title: Human/mouse cross-reactive anti-VEGF receptor 2 recombinant antibodies selected from an immune b9 allotype rabbit antibody library.
abstract: Vascular endothelial growth factor (VEGF) and its receptors 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 models of human cancer. Human VEGFR2 (also known as KDR) and murine VEGFR2 (or Flk-1) share 85% amino acid sequence identity in their extracellular domain. We describe here the development of antibodies that cross-react with mouse and human VEGFR2. High-affinity, species cross-reactive, Fabs specific for KDR/Flk-1 were selected from an antibody phage display library generated from an immunized rabbit of b9 allotype. The selected chimeric rabbit/human Fabs were found to bind to purified KDR and Flk-1 with nanomolar affinity. Three of the selected Fabs detected KDR expression on human endothelial cells as well as Flk-1 on murine endothelial cells. The availability of anti-VEGFR2 Fab with species cross-reactivity will help to decipher the functional role of KDR/Flk-1 in tumor biology as well as facilitate the preclinical evaluation of the suitability of KDR/Flk-1 for drug targeting. This report underscores our earlier finding that b9 rabbits are excellent sources for high-affinity cross-reactive antibodies with therapeutic potential.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Popkov
authors.forename: Nina
authors.initials: N
authors.lastname: Jendreyko
authors.forename: Gualberto
authors.initials: G
authors.lastname: Gonzalez-Sapienza
authors.forename: Rose G
authors.initials: RG
authors.lastname: Mage
authors.forename: Christoph
authors.initials: C
authors.lastname: Rader
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Barbas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D011485:Protein Binding; D011817:Rabbits; D016415:Sequence Alignment; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; D007126:Immunoglobulin Allotypes; D019151:Peptide Library; D040301:Vascular Endothelial Growth Factor Receptor-2