Tu Zhihao, Chen Yuelin, Zhang Zhimi, Meng Wanrong, Li Ling
Department of Stomatology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Head and Neck Oncology, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.
Cancer Gene Ther. 2025 Jun 27. doi: 10.1038/s41417-025-00931-7.
Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative approach for cancer treatment, particularly in hematologic malignancies. However, barriers in the development of effective CAR-T therapies for solid tumors, including antigenic escape, tumor immunosuppressive microenvironments, severe toxicities, and limitations in preclinical models, hinder its scalability and broader clinical implementation. To overcome these barriers, strategies have been developed in recent years, such as optimizing CAR designs, enhancing CAR-T cell infiltration, neutralizing immunosuppressive cells, remodeling metabolism of CAR-T cells, eliminating antigen escape, mitigating toxicities, advancing preclinical models, and in situ programming CAR-T cells. Here, we discuss current barriers and potential strategies for CAR-T cell therapy in solid tumors. Ultimately, we present perspectives on these advanced strategies for broader clinical adoption of CAR-T cell therapy.
嵌合抗原受体(CAR)-T细胞疗法已成为癌症治疗的一种变革性方法,尤其是在血液系统恶性肿瘤中。然而,实体瘤有效CAR-T疗法开发过程中存在的障碍,包括抗原逃逸、肿瘤免疫抑制微环境、严重毒性以及临床前模型的局限性,阻碍了其扩大规模和更广泛的临床应用。为克服这些障碍,近年来已开发出多种策略,如优化CAR设计、增强CAR-T细胞浸润、中和免疫抑制细胞、重塑CAR-T细胞代谢、消除抗原逃逸、减轻毒性、改进临床前模型以及原位编程CAR-T细胞。在此,我们讨论实体瘤中CAR-T细胞疗法当前存在的障碍和潜在策略。最终,我们就这些先进策略发表观点,以期CAR-T细胞疗法能更广泛地应用于临床。