Medi9447: Enhancing Anti-Tumor Immunity By Targeting Cd73 In The Tumor Microenvironment

MEDI9447 is a monoclonal antibody specific for the ectoenzyme, CD73. Data is presented in support of the hypothesis that targeting the extracellular production of adenosine by CD73 reduces the immunosuppressive effects of adenosine. We report a range of activities for this antibody, including inhibition of both recombinant and cellular CD73 ectonucleotidase activity, relief from AMP-mediated lymphocyte suppression in vitro, and inhibition of syngeneic tumor growth. In contrast with many other cancer immunotherapy agents such as checkpoint inhibitors or T cell agonists, MEDI9447 drives changes in both myeloid and lymphoid infiltrating leukocyte populations within the tumor microenvironment. Changes include significant increases in CD8 effector cells and activated macrophages, as well as a reduction in the proportions of myeloid-derived suppressor cells (MDSC) and regulatory T lymphocytes. Furthermore, these changes correlate directly with responder and non-responder subpopulations within the arms of animal studies using syngeneic tumors. Data showing additive activity between MEDI9447 and other immune-mediated therapy antibodies demonstrates the importance of relieving adenosine-mediated immunosuppression within tumors. Citation Format: Carl Hay, Erin Sult, Qihui Huang, Scott Hammond, Kathy Mulgrew, Kelly McGlinchey, Stacy Fuhrmann, Raymond Rothstein, Edmund Poon, Ross Stewart, Robert Hollingsworth, Kris Sachsenmeier. MEDI9447: enhancing anti-tumor immunity by targeting CD73 In the tumor microenvironment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 285. doi:10.1158/1538-7445.AM2015-285