Human TL1A (TNFSF15) Antibody - Tulisokibart Biosimilar

TL1A background

Tumor necrosis factor (TNF)-like 1A (TL1A), also called TNFSF15, is a cytokine that belongs to the TNF superfamily. TL1A is produced by endothelial cells, activated dendritic cells, and macrophages. It is synthesized as a membrane-bound trimeric molecule. Alternative splicing or cleavage by the tumor necrosis factor-alpha converting enzyme results in soluble TL1A [1]. Both forms bind the homotrimeric transmembrane death receptor 3 (DR3), triggering TRADD/TRAF2/RIP signaling, and ultimately leading to NF-κB and MAPKs activation. Subsequent gene expression in target cells drives the production of pro-inflammatory cytokines and differentiation of T helper subsets [1].

Relevance for therapeutics development

TL1A is normally responsible for mediating protective immune responses. However, it can also play a role in chronic inflammatory disorders and have harmful impacts. Abnormal TL1A expression or TL1A overactivity promotes excessive inflammation and immune cell infiltration, contributing to tissue damage and further inflammation amplification [1]. Pharmaceutical companies have developed potent monoclonal antibodies to block TL1A signaling and stop the downstream inflammatory cascade and tissue damage.

Tulisokibart background

Tulisokibart (MK-7240 or PRA023 from Merck) is a fully human anti-hTL1A-hIgG1 mAb designed to target the human tumor necrosis factor-like cytokine 1A (TL1A). This antibody specifically interacts with TL1A, thus preventing its binding to the TL1A receptor [1]. This monoclonal antibody (mAb) is being investigated for the treatment of IBD (Crohn’s disease and ulcerative colitis) [2].

References:

1. Xu, W.-D., R. Li, and A.-F. Huang, 2022. Role of TL1A in Inflammatory Autoimmune Diseases: A Comprehensive Review. Frontiers in Immunology, 13(891328).
2. Sands, B.E., et al., 2024. Phase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis. N Engl J Med, 391(12): p. 1119-1129.