Blocking Antibodies Targeting the CD39/CD73 Immunosuppressive Pathway Unleash Immune Responses in Combination Cancer Therapies

• DOI: 10.1016/j.celrep.2019.04.091
• Publication Date: 2019-05-21T15:15:33Z
• Authors: Ivan Perrot; Henri-Alexandre M...; Marc Giraudon-Paoli; Séverine Augier; Aurélie Docquier; Laurent Gros; Rachel Courtois; Cécile Déjou; Diana Jecko; Ondine Becquart; Hélène Rispaud-Blanc; Laurent Gauthier; Benjamin Rossi; Stéphanie Chanteux; Nicolas Gourdin; Beatrice Amigues; Alain Roussel; Armand Bensussan; Jean-François Eliaou; Jérémy Bastid; François Romagné; Yannis Morel; Emilie Narni-Manc...; Eric Vivier; Carine Paturel; Nathalie Bonnefoy
• Keywords: Immune checkpoint; Blocking antibody; Cancer Immunotherapy

Immune checkpoint inhibitors have revolutionized cancer treatment. However, many cancers are resistant to ICIs, and the targeting of additional inhibitory signals is crucial for limiting tumor evasion. The production adenosine via sequential activity CD39 CD73 ectoenzymes participates generation an immunosuppressive microenvironment. In order disrupt pathway, we generated two antibodies, IPH5201 IPH5301, human membrane-associated soluble forms CD73, respectively, efficiently blocking hydrolysis immunogenic ATP into adenosine. These antibodies promoted antitumor immunity by stimulating dendritic cells macrophages restoring activation T isolated from patients. a knockin mouse preclinical model, increased anti-tumor ATP-inducing chemotherapeutic drug oxaliplatin. results support use anti-CD39 anti-CD73 monoclonal their combination with immune chemotherapies in cancer.