Title: A tetraspecific engager armed with a non-alpha IL-2 variant harnesses natural killer cells against B cell non-Hodgkin lymphoma
Authors: Olivier Demaria 1 , Guillaume Habif 1 , Marie Vetizou 1 , Laurent Gauthier 1 , Romain Remark 1 , Laura Chiossone 1 , Constance Vagne 1 , Lucas Rebuffet 2 , Rachel Courtois 1 , Caroline Denis 1 , François Le Floch 1 , Marianna Muller 1 , Mathilde Girard-Madoux 1 , Séverine Augier 1 , Julie Lopez 1 , Barbara Carrette 1 , Aurélie Maguer 1 , Jean-Baptiste Vallier 1 , Gwendoline Grondin 1 , William Baron 1 , Justine Galluso 1 , Nadia Yessaad 1 , Marilyn Giordano 1 , Léa Simon 1 , Fabien Chanuc 1 , Audrey Blanchard Alvarez 1 , Ivan Perrot 1 , Cécile Bonnafous 1 , Agnès Represa 1 , Benjamin Rossi 1 , Ariane Morel 1 , Yannis Morel 1 , Carine Paturel 1 , Eric Vivier 1 2 3 4 5
1 Innate Pharma Research Laboratories, Innate Pharma, Marseille, France. 2 Aix Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France. 3 APHM, Hôpital de la Timone, Marseille-Immunopôle Profiling Platform, Marseille, France. 4 Paris-Saclay Cancer Cluster, Le Kremlin-Bicêtre, France. 5 Université Paris-Saclay, Gustave Roussy, INSERM, Prédicteurs moléculaires et nouvelles cibles en oncologie, 94800, Villejuif, France.
DOI: 10.1126/sciimmunol.adp3720
Summary: NK cells offer a promising alternative to T cell therapies in cancer. We evaluated IPH6501, a clinical-stage, tetraspecific NK cell engager (NKCE) armed with a non-alpha IL-2 variant (IL-2v), which targets CD20 and was developed for treating B cell non-Hodgkin lymphoma (B-NHL). CD20-NKCE-IL2v boosts NK cell proliferation and cytotoxicity, showing activity against a range of B-NHL cell lines, including those with low CD20 density. Whereas it presented reduced toxicities compared with those commonly associated with T cell therapies, CD20-NKCE-IL2v showed greater killing efficacy over a T cell engager targeting CD20 in in vitro preclinical models. CD20-NKCE-IL2v also increased the cell surface expression of NK cell-activating receptors, leading to activity against CD20-negative tumor cells. In vivo studies in nonhuman primates and tumor mouse models further validated its efficacy and revealed that CD20-NKCE-IL2v induces peripheral NK cell homing at the tumor site. CD20-NKCE-IL2v emerges as a potential alternative in the treatment landscape of B-NHL.
This github project contains the instructions and material to reproduce the analyses reported in the article (and more). Source code (scripts and dockerfiles) are available in the github repository.