PD-1/PD-L1抗体阻断药物的研究进展与临床应用

研究发现在生理状况下PD-1与PD-L1相互识别能产生负向信号,该信号通路一旦被激活后,可诱导抗原特异性效应T细胞凋亡,该生理效应可防止过度免疫反应带来的附加损伤,因此该信号通路又被形象的称为"免疫刹车".如果利用特异性阻断剂阻断PD-1/PD-L1信号通路,便可以恢复免疫细胞的杀伤抑制功能.截止至2019年12月,全球已有7种PD-1阻断药物和3种PD-L1阻断药物批准上市,均属于大分子抗体类药物,其中的4种PD-1单抗由我国自主研发,目前中国大陆批准上市的PD-1/PD-L1阻断药物有8种.这些单抗药物在多种肿瘤的临床治疗中产生较好的疗效,并且部分患者得到完全缓解,具有良好的应用前景.从其生物学背景出发,按药物分类综述了近年来PD-1/PD-L1信号通路抑制剂在临床治疗中的应用和表现,讨论了目前此类药物在临床使用中存在的问题以及应对策略.

Research progress and clinical application of PD-1/PD-L1 antibody-blocking drugs

Many studies have found that the mutual recognition of PD-1 and PD-L1 could produce negative signals under physiological conditions. Once the signaling pathway was activated, and the signaling pathway could induce the apoptosis of antigen-specific effect T cells. Then the physiological effect could prevent additional damages which caused by excessive immune response. Therefore, the signaling pathway is named as the "immune brake". If the PD-1/PD-L1 signaling pathway was blocked by a specific blocker, the killing inhibitory function of immune cells would be restored. Up to the December of 2019, seven PD-1 blocking drugs and three PD-L1 blocking drugs have been approved for marketing worldwide, all of which belonging to macromolecular antibody drugs. Among them, four PD-1 monoclonal antibodies were independently developed in China. Currently, eight PD-1/PD-L1 blocking drugs have been approved for marketing in mainland China. These monoclonal antibodies have produced good efficacy in the clinical treatment of different tumors. A few patients have achieved complete remission, forecasting a good application prospect for these antibodies. Based on its biological background, we reviewed the application and performance of PD-1/PD-L1 signaling pathway inhibitors in clinical treatment in recent years according to drug classification, and discussed the existing problems in clinical use of such drugs and corresponding strategies.