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Human/mouse cross-reactive anti-VEGF receptor 2 recombinant antibodies selected from an immune b9 allotype rabbit antibody library.
- Source :
-
Journal of immunological methods [J Immunol Methods] 2004 May; Vol. 288 (1-2), pp. 149-64. - Publication Year :
- 2004
-
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.<br /> (Copyright 2004 Elsevier B.V.)
- Subjects :
- Amino Acid Sequence
Animals
Antibodies metabolism
Humans
Kinetics
Mice
Molecular Sequence Data
Protein Binding
Rabbits
Sequence Alignment
Vascular Endothelial Growth Factor Receptor-2 metabolism
Antibodies immunology
Immunoglobulin Allotypes immunology
Peptide Library
Vascular Endothelial Growth Factor Receptor-2 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1759
- Volume :
- 288
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Journal of immunological methods
- Publication Type :
- Academic Journal
- Accession number :
- 15183093
- Full Text :
- https://doi.org/10.1016/j.jim.2004.03.005