Tumor necrosis factor receptor superfamily member 9 (4-1BB) (TNFRSF9)

Tumor necrosis factor receptor superfamily member 9 (4-1BB), also known as CD137, is a potent costimulatory receptor expressed on activated T cells, natural killer (NK) cells, and other immune cells (UniProt Q07011). It plays a critical role in the regulation of the immune response by promoting the survival, expansion, and effector function of CD8+ T cells through the activation of NF-kappaB and MAPK signaling pathways (PMID: 29343438). In oncology, 4-1BB is a high-priority target for immunotherapy because its activation can enhance the anti-tumor activity of exhausted T cells within the tumor microenvironment (PMID: 30610175). While early systemic agonists like urelumab showed efficacy, they were limited by severe hepatotoxicity (PMID: 29343438). Newer approaches, such as the bispecific antibody givastomig (ABL111), utilize a dual-targeting strategy to activate 4-1BB only in the presence of tumor-associated antigens like Claudin 18.2, aiming to improve the therapeutic index by localizing immune activation to the tumor site (NCT04900363; ABL Bio).

Other names

CD1374-1BBInduced by lymphocyte activationILAT-cell antigen 4-1BB homologCDw137

Agonism of the 4-1BB receptor to provide costimulatory signals that enhance T-cell and NK-cell mediated anti-tumor activity.