Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells
By P. André, C. Denis, C. Soulas, Clarisse Bourbon-Caillet, Julie Lopez, T. Arnoux, M. Bléry, C. Bonnafous, L. Gauthier, Ariane Morel and 20 more. Cell, 2018
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Summary 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.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/64469f9a485b014d8e6b4ec2acc60fe89cde0bde
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In Oncology
Citations in the corpus
- The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC) (2019, background): “The safety of the combination was acceptable with no potentiation of cetuximab adverse events [127, 163].”