Development of ICT01, a first-in-class, anti-BTN3A antibody for activating Vγ9Vδ2 T cell–mediated antitumor immune response
Aude De Gassart, Kieu-Suong Le, Patrick Brune, Sophie Agaugué, Jennifer S. Sims, Armelle Goubard, Rémy Castellano, Noémie Joalland, Emmanuel Scotet, Yves Collette, Emmanuel Valentin, Clément Ghigo, Christine L. Pasero, Magali Colazet, Jaime Guillén, Carla E. Cano, Aurélien Marabelle, Johann S. de Bono, René Hoet, Alemseged Truneh, Daniel Olive, Paul Frohna
Abstract
(NSG) mice adoptively transferred with human Vγ9Vδ2 T cells. In single- and multiple-dose safety studies in cynomolgus macaques that received up to 100 mg/kg once weekly, ICT01 was well tolerated. With respect to pharmacodynamic endpoints, ICT01 selectively activated Vγ9Vδ2 T cells without affecting other BTN3A-expressing lymphocytes such as αβ T or B cells. A first-in-human, phase 1/2a, open-label, clinical study of ICT01 was thus initiated in patients with advanced-stage solid tumors (EVICTION: NCT04243499; EudraCT: 2019-003847-31). Preliminary results show that ICT01 was well tolerated and pharmacodynamically active in the first patients. Digital pathology analysis of tumor biopsies of a patient with melanoma suggests that ICT01 may promote immune cell infiltration within the tumor microenvironment.