Monalizumab: inhibiting the novel immune checkpoint NKG2A

Thorbald van Hall; Pascale André; Amir Horowitz; Dan Fu Ruan; Linda Borst; Robert Zerbib; Emilie Narni-Mancinelli; Sjoerd H van der Burg; Eric Vivier

doi:10.1186/s40425-019-0761-3

Monalizumab: inhibiting the novel immune checkpoint NKG2A

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

Authors

Affiliations

¹ Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, 2333, ZA, Leiden, the Netherlands. [email protected].
² Innate Pharma Research Labs, Innate Pharma, Marseille, France.
³ Department of Oncological Sciences, Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
⁴ Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, 2333, ZA, Leiden, the Netherlands.
⁵ Aix Marseille Université, INSERM, CNRS, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
⁶ Innate Pharma Research Labs, Innate Pharma, Marseille, France. [email protected].
⁷ Aix Marseille Université, INSERM, CNRS, Centre d'Immunologie de Marseille-Luminy, Marseille, France. [email protected].
⁸ Service d'Immunologie, Marseille Immunopole, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France. [email protected].

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