Immune Checkpoint Inhibitors: Basics and Challenges

Curr Med Chem. 2019;26(17):3009-3025. doi: 10.2174/0929867324666170804143706.

Abstract

Cancer is one of the most deadly diseases in the modern world. The last decade has witnessed dramatic advances in cancer treatment through immunotherapy. One extremely promising means to achieve anti-cancer immunity is to block the immune checkpoint pathways - mechanisms adopted by cancer cells to disguise themselves as regular components of the human body. Many review articles have described a variety of agents that are currently under extensive clinical evaluation. However, while checkpoint blockade is universally effective against a broad spectrum of cancer types and is mostly unrestricted by the mutation status of certain genes, only a minority of patients achieve a complete response. In this review, we summarize the basic principles of immune checkpoint inhibitors in both antibody and smallmolecule forms and also discuss potential mechanisms of resistance, which may shed light on further investigation to achieve higher clinical efficacy for these inhibitors.

Keywords: CTLA-4; Immunotherapy; PD-1; T cells; checkpoint blockade; resistance..

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Cell Cycle Checkpoints / drug effects*
  • Humans
  • Immunotherapy*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Neoplasms / therapy*

Substances

  • Antineoplastic Agents