Center for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China.
Drug Des Devel Ther. 2020 Sep 8;14:3625-3649. doi: 10.2147/DDDT.S267433. eCollection 2020.
PD-1/PD-L1 inhibitors are a group of immune checkpoint inhibitors as front-line treatment of multiple types of cancer. However, the serious immune-related adverse reactions limited the clinical application of PD-1/PD-L1 monoclonal antibodies, despite the promising curative effects. Therefore, it is urgent to develop novel inhibitors, such as small molecules, peptides or macrocycles, targeting the PD-1/PD-L1 axis to meet the increasing clinical demands. Our review discussed the mechanism of action of PD-1/PD-L1 inhibitors and presented clinical trials of currently approved PD-1/PD-L1 targeted drugs and the incidence of related adverse reactions, helping clinicians pay more attention to them, better formulate their intervention and resolution strategies. At last, some new inhibitors whose patent have been published are listed, which provide development ideas and judgment basis for the efficacy and safety of novel PD-1/PD-L1 inhibitors.
PD-1/PD-L1 抑制剂是一组免疫检查点抑制剂,作为多种癌症的一线治疗药物。然而,严重的免疫相关不良反应限制了 PD-1/PD-L1 单克隆抗体的临床应用,尽管其疗效有很大的潜力。因此,迫切需要开发针对 PD-1/PD-L1 轴的新型抑制剂,如小分子、肽或大环化合物,以满足不断增长的临床需求。本综述讨论了 PD-1/PD-L1 抑制剂的作用机制,并介绍了目前已批准的 PD-1/PD-L1 靶向药物的临床试验和相关不良反应的发生率,有助于临床医生更多地关注这些药物,更好地制定干预和解决策略。最后,列出了一些已公布专利的新型抑制剂,为新型 PD-1/PD-L1 抑制剂的疗效和安全性提供了开发思路和判断依据。