肿瘤细胞治疗研究
英文原题：Barriers and solutions for CAR-T therapy in solid tumors.
Barriers and solutions for CAR-T therapy in solid tumors.
嵌合抗原受体（CAR）-T细胞疗法已成为一种变革性的癌症治疗方法，尤其在血液系统恶性肿瘤中。
嵌合抗原受体（CAR）-T细胞疗法已成为一种变革性的癌症治疗手段，尤其是在血液系统恶性肿瘤中。然而，针对实体瘤开发有效CAR-T疗法的障碍，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，阻碍了其可扩展性和更广泛的临床实施。为克服这些障碍，近年来已开发出多种策略，例如优化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体内原位编程CAR-T细胞。在此，我们讨论当前CAR-T细胞疗法在实体瘤中的障碍与潜在策略。最后，我们就这些先进策略以推动CAR-T细胞疗法更广泛的临床采用提出展望。
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.
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