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

Monalizumab: Inhibiting the Novel Immune Checkpoint NKG2A

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Free PMC article
Review

Monalizumab: Inhibiting the Novel Immune Checkpoint NKG2A

Thorbald van Hall et al. J Immunother Cancer. .
Free PMC article

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.

Conflict of interest statement

P.A., R.Z. and E. V are employees of Innate-Pharma. The other authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
Schematic model describing the effects of HLA-E expression in the tumor microenvironment (TME) and the use of monalizumab to abrogate inhibition of NKG2A-expressing cells. a HLA-E expression on tumors mediates inhibition of NKG2A-expressing NK cells and CD8+ T cells and leads to tumor escape. b Use of NKG2A-blocking antibody monalizumab unleashes inhibition of NKG2A-expressing cells and promotes activation of NK cells and CD8+ T cells

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