Antibody-mediated targeting of TNFR2 activates CD8 + T cells in mice and promotes antitumor immunity.

Tumor necrosis factor receptor 2 (TNFR2) is the alternate receptor for TNF and can mediate both pro- and anti-inflammatory activities of T cells. Although TNFR2 has been linked to enhanced suppressive activity of regulatory T cells (T-regs) in autoimmune diseases, the viability of TNFR2 as a target for cancer immunotherapy has been under-appreciated. Here, we show that new murine monoclonal anti-TNFR2 antibodies yield robust antitumor activity and durable protective memory inmultiplemouse cancer cell linemodels. The antibodies mediate potent Fc-dependent T cell costimulation and do not result in significant depletion of T-regs. Corresponding human agonistic monoclonal anti-TNFR2 antibodies were identified and also had antitumor effects in humanized mousemodels. Anti-TNFR2 antibodies could be developed as a novel treatment option for patients with cancer.