Antibody-Dependent Cellular Phagocytosis by Macrophages is a Novel Mechanism of Action of Elotuzumab.
Fiche publication
Date publication
juillet 2018
Journal
Molecular cancer therapeutics
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DETAPPE Alexandre
Tous les auteurs :
Kurdi AT, Glavey SV, Bezman NA, Jhatakia A, Guerriero JL, Manier S, Moschetta M, Mishima Y, Roccaro A, Detappe A, Liu CJ, Sacco A, Huynh D, Tai YT, Robbins MD, Azzi J, Ghobrial IM
Lien Pubmed
Résumé
Elotuzumab, a recently approved antibody for the treatment of multiple myeloma, has been shown to stimulate Fcγ receptor (FcγR)-mediated antibody-dependent cellular cytotoxicity by natural killer (NK) cells toward myeloma cells. The modulatory effects of elotuzumab on other effector cells in the tumor microenvironment, however, has not been fully explored. Antibody-dependent cellular phagocytosis (ADCP) is a mechanism by which macrophages contribute to antitumor potency of monoclonal antibodies. Herein, we studied the NK cell independent effect of elotuzumab on tumor-associated macrophages using a xenograft tumor model deficient in NK and adaptive immune cells. We demonstrate significant antitumor efficacy of single-agent elotuzumab in immunocompromised xenograft models of multiple myeloma, which is in part mediated by Fc-FcγR interaction of elotuzumab with macrophages. Elotuzumab is shown in this study to induce phenotypic activation of macrophages and mediates ADCP of myeloma cells though a FcγR-dependent manner Together, these findings propose a novel immune-mediated mechanism by which elotuzumab exerts anti-myeloma activity and helps to provide rationale for combination therapies that can enhance macrophage activity. .
Mots clés
Animals, Antibodies, Monoclonal, administration & dosage, Antibodies, Monoclonal, Humanized, administration & dosage, Antibody-Dependent Cell Cytotoxicity, drug effects, Cell Line, Tumor, Cell Proliferation, drug effects, Humans, Killer Cells, Natural, drug effects, Macrophages, drug effects, Mice, Multiple Myeloma, drug therapy, Phagocytosis, drug effects, Tumor Microenvironment, drug effects, Xenograft Model Antitumor Assays
Référence
Mol. Cancer Ther.. 2018 07;17(7):1454-1463