Tumor necrosis factor receptor superfamily member 9 (CD137) (CD137)

Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), commonly referred to as CD137 or 4-1BB, is a type I transmembrane protein that serves as a critical costimulatory receptor on activated T cells, natural killer (NK) cells, and other immune populations [3, 12, 16]. Upon activation by its ligand (4-1BBL) or agonistic antibodies, CD137 signaling promotes T-cell survival, proliferation, and enhanced cytotoxic activity, while also supporting the formation of long-lived memory T cells [15, 20, 22]. In oncology, CD137 is a high-priority target for immunotherapy, with several agonistic antibodies in clinical development aimed at boosting anti-tumor immune responses [3, 19]. However, the clinical progress of early agonists like urelumab was limited by significant dose-dependent hepatotoxicity, characterized by severe transaminitis [4, 5, 7]. To address these safety challenges, next-generation therapies such as bispecific antibodies and Fc-engineered agonists are being developed to provide more localized and controlled immune activation within the tumor microenvironment [15, 21]. Beyond its role in cancer, CD137 is also involved in the pathogenesis of autoimmune disorders and the immune response to various infectious agents [21, 23].

Other names

4-1BBTNFRSF9ILACDw137T-cell antigen ILA4-1BB ligand receptor

Agonism of the CD137 receptor to provide costimulatory signals to T cells and NK cells, enhancing anti-tumor immunity.