细胞治疗的典范：嵌合抗原受体T细胞疗法

Cell therapy’s poster child: Chimeric antigen receptor T cell therapy

摘要:

嵌合抗原受体T (CAR-T) 细胞疗法是一种利用合成受体特异性靶向抗原的过继性细胞疗法(ACT)，目前在血液肿瘤的治疗中有极大的临床应用价值。虽然美国食品药品监督管理局 (FDA) 已经批准两款CAR-T药物上市，但CAR-T疗法在治疗过程中仍然存在一些副作用，如细胞因子释放综合征 (CRS)、神经毒性、B细胞功能缺失等。同时，CAR-T疗法在实体瘤治疗中的效果甚微，主要原因是缺乏特异性靶点以及肿瘤微环境对CAR-T细胞功能的抑制等。文中将从CAR的结构设计、临床应用、合成生物学对新型CAR的优化来阐述应用CAR-T细胞疗法治疗肿瘤所面临的挑战及广阔前景。

Abstract:

Chimeric antigen receptor T (CAR-T) cell therapy, which adoptively transfers engineered T cells expressing synthetic receptors to target specific antigens, has achieved great clinical success in treating hematological malignancies. Though FDA has approved two CAR-T products, CAR-T therapy can cause some side effects, such as cytokine release syndrome (CRS), neurotoxicity and B cell aplasia. Meanwhile, lacking tumor specific antigen and the suppressive tumor environment limit the efficacy of CAR-T therapy in solid tumor. This review focuses on the structural components, clinical applications and synthetic biology approaches on CAR-T cell design, and summarizes the challenges and perspectives of CAR-T therapy as a revolutionary cancer immunotherapy.