Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti-angiogenic therapeutic strategy

Cancer Metastasis Rev. 1998 Jun;17(2):155-61. doi: 10.1023/a:1006094117427.


Biological evidence suggests that interference with the function of the angiogenic growth factor receptor VEGFR2 (flk1/KDR) is a particularly promising strategy to inhibit tumor-induced angiogenesis. Proof of concept was established by developing a monoclonal rat anti-mouse VEGFR2 antibody (DC101) and showing that it potently blocked the binding of VEGF to its receptor, inhibited VEGF-induced signaling, and strongly blocked tumor growth in mice through an anti-angiogenic mechanism. Since DC101 does not cross-react with the human VEGFR2 KDR, anti-KDR monoclonal antibodies were generated by standard hybridoma technology and by using phage display library. High affinity antibodies (Kd = 4.9 x 10(-10)-1.1 x 10(-9) M) were found with both approaches. The anti-KDR antibodies compete on an equimolar basis with VEGF for binding to KDR and inhibit with similar potency the VEGF-induced signaling and mitogenesis in human endothelial cells. Although these antibodies cannot be tested for in vivo efficacy in standard murine tumor models because of lack of species cross-reactivity, the similarity of their in vitro properties with those of DC101 suggests that they may be effective in blocking KDR function in vivo.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use*
  • Humans
  • Mice
  • Neoplasms / blood supply*
  • Neoplasms / drug therapy*
  • Neoplasms, Experimental / blood supply
  • Neoplasms, Experimental / drug therapy
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / prevention & control*
  • Rats
  • Receptor Protein-Tyrosine Kinases / immunology*
  • Receptors, Growth Factor / immunology*
  • Receptors, Mitogen / immunology
  • Receptors, Vascular Endothelial Growth Factor
  • Signal Transduction / drug effects


  • Antibodies, Monoclonal
  • Receptors, Growth Factor
  • Receptors, Mitogen
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor