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Cell. 2019 Jun 13;177(7):1701-1713.e16. doi: 10.1016/j.cell.2019.04.041. Epub 2019 May 30.

Multifunctional Natural Killer Cell Engagers Targeting NKp46 Trigger Protective Tumor Immunity.

Author information

1
Innate Pharma, Marseille, France. Electronic address: laurent.gauthier@innate-pharma.fr.
2
Innate Pharma, Marseille, France.
3
Aix Marseille Université, CNRS, Architecture et Fonction des Macromolécules Biologiques, Marseille, France.
4
MI-mAbs, Aix Marseille Université, Marseille, France.
5
Aix Marseille Université, INSERM, CNRS, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
6
Innate Pharma, Marseille, France; Aix Marseille Université, INSERM, CNRS, Centre d'Immunologie de Marseille-Luminy, Marseille, France; Service d'Immunologie, Marseille Immunopole, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France. Electronic address: vivier@ciml.univ-mrs.fr.

Abstract

Over the last decade, various new therapies have been developed to promote anti-tumor immunity. Despite interesting clinical results in hematological malignancies, the development of bispecific killer-cell-engager antibody formats directed against tumor cells and stimulating anti-tumor T cell immunity has proved challenging, mostly due to toxicity problems. We report here the generation of trifunctional natural killer (NK) cell engagers (NKCEs), targeting two activating receptors, NKp46 and CD16, on NK cells and a tumor antigen on cancer cells. Trifunctional NKCEs were more potent in vitro than clinical therapeutic antibodies targeting the same tumor antigen. They had similar in vivo pharmacokinetics to full IgG antibodies and no off-target effects and efficiently controlled tumor growth in mouse models of solid and invasive tumors. Trifunctional NKCEs thus constitute a new generation of molecules for fighting cancer. VIDEO ABSTRACT.

KEYWORDS:

cancer immunotherapy; monoclonal antibodies; natural killer cells

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PMID:
31155232
DOI:
10.1016/j.cell.2019.04.041

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