Definition

A humanized agonistic immunoglobulin G4 (IgG4) monoclonal antibody targeting the costimulatory receptor CD137 (4-1BB; tumor necrosis factor receptor superfamily member 9; TNFRSF9), with potential immunostimulating and antineoplastic activities. Upon administration, anti-CD137 agonistic monoclonal antibody ATOR-1017 targets and binds to CD137 expressed on a variety of leukocyte subsets including activated T-lymphocytes and natural killer (NK) cells, and CD137 is activated upon crosslinking to Fc-gamma receptors (FcgRs) on macrophages. This enhances CD137-mediated signaling, induces cytotoxic T-lymphocyte (CTL) proliferation, cytokine production and promotes a CTL-mediated anti-tumor immune response as well as induces NK-mediated tumor cell killing and suppresses the immunosuppressive activity of T-regulatory cells (Tregs). CD137, a surface glycoprotein of the tumor necrosis factor receptor superfamily, is an inducible costimulatory receptor that plays a key role in T-cell proliferation, survival and cytolytic activity. 4-1BB and FcgRs are both highly expressed in the tumor environment (TME) while their co-expression in non-tumor tissues is low. This may prevent systemic adverse effects.