FAP-4-1BBL

FAP-4-1BBL is a bispecific antibody that specifically delivers 4-1BB (CD137, TNFRSF9) agonist activity to the tumor microenvironment by targeting fibroblast activation protein (FAP), which is expressed on cancer-associated fibroblasts. This dual targeting achieves **tumor-localized T cell costimulation and activation** only when both FAP and 4-1BB are engaged, reducing the risk of systemic toxicity found with conventional 4-1BB agonists. Mechanistically, the drug enhances T cell proliferation, cytokine production (such as IFN-γ, TNF-α, IL-2, and de novo secretion of IL-13), and tumor cell killing, especially when combined with T cell receptor (TCR) stimulation (e.g., CD3 engagement or T cell bispecific antibodies like cibisatamab). This approach amplifies the cytotoxic function of tumor-infiltrating lymphocytes and induces tumor cell apoptosis via mechanisms partly dependent on IL-13 signaling and STAT6 phosphorylation. The molecule is under investigation in early-phase clinical trials for solid tumors, notably non-small cell lung cancer and ovarian cancer, and is considered a next-generation tumor-specific immunotherapy[1][2][3].

Other names

fibroblast activation protein-targeted-4-1BB ligand agonist