Monalizumab: inhibiting the novel immune checkpoint NKG2A

J Immunother Cancer. 2019 Oct 17;7(1):263. doi: 10.1186/s40425-019-0761-3.

Abstract

The implementation of immune checkpoint inhibitors to the oncology clinic signified a new era in cancer treatment. After the first indication of melanoma, an increasing list of additional cancer types are now treated with immune system targeting antibodies to PD-1, PD-L1 and CTLA-4, alleviating inhibition signals on T cells. Recently, we published proof-of-concept results on a novel checkpoint inhibitor, NKG2A. This receptor is expressed on cytotoxic lymphocytes, including NK cells and subsets of activated CD8+ T cells. Blocking antibodies to NKG2A unleashed the reactivity of these effector cells resulting in tumor control in multiple mouse models and an early clinical trial. Monalizumab is inhibiting this checkpoint in human beings and future clinical trials will have to reveal its potency in combination with other cancer treatment options.

Keywords: CD8 T cells; Cancer immunotherapy; HLA-E/Qa-1; Inhibitory immune receptor; NK cells; NKG2A.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / pharmacology*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Disease Models, Animal
  • HLA-E Antigens
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily C / antagonists & inhibitors*
  • NK Cell Lectin-Like Receptor Subfamily C / immunology
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Histocompatibility Antigens Class I
  • KLRC1 protein, human
  • Klrc1 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily C
  • Q surface antigens
  • monalizumab