Anti-Human TL1A Monoclonal Antibody (Afimkibart)

TL1A (also called TNFSF15, VEGI) is a 23-kDa type-II transmembrane cytokine of the TNF superfamily that forms homotrimers and is expressed by endothelial cells, monocytes, dendritic cells and fibroblasts; upon cleavage to soluble TL1A it binds chiefly to death receptor 3 (DR3/TNFRSF25) and, to a lesser extent, decoy receptor 3 (DcR3/TNFRSF6B), triggering TRADD/RIPK1/TRAF2-mediated activation of NF-κB and MAPK cascades that drive production of IFN-γ, TNF-α, IL-2, IL-5, IL-13 and IL-9, thereby amplifying Th1, Th2, Th9 and Th17 responses, enhancing NK-cell cytotoxicity, promoting dendritic-cell maturation and leukocyte chemotaxis, and, depending on context, inducing caspase-8/3-dependent apoptosis or necroptosis, while also inhibiting endothelial proliferation and angiogenesis; dysregulated TL1A is implicated in Crohn’s disease, ulcerative colitis, rheumatoid arthritis, psoriasis, asthma and cancer, making it an attractive therapeutic target.