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Ref Type Journal Article
PMID (30503213)
Authors André P, Denis C, Soulas C, Bourbon-Caillet C, Lopez J, Arnoux T, Bléry M, Bonnafous C, Gauthier L, Morel A, Rossi B, Remark R, Breso V, Bonnet E, Habif G, Guia S, Lalanne AI, Hoffmann C, Lantz O, Fayette J, Boyer-Chammard A, Zerbib R, Dodion P, Ghadially H, Jure-Kunkel M, Morel Y, Herbst R, Narni-Mancinelli E, Cohen RB, Vivier E
Title Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells.
URL
Abstract Text Checkpoint inhibitors have revolutionized cancer treatment. However, only a minority of patients respond to these immunotherapies. Here, we report that blocking the inhibitory NKG2A receptor enhances tumor immunity by promoting both natural killer (NK) and CD8+ T cell effector functions in mice and humans. Monalizumab, a humanized anti-NKG2A antibody, enhanced NK cell activity against various tumor cells and rescued CD8+ T cell function in combination with PD-x axis blockade. Monalizumab also stimulated NK cell activity against antibody-coated target cells. Interim results of a phase II trial of monalizumab plus cetuximab in previously treated squamous cell carcinoma of the head and neck showed a 31% objective response rate. Most common adverse events were fatigue (17%), pyrexia (13%), and headache (10%). NKG2A targeting with monalizumab is thus a novel checkpoint inhibitory mechanism promoting anti-tumor immunity by enhancing the activity of both T and NK cells, which may complement first-generation immunotherapies against cancer.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Monalizumab Monalizumab 0 2
Drug Name Trade Name Synonyms Drug Classes Drug Description
Monalizumab NN-8765|IPH-2201|IPH 2201|IPH2201 NKG2A Antibody 3 Monalizumab (IPH2201) is a humanized monoclonal antibody against NKG2A that blocks NKG2A ligand binding, which in turn induces cell-mediated immune response against cancer cells (PMID: 30503213, PMID: 31623687, PMID: 31308062).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References