4-1BB ligand

4-1BBL (4-1BB ligand), also known as TNFSF9 or CD137L, is a type II transmembrane protein and a member of the tumor necrosis factor (TNF) superfamily. It acts as the endogenous ligand for the 4-1BB (CD137) receptor, a potent co-stimulatory molecule expressed on activated T cells, natural killer (NK) cells, and dendritic cells. Binding of 4-1BBL to 4-1BB activates downstream NF-κB, c-Jun, and p38 MAPK signaling pathways, leading to enhanced T-cell proliferation, cytokine production (such as IFN-γ), and improved survival of effector and memory T cells. In oncology, 4-1BBL is being developed as a therapeutic agent in several formats to provide localized immune stimulation within the tumor microenvironment. These include recombinant fusion proteins (e.g., FAP-4-1BBL), gene-engineered oncolytic viruses (e.g., LOAd703), and cellular therapies (e.g., RTX-240) that express 4-1BBL to supercharge the immune response against solid tumors and hematological malignancies. By agonizing the 4-1BB receptor, these therapies aim to promote durable anti-tumor immunity while minimizing the systemic toxicities associated with agonistic 4-1BB antibodies.

Other names

4-1BBLCD137 ligandCD-137 ligandCD 137 ligandTumor necrosis factor ligand superfamily member 9