嵌合抗原受体修饰T细胞疗法:过去、现在和未来

Chimeric antigen receptor-modified T cell therapy:past,present and future

嵌合抗原受体修饰T细胞(chimeric antigen receptor-modified T cells,CAR-T)疗法经过30多年的发展已日趋成熟为一种新型治疗方式,特别是CAR-T细胞在血液瘤治疗中取得了巨大成功。目前已经有8款CAR-T产品获得美国食品药品监督管理局(FDA)批准用于血液肿瘤的治疗。除了在血液肿瘤中的应用,CAR-T细胞在实体瘤治疗中的研究更是在如火如荼地进行,但是目前的临床疗效仍不尽如人意,亟待开发出新一代CAR-T细胞疗法。此外,CAR-T细胞疗法的应用也在不断拓展,不仅涵盖了恶性肿瘤治疗,也延伸至感染性疾病、自身免疫性疾病、器官移植排斥、衰老、纤维化等非肿瘤疾病的治疗。本文将主要综述CAR-T细胞疗法的发展历程和近年来的研究进展,特别是CAR-T细胞疗法在实体瘤中的应用,并对该疗法的未来发展作一展望。

After more than 30 years of development,chimeric antigen receptor-modified T cells(CAR-T)therapy has matured into a novel therapeutic modality.Currently,eight chimeric antigen receptor-modified T cells(CAR-T)products have been approved by the U.S.Food and Drug Administration(FDA)for the therapy of liquid tumors because of great success of CAR-T cells in the treatment of hematological cancers.In addition to hematological malignancies,the studies of CAR-T cell therapy in solid tumors are in full swing,but its therapeutic efficacy remains unsatisfied,and it is urgent to develop a new generation of CAR-T cell therapy.Moreover,the application of CAR-T cell therapy is also constantly expanding,not only covering the treatment of malignant tumors,but also extending to the therapy of infectious diseases,autoimmune diseases,organ transplant rejection,aging,fibrosis and other non-tumor diseases.This paper will review the development of CAR-T cell therapy and the research progresses in recent years,especially CAR-T cell therapy in solid tumors,and give an outlook on the future development of this therapy.