基于嵌合抗原受体修饰T细胞的肿瘤免疫治疗新策略  

New strategy of tumor immunotherapy based on chimeric antigen receptor engineered T cells

作　　者：王艺[1] 赵颖颖[1] 韩双印[1] 

机构地区：[1]郑州大学人民医院中心实验室,河南郑州450003

出　　处：《中国肿瘤生物治疗杂志》2013年第4期383-390,共8页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金资助项目(No.81172415;No.81241077);河南省重点科技攻关项目资助(No.102102310065)~~

摘　　要：嵌合抗原受体(chimeric antigen receptor,CAR)修饰T细胞是近年来迅速发展的肿瘤过继免疫治疗新手段,其独特的作用机制和诱人的应用前景为肿瘤生物治疗开辟了一个崭新的舞台。CAR将识别肿瘤相关抗原的单链抗体和T细胞的活化基序相结合,通过基因转导赋予T细胞肿瘤靶向性、更强的杀伤活性和持久的生命力。自1989年Eshhar等首次提出CAR以来,CAR已从第一代发展至含有共刺激分子的第二、三代,CAR的Ⅰ/Ⅱ期临床试验在白血病、淋巴瘤、黑素瘤等恶性肿瘤中取得了可喜的成果,但是也面临脱靶效应、细胞因子风暴、移植物抗宿主病等潜在的安全性问题,未来研究将集中于设计更安全的第四代CAR、甄选具备最佳治疗潜质的T细胞亚群、优化临床治疗方案、完善临床前试验模型等方面。相信随着免疫学、基因治疗和细胞工程等领域不断取得新突破,CAR从实验室向临床转化的障碍将会逐一扫除,CAR有望成为主流的肿瘤治疗方法。Chimeric antigen receptor （CAR） -engineered T cell is a newly developed strategy of adoptive immunothera- py. Its unique theoretical superiority and attractive application prospects open up a promising arena for anticancer therapy. CAR combines single chain variable fragment （scFv） antibody recognizing tumor-associated antigen with T cell activation motif, whieh endows T cells with tumor-orientated targeting ability, stronger killing activity, and prolonged survival by ge- netic modification. Since first proposed by Dr. Eshhar in 1989, CAR has been developed from the first generation to the second and the third generations containing costimulatory molecular. The clinical trials in leukemia, lymphoma, and mela- noma have ohtained exciting results. However, the off-target effect, cytokine strom, and graft-versus-host disease are po- tential challenges for clinical use. Future research will focus on designing safer CAR of the fourth generation, selecting good therapeutic T cell subsets, optimizing clinical scheme of administration, and improving pre-clinical models. It is be- lieved that the obstacles from beneh to clinic will be cleared and that CAR will become one of the main cancer therapies with breakthroughs in immunology, gene therapy and cell engineering.

关 键 词：嵌合抗原受体 过继免疫治疗 肿瘤靶向治疗 

分 类 号：R730.51[医药卫生—肿瘤] R392.11[医药卫生—临床医学]