anti-DLL4 antibody

Anti-DLL4 antibodies are a class of therapeutic monoclonal antibodies designed to inhibit Delta-like ligand 4 (DLL4), a critical component of the Notch signaling pathway that is frequently overexpressed in the tumor vasculature and certain cancer cells. By binding to DLL4, these antibodies prevent its interaction with Notch receptors (primarily Notch1), leading to two primary anti-tumor effects: first, they induce "unproductive angiogenesis," characterized by an increase in non-functional, leaky vascular sprouting that reduces overall tumor perfusion; second, they directly inhibit the self-renewal and survival of cancer stem cells (CSCs) and reverse the epithelial-to-mesenchymal transition (EMT), which are key drivers of tumor recurrence and chemoresistance. Prominent examples in this class include OncoMed Pharmaceuticals' demcizumab (OMP-21M18), Regeneron's enoticumab (REGN421), and AstraZeneca's MEDI0639. While preclinical studies demonstrated significant efficacy in delaying tumor recurrence and overcoming drug resistance in models of pancreatic, breast, and lung cancer, clinical development has been hampered by safety concerns, including hypertension and congestive heart failure, as well as a lack of significant survival benefit in Phase 2 trials.

Other names

DLL4 inhibitorDLL-4 inhibitorDLL 4 inhibitorDelta-like 4 antibodyDelta-like4 antibodyDelta-like-4 antibodyanti-Delta-like 4 antibodyanti-Delta-like4 antibodyanti-Delta-like-4 antibodyDelta-like 4 antagonistDelta-like4 antagonistDelta-like-4 antagonist