DLL4/VEGF Antibodies

Target Information

Delta-like ligand 4 (DLL4), also know as Delta-4, is a homologue of the Drosophila delta protein, and functions as a transmembrane bound ligand to the notch receptor Notch1. DLL4 is expressed in the vasculature and plays a critical role in vascular development. It is induced by vascular endothelial growth factor (VEGF), as a negative feedback regulator to regulate angiogenic sprouting and promote the formulation of a differentiated vascular network. DLL4 has been found to be strongly expressed in tumor vessels of clear-cell renal tumors and bladder cancer, and inhibition of DLL4 results in increased vascular proliferation but defective maturation. This in turn leads to a decrease in tumor growth, with no apparent toxicity.

VEGF (vascular endothelial growth factor) which is a 45 kDa homodimeric, disulfide-linked glycoprotein involved in angiogenesis which promotes tumor progression and metastasis. VEGF has a variety of effects on vascular endothelium, including the ability to promote endothelial cell viability, mitogenesis, chemotaxis, and vascular permeability. The VEGF family currently includes VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and PIGF. VEGF and its receptor system have been shown to be the fundamental regulators in the cell signaling of angiogenesis. Most tumors have the absolute requirement of angiogenesis, and VEGF has been described as the most potent angiogenic cytokine linked to this process. To date 5 different isoforms of VEGF have been described. These isoforms are generated as the result of alternative splicing from a single VEGF gene. These various isoforms have been shown to bind to two tyrosine-kinase receptors flt-1 (VEGFR-1) and flk-1/KDR (VEGFR-2), which have been found to be expressed almost exclusively on endothelial cells. VEGF and its high-affinity binding receptors, the tyrosine kinases FLK1 and FLT1, are thought to be important for the development of embryonic vasculature. Studies have shown that an alternately spliced form of FLT1 produces a soluble protein, termed sFLT1, which binds vascular endothelial growth factor with high affinity, playing an inhibitory role in angiogenesis. Elevated levels of VEGF is linked to POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) also known as Crow-Fukase syndrome which affects multiple organs in the body.