CAR-T细胞治疗实体瘤的挑战与应对策略

Challenges and Strategies of CAR-T Cell Therapy for Solid Tumors

嵌合抗原受体T细胞(CAR-T)作为肿瘤免疫治疗的新疗法,已在多种血液肿瘤的临床治疗中取得了突破性进展,但用于实体瘤的治疗仍面临着诸多挑战。本文根据CAR-T细胞在实体瘤中的应用情况,总结其疗效不佳的原因,包括缺乏肿瘤特异性靶抗原、T细胞的转运及肿瘤浸润障碍、肿瘤微环境的免疫抑制等;并以此分析可行的解决策略,如提高肿瘤细胞特异性、提高对实体瘤的转运及浸润、解除免疫抑制以及提高CAR-T细胞在体内的持久性等,以期为后续CAR-T细胞治疗实体肿瘤研究提供思路。

Chimeric antigen receptor T-cell(CAR-T), as a new therapy for tumor immunotherapy, has made breakthroughs in the clinical treatment of a variety of blood tumors, but the treatment of solid tumors still faces many challenges. This article focuses on the application progress of CAR-T cell therapy in solid tumors, and clearly points out that the lack of tumor specific target antigens, the obstacle of T cell transport and tumor infiltration, and the immunosuppression of tumor microenvironment are the major challenges that lead to poor CAR-T treatment of solid tumors. At the same time, it summarizes and analyzes the feasible solutions from the aspects of improving the specificity of tumor cells, improving the transport and infiltration of solid tumors, relieving immunosuppression and improving the durability of CART cells in vivo, so as to lay a theoretical foundation for the follow-up research on CAR-T cells in the treatment of solid tumors.