earticle

영어

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) have been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. Models of murine tumor angiogenesis and receptor-specific antibodies are required to
evaluate roles of VEGF receptors in mouse xenograft models of human cancer. Human VEGFR-2 (also known as kinase insert domaincontaining receptor, KDR) and murine VEGFR-2 (or Fetal liver kinase-1, Flk-1) share 85% amino acid sequence identity in their extracellular domain. However, sequence homology of VEGF binding domain of KDR and Flk1 is less than 75%. Until now, none of available KDR neutralizing antibodies has species crossreactivity. We first describe here the development of fully human antibodies that cross-react with mouse, rat and human VEGFR-2. High-affinity, species cross-reactive, ScFv antibodies specific for KDR/Flk-1 were
selected from fully human naïve antibody phage display library we constructed. The selected and converted fully human IgG antibodies were found to bind to purified KDR with sub-nanomolar affinity. Their binding epitope locate in the IgG like domain 3 of extracellular domain of VEGFR-2, which is responsible for neutralizing effect of KDR function. I will discuss about recent in vivo data and part of preclinical data of anti-KDR antibody.