2. Academic Validation
  3. Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells

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

  • Cell. 2018 Dec 13;175(7):1731-1743.e13. doi: 10.1016/j.cell.2018.10.014.
Pascale André 1,  Caroline Denis 2,  Caroline Soulas 2,  Clarisse Bourbon-Caillet 2,  Julie Lopez 2,  Thomas Arnoux 2,  Mathieu Bléry 2,  Cécile Bonnafous 2,  Laurent Gauthier 2,  Ariane Morel 2,  Benjamin Rossi 2,  Romain Remark 2,  Violette Breso 2,  Elodie Bonnet 2,  Guillaume Habif 2,  Sophie Guia 3,  Ana Ines Lalanne 4,  Caroline Hoffmann 5,  Olivier Lantz 4,  Jérôme Fayette 6,  Agnès Boyer-Chammard 2,  Robert Zerbib 2,  Pierre Dodion 2,  Hormas Ghadially 7,  Maria Jure-Kunkel 8,  Yannis Morel 2,  Ronald Herbst 8,  Emilie Narni-Mancinelli 3,  Roger B Cohen 9,  Eric Vivier 10
Affiliations

Affiliations

  • 1 Innate Pharma, 117 Avenue de Luminy, 13009 Marseille, France. Electronic address: pascale.andre@innate-pharma.fr.
  • 2 Innate Pharma, 117 Avenue de Luminy, 13009 Marseille, France.
  • 3 Aix Marseille Université, INSERM, CNRS, Centre d'Immunologie de Marseille-Luminy, 13009 Marseille, France.
  • 4 Unité INSERM U932, Immunité et Cancer, Institut Curie, 75248 Paris Cedex 5, France.
  • 5 Unité INSERM U932, Immunité et Cancer, Institut Curie, 75248 Paris Cedex 5, France; Service ORL et Chirurgie cervico-faciale, Institut Curie, 75248 Paris Cedex 5, France.
  • 6 Centre Léon Bérard, 69008 Lyon, France.
  • 7 MedImmune, Ltd., Aaron Klug Building, Granta Park, Cambridge, CB21 6GH, UK.
  • 8 MedImmune, LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
  • 9 Abramson Cancer Center, 3400 Civic Center Boulevard West Pavilion, Philadelphia, PA, USA.
  • 10 Innate Pharma, 117 Avenue de Luminy, 13009 Marseille, France; Aix Marseille Université, INSERM, CNRS, Centre d'Immunologie de Marseille-Luminy, 13009 Marseille, France; Service d'Immunologie, Marseille Immunopole, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, 13005 Marseille, France. Electronic address: vivier@ciml.univ-mrs.fr.
PMID: 30503213 DOI: 10.1016/j.cell.2018.10.014
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.

Keywords

CD8(+) T cells; cancer immunotherapy; immunce checkpoint inhibitor; inhibitory receptors; lymphocytes; natural killer cells; therapeutic monoclonal antibodies.

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