基于不同靶点及治疗策略的嵌合抗原受体T细胞疗法在实体瘤中应用的研究进展

Advance in research on application of chimeric antigen receptor T cell therapy based on different targets and therapeutic strategies to solid tumors

嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T)是利用基因工程技术,将患者自身的T细胞分离体外,并在其表面表达一个能特异性识别肿瘤表面抗原的单链抗体(single chain antibody fragment,ScFv)区域,实现精准靶向杀伤癌细胞。作为一种新型细胞免疫疗法,CAR-T在治疗血液肿瘤方面取得了较大突破,但由于肿瘤特异性抗原缺乏与抑制性肿瘤免疫微环境等诸多因素的限制,CAR-T疗法在治疗实体瘤领域仍面临巨大挑战。近年,在CAR-T靶点选取与优化、CAR分子结构设计及打破肿瘤微环境免疫抑制等方面摸索出了多种方案,并有部分候选产品进入临床试验阶段。本文就CAR-T细胞疗法在实体瘤中应用的最新研究进展作一综述。

As a novel cellular immunotherapy,chimeric antigen receptor T cell(CAR-T)therapy is a major breakthroughs in the treatment of hematological malignancies.In this therapy,the T cells of patients were isolated by gene engineering technique,on the surface of which a single chain antibody fragment(ScFv)domain specifically recognizing tumor surface antigen is expressed to target and kill tumor cells precisely.However,due to the multiple factors such as lack in tumor-specific antigen and microenvironment of immunosuppressive tumor,CAR-T cell therapy faces enormous challenges in the field of treatment of solid tumors.In recent years,researchers have proposed a number of solutions around the selection and optimization of CAR-T targets,the structural design of CAR and the breakage of tumor microenvironmental immunosuppression,and some candidate products have been in clinical trial study.This paper reviews the recent advances in research on the application of CAR-T therapy to solid tumors.