Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells

Abstract

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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Affiliated Institutions

• Centre National de la Recherche Scientifique FR
• Hôpital de la Timone FR
• Inserm FR
• Assistance Publique Hôpitaux de Marseille FR
• Institut Curie FR
• Abramson Cancer Center
• Innate Pharma (France) FR
• Aix-Marseille Université FR
• Centre Léon Bérard FR
• Centre d’Immunologie de Marseille-Luminy FR
• Immunité et Cancer FR

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