Inhibition of vascular endothelial growth factor induced mitogenesis of human endothelial cells by a chimeric anti-kinase insert domain-containing receptor antibody

The kinase insert domain-containing receptor (KDR) is the human vascular en dothelial growth factor (VEGF) receptor responsible for the mitogenic and a ngiogenic effects of VEGF. There is much experimental evidence to suggest t hat the VEGF/ KDR pathway plays an important role in tumor angiogenesis, a process essential for tumor growth and metastasis. Here we produced a chime ric anti-KDR antibody (IgG(1)), c-p1C11, from a single chain (scFv) antibod y isolated from a phage display library. C-p1C11 binds specifically to the extracellular domain of soluble as well as cell-surface expressed KDR. It e ffectively blocks VEGF-KDR interaction and inhibits VEGF-stimulated activat ion of KDR and MAP kinases p44/p42 of human endothelial cells. Furthermore, c-p1C11 efficiently neutralizes VEGF-induced mitogenesis of human endothel ial cells. Our results suggest that antibodies against KDR have potential c linical applications in the treatment of cancer and other diseases where pa thological angiogenesis is involved. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.