双特异性单链抗体BiTE的研究进展  

Research progress in the bispecific single chain antibody of BiTE

作　　者：周冲[1] 于峰[1] 韩邦兴 周阳[1] 刘黎琼[3] 施海峰[1] ZHOU Chong;YU Feng;HAN Bang-xing;ZHOU Yang;LIU Li-qiong;SHI Hai-feng(Institute of Life Sciences,Jiangsu University,Zhenjiang 212013;Engineering Technology- Research Center of Research and Development of Traditional Chinese Medicine,College of Biological and Pharmaceutical Engineering,West Anhui University,Lu＇an 237012;Department of Hematology,Shenzhen Nanshan Hospital,Shenzhen 518052,China)

机构地区：[1]江苏大学生命科学研究院,镇江212013 [2]皖西学院生物与制药工程学院中药研究与开发工程技术研究中心,六安237012 [3]深圳市南山区人民医院血液科,深圳518052

出　　处：《生物学杂志》2018年第4期76-80,共5页Journal of Biology

基　　金：国家自然科学基金(31271272);广东省自然科学基金项目(2016A030313032);深圳市科技研发资金基础研究(JCYJ20160429182558793);深圳市南山区卫生计划项目(No.2015001)

摘　　要：癌症是严重威胁人类生存的重大疾病。BiTE(bispecific T-cell engager)所代表的一类具有显著抗肿瘤效应的双特异抗体,能够靶向性激活自身T细胞杀伤肿瘤细胞。BiTE由两个单链可变片段(scFv)组成,通过柔性融合接头串联连接。一个scFv识别T细胞表面蛋白CD3ε,而另一个scFv识别特异性肿瘤细胞表面抗原。BiTE的这种结构和特异性结合蛋白能力允许它将T细胞物理性地桥接肿瘤细胞而形成T细胞-BiTE-肿瘤细胞复合物,诱导免疫突触形成,刺激T细胞活化,产生杀伤肿瘤的细胞因子。近年来,BiTE在抗肿瘤研究中取得了显著进展,在临床上取得了理想的治疗效果。因此,对BiTE的结构、作用机制、临床应用以及创新性运用进行阐述。Cancer is the severest disease threatening human health. BiTE （bispecific T cell engager）represents a subclass of bispecific antibodies which have significant anti-tumor effects, activating the T cells of patients to kill cancer cells. It consists of two single chain variable fragments （scFvs）connected in tandem by a soft fusion linker. One of the scFv recognizes CD3ε on the surface of T cell, the other one recognizes tumor surface antigen. This structure and the specificity allow BiTE physically bridging T cell and tumor cell to form a T cell-BiTE-tumor cell complex, inducing formation of synapse, stimulating activation of T cell and production of tumor killing cytokines. In recent years, there has been a big progress in the BiTE anti-tumor research and promising effects in clinical studies. Therefore, in this paper, we review the biostructure, anti-tumor mechanism, clinical application and innovative usage of BiTE.

关 键 词：双特异性单链抗体 BITE 免疫治疗 

分 类 号：Q78[生物学—分子生物学]