[PDF][PDF] Anti-NKG2A mAb is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells

P André, C Denis, C Soulas, C Bourbon-Caillet… - Cell, 2018 - cell.com
P André, C Denis, C Soulas, C Bourbon-Caillet, J Lopez, T Arnoux, M Bléry, C Bonnafous…
Cell, 2018cell.com
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 …
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.
cell.com