Denise L. Faustman
Massachusetts General Hospital/Harvard Medical School, USA
Posters & Accepted Abstracts: Oncol Cancer Case Rep
A major barrier to cancer immunotherapy is the lack of selective inhibitors of the regulatory T cells (Tregs) of the cancer microenvironment. New methods to directly kill tumors through novel surface oncogenes are also desirable in this setting. 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 and broadly expressed human oncogene. We characterized the expression and the functional effects of newly created TNFR2 antibody antagonists on the tumor infiltrating Tregs of ovarian ascites compared to Tregs of peripheral blood from both patients and healthy controls. We also investigated if well known ovarian tumor cells lines express the TNFR2 oncogene and the effects of the TNFR2 antagonistic antibody on direct cancer killing. We found that TNFR2 antagonists inhibited Treg proliferation with exponential potency and selectivity for 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, even at low concentrations. We conclude that dominant TNFR2 antagonists demonstrate tumor-specific Treg depletion with heightened specificity for the tumor microenvironment over the Tregs of peripheral blood. Blocking TNFR2 signaling with antagonist antibodies also creates a novel tool to directly eliminate ovarian tumors expressing the TNFR2 oncogene.