Researchers Find an Effective Way to Block Vascular Network Formation

A recent paper, published in Elsevier's Cancer Cell, details how researchers from Finland and Austria have been able to develop a monoclonal antibody that blocks VEGFR-3 homodimer and VEGFR-3/VEGFR-2 heterodimer formation, signal transduction. It is also able to stop ligand-induced migration and sprouting of microvascular endothelial cells.

This is vitally important for the prevention of angiogenesis of tumor cells as vascular endothelial growth factors (VEGF) stimulate endothelial sprouting and vascular network formation.

The full article, entitled 'Effective Suppression of Vascular Network Formation by Combination of Antibodies Blocking VEGFR Ligand Binding and Receptor Dimerization', is available through Elsevier: www.cell.com/cancer-cell/

Abstract

Antibodies that block vascular endothelial growth factor (VEGF) have become an integral part of antiangiogenic tumor therapy, and antibodies targeting other VEGFs and receptors (VEGFRs) are in clinical trials. Typically receptor-blocking antibodies are targeted to the VEGFR ligand-binding site. Here we describe a monoclonal antibody that inhibits VEGFR-3 homodimer and VEGFR-3/VEGFR-2 heterodimer formation, signal transduction, as well as ligand-induced migration and sprouting of microvascular endothelial cells. Importantly, we show that combined use of antibodies blocking ligand binding and receptor dimerization improves VEGFR inhibition and results in stronger inhibition of endothelial sprouting and vascular network formation in vivo. These results suggest that receptor dimerization inhibitors could be used to enhance antiangiogenic activity of antibodies blocking ligand binding in tumor therapy.