嵌合抗原受体T细胞介绍及抗肿瘤临床应用

过继性细胞免疫治疗（adoptive cellular immunotherapy,ACI）是目前较为有效的恶性肿瘤的治疗方法之一。随着技术的日趋成熟，已在多种实体瘤和血液肿瘤的t临床治疗中取得较好疗效。其中，嵌合抗原受体（chimeric antigen receptor,CAR）T细胞技术是近年来发展非常迅速的一种细胞治疗技术。通过基因改造技术，效应T细胞的靶向性、杀伤活性和持久性均较常规应用的免疫细胞高，并可克服肿瘤局部免疫抑制微环境和打破宿主免疫耐受状态。目前，CAR的信号域已从第一代的单一信号分子发展为包含CD28、4—1BB等共刺激分子的多信号结构域（第二、三代），临床应用广泛。但是，该技术也存在脱靶效应、插入突变等临床应用风险。该文将就CAR—T细胞技术在恶性肿瘤免疫治疗中的应用及可能存在的问题作一综述。

Introduction of Chimeric Antigen Receptor-engineered T Cells and the Clinical Use for Anticancer

Adoptive cellular immunotherapy （ACI） is one of the most effective comprehensive anticancer therapies. It has achieved expectable curative effect on different solid tumors and hematological malignancies suggested by recent data and striking clinical responses. As an ACI, chimeric antigen receptor （CAR）-engineered T cell therapy has been rapidly developed in recent years. By the use of genetic modification techniques, effector T cells have better properties with regard to targeting, killing activity and durability than immunocytes of conventional ap- plication. CAR-T cells can overcome the local immunosuppressive tumor microenvironment and break the immune tolerance in host. At present, the signal domain of CAR has been developed from the single to multiple structure containing costimulatory molecules such as CD28 and 4-1BB, and has been widely used in clinic. However, there are potential risks on account of the off-target effect, insertion mutation, etc. In this paper, applications and prob- lems of CAR-T cells in cancer immunotherapy are reviewed for clinical guidance.