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

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

Cell reports. Medicine (2022-10-20)
Olivier Demaria, Laurent Gauthier, Marie Vetizou, Audrey Blanchard Alvarez, Constance Vagne, Guillaume Habif, Luciana Batista, William Baron, Nourhène Belaïd, Mathilde Girard-Madoux, Cedric Cesari, Melody Caratini, Frédéric Bosco, Olivier Benac, Julie Lopez, Aurore Fenis, Justine Galluso, Sylvia Trichard, Barbara Carrette, Florent Carrette, Aurélie Maguer, Solène Jaubert, Audrey Sansaloni, Robin Letay-Drouet, Camille Kosthowa, Naouel Lovera, Arnaud Dujardin, Fabien Chanuc, Mélanie Le Van, Sivan Bokobza, Nicolas Jarmuzynski, Camille Fos, Nicolas Gourdin, Romain Remark, Eric Lechevallier, Nicolas Fakhry, Sébastien Salas, Jean-Laurent Deville, Roger Le Grand, Cécile Bonnafous, Lukas Vollmy, Agnès Represa, Sabrina Carpentier, Benjamin Rossi, Ariane Morel, Stéphanie Cornen, Ivan Perrot, Yannis Morel, Eric Vivier
PMID36260981
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.

MATERIALS
Product Number
Brand
Product Description
11284932001
Roche
DNase I, from bovine pancreas
A9418
Sigma-Aldrich
Bovine Serum Albumin, lyophilized powder, BioReagent, suitable for cell culture
PRCYTOMAG-40K
Millipore
MILLIPLEX® Non-Human Primate Cytokine Magnetic Bead Panel - Immunology Multiplex Assay, Simultaneously analyze multiple cytokine and chemokine biomarkers with Bead-Based Multiplex Assays using the Luminex technology, in mouse serum, plasma and cell culture samples.