Abstract A50: Direct oncogene cancer killing and selective tumor Treg killing through the TNFR2 receptor via dominant antibody antagonists

Abstract

Abstract A major barrier to cancer immunotherapy is lack of selective inhibitors of the regulatory T cells (Tregs) of the cancer microenvironment and methods to directly kill tumors through novel surface oncogenes. Tumor necrosis factor receptor 2 (TNFR2) is a target protein with restricted expression on the most potent Tregs of the tumor infiltrate and on human tumors as a newly discovered human oncogene. We characterized the effect of TNFR2 antibody antagonists via TNFR2 in human samples from ovarian ascites compared to healthy controls. TNFR2 antagonists potently inhibited Treg proliferation with exponential potency and selectivity for the tumor microenvironment Tregs. Furthermore, common ovarian cancer cell lines such as OVCAR3 expressed the TNFR2 oncogene and were rapidly and completely killed by TNFR2 antagonistic antibodies. Dominant TNFR2 antagonists demonstrate tumor-specific Treg depletion. Blocking TNFR2 signaling with antagonist antibodies also creates a novel tool to possibly eliminate tumors expressing the TNFR2 oncogene and to more potently suppress Tregs of the tumor environment. Citation Format: Heather Torrey, John Butterworth, Toshi Mera, Yoshiaki Okubo, Limei Wang, Danielle Baum, Sarah Warden, Sara Plager, Daniel Huang, Eva Vanamee, Rosemary Foster, Denise Faustman. Direct oncogene cancer killing and selective tumor Treg killing through the TNFR2 receptor via dominant antibody antagonists. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A50.