Journal Articles Cell Reports Medicine Year : 2022

Antitumor immunity induced by antibody-based natural killer cell engager therapeutics armed with not-alpha IL-2 variant

Olivier Demaria
Constance Vagne
  • Function : Author
Guillaume Habif
  • Function : Author
Luciana Batista
  • Function : Author
Nourhène Belaïd
  • Function : Author
Cedric Cesari
  • Function : Author
Melody Caratini
  • Function : Author
Frédéric Bosco
  • Function : Author
Olivier Benac
  • Function : Author
Sylvia Trichard
  • Function : Author
Barbara Carrette
  • Function : Author
Florent Carrette
  • Function : Author
Aurélie Maguer
  • Function : Author
Solène Jaubert
  • Function : Author
Audrey Sansaloni
  • Function : Author
Robin Letay-Drouet
  • Function : Author
Camille Kosthowa
  • Function : Author
Naouel Lovera
  • Function : Author
Arnaud Dujardin
  • Function : Author
Fabien Chanuc
  • Function : Author
Mélanie Le Van
  • Function : Author
Sivan Bokobza
  • Function : Author
Nicolas Jarmuzynski
  • Function : Author
Camille Fos
  • Function : Author
Nicolas Gourdin
  • Function : Author
Romain Remark
  • Function : Author
Eric Lechevallier
  • Function : Author
Nicolas Fakhry
  • Function : Author
Jean-Laurent Deville
  • Function : Author
Roger Le Grand
  • Function : Author
Cécile Bonnafous
  • Function : Author
Lukas Vollmy
  • Function : Author
Agnès Represa
  • Function : Author
Sabrina Carpentier
  • Function : Author
Benjamin Rossi
  • Function : Author
Ariane Morel
  • Function : Author
Stéphanie Cornen
  • Function : Author
Ivan Perrot
  • Function : Author
Yannis Morel
  • Function : Author

Abstract

Harnessing innate immunity is emerging as a promising therapeutic approach in cancer. We report here the design of tetraspecific molecules engaging natural killer (NK) cell-activating receptors NKp46 and CD16a, the β-chain of the interleukin-2 receptor (IL-2R), and a tumor-associated antigen (TAA). In vitro, these tetraspecific antibody-based natural killer cell engager therapeutics (ANKETs) induce a preferential activation and proliferation of NK cells, and the binding to the targeted TAA triggers NK cell cytotoxicity and cytokine and chemokine production. In vivo, tetraspecific ANKETs induce NK cell proliferation and their accumulation at the tumor bed, as well as the control of local and disseminated tumors. Treatment of non-human primates with CD20-directed tetraspecific ANKET leads to CD20+ circulating B cell depletion, with minimal systemic cytokine release and no sign of toxicity. Tetraspecific ANKETs, thus, constitute a technological platform for harnessing NK cells as next-generation cancer immunotherapies.

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Cancer
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hal-03925668 , version 1 (09-11-2023)

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Olivier Demaria, Laurent Gauthier, Marie Vetizou, Audrey Blanchard Alvarez, Constance Vagne, et al.. Antitumor immunity induced by antibody-based natural killer cell engager therapeutics armed with not-alpha IL-2 variant. Cell Reports Medicine, 2022, 3 (10), pp.100783. ⟨10.1016/j.xcrm.2022.100783⟩. ⟨hal-03925668⟩
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