嵌合抗原受体T细胞技术的介绍及研究进展

嵌合抗原受体T细胞免疫疗法(CAR-T)是一种过继性细胞免疫治疗(ACI),并在近年来得到迅猛发展.通过导入外源基因使T细胞表达嵌合抗原受体(CAR),在肿瘤免疫效应上表现高特异性、靶向性、MHC非限制性等特点.目前,CAR-T技术已经发展至第三代,即表达于T细胞表面的CAR分子由胞外抗原识别区和胞内双信号产生区构成,该结构保障了CAR-T细胞与靶细胞接触时收到双信号的激活以发挥最大的抗肿瘤效应.但同时CAR-T细胞在临床应用中也存在如脱靶效应、细胞因子风暴等风险,需要急待解决.

Introduction and research progress of chimeric antigen receptor T cells

Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T)is one of the adoptive cellular immunotherapies against malignancies.CAR-T cell therapy has been developing rapidly in recent years.By the use of genetic modification techniques,T-cells can express Chimeric Antigen Receptor (CAR) molecule,working with higher specificity,targeting,and without MHC restriction,etc.So far,CAR-T technology has reached its third generation.The CAR molecule,expressed on the membrane of T-cell,is constructed by extracellular antigen-binding domain and intracellular double-signal domain.This structure ensures that the two signals for T-cell activation are provided as soon as CAR molecule binds with target tumor antigen.This can strictly improve antitumor effect of CAR-T cell.However,CAR-T cell application has some clinical drawbacks,such as on-target offtumor effect,cytokine storm.