生物学杂志

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双特异性单链抗体BiTE的研究进展

  

  1. 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
  • 出版日期:2018-08-18 发布日期:2018-08-18
  • 通讯作者: 施海峰,教授,博士生导师,研究方向为细胞代谢与分子营养,E-mail:shihf@ujs.edu.cn
  • 作者简介:周 冲,硕士研究生,研究方向为细胞生物学,E-mail:zhouchong1992@163.com
  • 基金资助:
    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)

Research progress in the bispecific single chain antibody of BiTE

  1. 1. Institute of Life Sciences, Jiangsu University, Zhenjiang 212013; 2. Engineering Technology Research Center of Research and Development of Traditional Chinese Medicine, College of Biological and Pharmaceutical Engineering, West Anhui University, Lu′an 237012; 3. Department  of Hematology, Shenzhen Nanshan Hospital, Shenzhen 518052, China
  • Online:2018-08-18 Published:2018-08-18

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。

关键词: 双特异性单链抗体, BiTE, 免疫治疗

Abstract: 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.

Key words: bispecific single chain antibody, BiTE, immunotherapy