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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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https://hal-amu.archives-ouvertes.fr/hal-02023782
Contributor : Carine Dou Goarin <>
Submitted on : Monday, February 18, 2019 - 4:36:35 PM
Last modification on : Tuesday, July 21, 2020 - 3:58:30 AM

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Pascale Andre, Caroline Denis, Caroline Soulas, Clarisse Bourbon-Caillet, Julie Lopez, et al.. Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells. Cell, Elsevier, 2018, 175 (7), pp.1731-1743.e13. ⟨10.1016/j.cell.2018.10.014⟩. ⟨hal-02023782⟩

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