Definition

A bispecific antibody targeting Delta-like ligand 4 (DLL4) and vascular endothelial growth factor A (VEGF-A), with potential anti-angiogenic and antineoplastic activities. Upon administration, anti-DLL4/anti-VEGF-A bispecific antibody CTX-009 simultaneously targets, binds to and blocks DLL4 and VEGF-A. This prevents the activation of DLL-4/Notch- and VEGF-A/VEGF receptor (VEGFR)-mediated signaling pathways, which play key roles in angiogenesis and tumor vascularization. This prevents angiogenesis and may halt tumor cell proliferation. Activation of Notch receptors by DLL4 stimulates proteolytic cleavage of the Notch intracellular domain (NICD); after cleavage, NICD is translocated to the nucleus and mediates the transcriptional regulation of a variety of genes involved in vascular development. The expression of DLL4 is highly restricted to the vascular endothelium; DLL4/Notch signaling is required for the development of functional tumor blood vessels. VEGF-A is upregulated in a variety of cancer cell types and plays a crucial role in angiogenesis.