Definition

A conditionally-active, fully human immunoglobulin G1 (IgG1) agonistic 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 AGEN2373 targets and binds to a non-ligand blocking epitope on CD137, thereby activating CD137 expressed on a variety of leukocyte subsets including activated T lymphocytes and natural killer (NK) cells. 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. In addition, as AGEN2373 engages with CD137 only in the presence of CD137 ligand and/or Fc gamma receptor-expressing antigen-presenting cells (APCs), this agent may have a decreased toxicity profile and improved tolerability compared to other agents that activate CD137 signaling beyond the tumor site in humans.