Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Cell Année : 2018

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

Pascale Andre
  • Fonction : Auteur
Caroline Denis
  • Fonction : Auteur
Caroline Soulas
  • Fonction : Auteur
Julie Lopez
  • Fonction : Auteur
Thomas Arnoux
  • Fonction : Auteur
Mathieu Blery
  • Fonction : Auteur
Cécile Bonnafous
  • Fonction : Auteur
Laurent Gauthier
  • Fonction : Auteur
Ariane Morel
  • Fonction : Auteur
Benjamin Rossi
Romain Remark
  • Fonction : Auteur
Violette Breso
  • Fonction : Auteur
Elodie Bonnet
  • Fonction : Auteur
Guillaume Habif
  • Fonction : Auteur
Sophie Guia
Ana Inés Lalanne
  • Fonction : Auteur
  • PersonId : 842181
Olivier Lantz
Robert Zerbib
  • Fonction : Auteur
Pierre Dodion
  • Fonction : Auteur
Yannis Morel
  • Fonction : Auteur
Ronald Herbst
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-02023782 , version 1 (18-02-2019)

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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, 2018, 175 (7), pp.1731-1743.e13. ⟨10.1016/j.cell.2018.10.014⟩. ⟨hal-02023782⟩
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