Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells - Archive ouverte HAL Access content directly
Journal Articles Cell Year : 2018

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

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

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.

Dates and versions

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

Licence

Attribution - CC BY 4.0

Identifiers

Cite

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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