Research Status and Outlook of PD-1/PD-L1 Inhibitors for Cancer Therapy

Drug Des Devel Ther. 2020 Sep 8:14:3625-3649. doi: 10.2147/DDDT.S267433. eCollection 2020.

Abstract

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.

Keywords: PD-1; PD-L1; adverse events; clinical trials; immune checkpoint inhibitors; monoclonal antibody.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / metabolism
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / metabolism

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor

Grants and funding

This work was supported by the Natural Science Foundation of China (No. 81773816).