive tumor environments, enhanced reactive oxygen species, and decreased T cell infiltration. This review covers the advantages and disadvantages of various immunotherapy methods, highlights CAR-T therapy's evolution, summarizes CAR-T therapy's current status, lists promising therapeutic targets, and emphasizes the challenges CAR-T cell therapy faces.

摘要

当前传统的癌症治疗方法包括手术、化疗、放疗等,这些方法缺乏靶向杀伤功能,可能会损害正常组织。免疫疗法、靶向疗法和个性化医疗已成为有前景的癌症治疗方法,为患者提供了更精确有效的治疗。其中,嵌合抗原受体(CAR)-T细胞疗法利用免疫系统的T细胞识别并攻击肿瘤细胞,展现出了有前景的治疗前景。美国食品药品监督管理局(FDA)已批准CAR-T疗法用于治疗B细胞急性淋巴细胞白血病、大B细胞淋巴瘤和多发性骨髓瘤,其靶点为CD-19和B细胞成熟抗原。尽管CAR-T技术在血液系统癌症中取得了成功,但在实体瘤中面临挑战,包括缺乏可靠的肿瘤相关抗原、缺氧核心、免疫抑制性肿瘤环境、活性氧增加以及T细胞浸润减少。本综述涵盖了各种免疫疗法的优缺点,突出了CAR-T疗法的发展历程,总结了CAR-T疗法的现状,列出了有前景的治疗靶点,并强调了CAR-T细胞疗法面临的挑战。

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