Author/Authors :
Tvorogov، نويسنده , , Denis and Anisimov، نويسنده , , Andrey and Zheng، نويسنده , , Wei and Leppنnen، نويسنده , , Veli-Matti and Tammela، نويسنده , , Tuomas and Laurinavicius، نويسنده , , Simonas and Holnthoner، نويسنده , , Wolfgang and Heloterن، نويسنده , , Hanna and Holopainen، نويسنده , , Tanja and Jeltsch، نويسنده , , Michael and Kalkkinen، نويسنده , , Nisse and Lankinen، نويسنده , , Hilkka and Ojala، نويسنده , , Pنivi M. and Alitalo، نويسنده , , Kari، نويسنده ,
Abstract :
Summary
dies 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.
