Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells
2018; Cell Press; Volume: 175; Issue: 7 Linguagem: Inglês
10.1016/j.cell.2018.10.014
ISSN1097-4172
AutoresPascale André, Caroline Denis, Caroline Soulas, Clarisse Bourbon-Caillet, Julie Lopez, Thomas Arnoux, Mathieu Bléry, Cécile Bonnafous, Laurent Gauthier, Ariane Morel, Benjamín Rossi, Romain Remark, Violette Breso, Elodie Bonnet, Guillaume Habif, Sophie Guia, Ana I. Lalanne, Caroline Hoffmann, Olivier Lantz, Jérôme Fayette, Agnès Boyer-Chammard, Robert Zerbib, P. Dodion, Hormas Ghadially, Maria Jure‐Kunkel, Yannis Morel, Ronald Herbst, Émilie Narni-Mancinelli, Roger B. Cohen, Éric Vivier,
Tópico(s)Cancer Immunotherapy and Biomarkers
ResumoHighlights•Blocking NKG2A unleashes both T and NK cell effector functions•Combined blocking of the NKG2A and the PD-1 axis promotes anti-tumor immunity•Blocking NKG2A and triggering CD16 illustrates the efficacy of dual checkpoint therapySummaryCheckpoint 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.Graphical abstract
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