双特异性单链抗体BiTE的研究进展

Research progress in the bispecific single chain antibody of BiTE

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.