抗体—超抗原融合蛋白及其应用的研究进展

Advance in Antibody-Superantigen Fusion Protein and Application

超抗原(Superantigen,SAg)是一类具有多种免疫活性的蛋白分子,在一定条件下能比普通抗原十至数千倍激活T细胞和抗原呈递细胞。超抗原能引导T细胞产生细胞毒作用(SDCC)和诱导产生一些细胞因子来杀伤肿瘤细胞。然而单用SAg效果差,毒副作用强,其作用受到限制。研究表明使用肿瘤特异性的单抗Fab-SAg融合蛋白,能比单用SAg取得更稳定、更明显的效果。该融合蛋白对肿瘤部位的靶向性强、亲和力高,并能很好地减少系统的免疫原性。另外发现使用突变的Fab-SAg融合蛋白,能进一步增加动物的耐受性、降低毒副作用。目前已有多个用单抗Fab-SAg融合蛋白药物进入临床研究,该药物将会为治疗人类恶性肿瘤带来希望。

Superantigen（SAg） is a kind of protein having many immunological activities. It can kill the tumor cells by inducing the SDCC effect of T-cell and secretion of cytokine such as IFN-γ,TNFα. However the therapeutic effects of SAg are very low, and can bring much toxicity. Recent research shows that the specific antibody fragment Fab and SAg fusion protein has a very high affinity to tumor cells. The most important is that its immunogenic activity is much lower than non-fusion protein. In addition, the studies also show if the SAg is mutated before fusion, the mutated fusion protein has less toxicity and much more maximum tolerated dose（MTD） than ever. The research shows that Fab-SAg fusion protein has a very promising prospect in cancer therapy in future.