嵌合抗原受体-T细胞免疫治疗在血液系统恶性肿瘤中的应用进展

Application of CAR-T Cell Immunotherapy in the Treatment of Hematological Malignancy

嵌合抗原受体(CAR)将单链抗体可变区与T细胞的活化基序相融合,使其修饰的T细胞具有非主要组织相容性复合物(MHC)限制性识别肿瘤抗原及杀伤靶细胞的双重功能。CAR细胞内区的结构从表达单一信号分子的第1代,发展为添加1个及2个以上共刺激分子的第2代和第3代以及增加了编码CAR和/或其启动子、自杀基因等的第4代,使T细胞在体内的存活时间和杀伤能力明显增强且能够调控。本文就CAR-T细胞免疫治疗的原理、在血液系统恶性肿瘤中的应用以及主要不良反应和应对措施进行分析,发现应用CAR-T细胞免疫治疗多种血液系统恶性肿瘤取得了较好临床疗效,其中以靶向CD19的CAR-T细胞免疫治疗疗效尤为突出,患者的生存期延长、生活质量改善并且不良反应较少。CAR-T细胞免疫治疗的主要不良反应是脱靶效应和细胞因子释放综合征,需要引起临床足够重视。

Chimeric antigen receptor（CAR）connects single - chain variable fragment and activation motif of T cells, which allows modified T cells possess dual functions of recognizing tumor antigens in an MHC unrestricted way and killing the target cells. The intracellular structures of CAR has changed over time,from the first generation with the expression of single signal molecule,to the second and third generation adding one or two and multiple costimulatory endodomains,and to the fourth generation combining with the domains of coding CAR and/ or the promoter,and suicide gene. They enhance and regulate the persistence and cytotoxicity of modified T cells. This paper summarized the available data on the principle of CAR-T cell immunotherapy,its application in the treatment of hematological malignancy,and the main adverse reactions and response measures. It was found that chimeric antigen receptor - T（CAR-T）cells have received better therapeutic effect in many types of hematological malignancy,remarkably for the CAR-T cell immunotherapy targeting CD19;patients who adopt cell immunotherapy have prolonged survival,improved quality of life,and less adverse reactions. The main adverse reactions of CAR-T cell immunotherapy are on - target toxicity and cytokine release syndrome,which must be paid more attention.