NOVEL ANTIBODIES DIRECTED AGAINST THE EXTRACELLULAR DOMAIN OF THE HUMAN VEGF-RECEPTOR TYPE-II

Vascular endothelial cell growth factor (VEGF) plays a pivotal role in the regulation of angiogenesis by binding to its cognate receptor mol ecule type II (VEGFr-II, KDR). VEGFr-II is an endothelial cell-specifi c transmembrane tyrosine kinase important for vascular endothelial cel l development and differentiation during embryogenesis, angiogenic pro cesses under physiological conditions, and various diseases, An increa sing number of reports indicate that VEGF/VEGFr-II also play a fundame ntal role for tumor angiogenesis. We present the generation and in vit ro characterization of the monoclonal antibodies 2-7-9 and 2-10-1. Bot h antibodies are highly specific for VEGFr-II as demonstrated by Weste rn blotting and immunoprecipitation. MAbs 2-10-1 and 2-7-9 bind to a d isulphide bridge-stabilized epitope within domains 6 and 7 of the huma n VEGFr-II with an affinity of 8 and 80 nM, respectively. Furthermore, the antibodies are suitable for immunohistochemistry and ELISA techni ques, Because both antibodies recognize their epitope on living cells, they also have the potential for drug targeting and diagnostic purpos es.