Tumor necrosis factor receptor superfamily member 9 (4-1BB) (mouse) (4-1BB)

Tumor necrosis factor receptor superfamily member 9 (4-1BB), also known as CD137, is a potent costimulatory receptor primarily expressed on activated T cells, natural killer (NK) cells, and other immune populations in mice [1, 3, 17]. As a member of the TNFR superfamily, it provides critical survival and proliferation signals to CD8+ T cells upon binding its ligand, 4-1BBL, or through agonistic antibody stimulation [1, 11, 19]. In preclinical oncology research, 4-1BB agonists like the 3H3 and 1D8 clones have demonstrated significant anti-tumor efficacy by enhancing cytotoxic T-cell activity and establishing durable immune memory [18, 19, 22]. However, systemic activation of the 4-1BB pathway in mice is frequently associated with dose-limiting hepatotoxicity, characterized by liver inflammation and elevated transaminases [4, 6, 11]. This challenge has driven the development of next-generation therapeutic formats, such as bispecific or tumor-targeted antibodies, aimed at localizing immune activation to the tumor microenvironment [2, 10, 21]. Beyond cancer, 4-1BB plays a role in modulating autoimmune responses and enhancing immunity against viral infections [4, 14].

Other names

CD137ILA (Induced by lymphocyte activation)Ly63TNFRSF9T-cell antigen 4-1BB4-1BB ligand receptor

Agonism of the 4-1BB receptor to provide costimulatory signals to T cells and NK cells, enhancing their survival, proliferation, and effector functions.