Cancer and Metastasis Reviews

, Volume 17, Issue 2, pp 155–161

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

  • Larry Witte
  • Daniel J. Hicklin
  • Zhenping Zhu
  • Bronislaw Pytowski
  • Helen Kotanides
  • Patricia Rockwell
  • Peter Böhlen
Article

DOI: 10.1023/A:1006094117427

Cite this article as:
Witte, L., Hicklin, D.J., Zhu, Z. et al. Cancer Metastasis Rev (1998) 17: 155. doi:10.1023/A:1006094117427

Abstract

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 × 101010 − 1.1 × 10109 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.

angiogenesis VEGF KDR monoclonal antibody 

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Larry Witte
    • 1
  • Daniel J. Hicklin
    • 1
  • Zhenping Zhu
    • 1
  • Bronislaw Pytowski
    • 1
  • Helen Kotanides
    • 1
  • Patricia Rockwell
    • 2
  • Peter Böhlen
    • 1
  1. 1.Department of Molecular and Cell Biology and Department of ImmunologyImClone Systems IncorporatedNew YorkUSA
  2. 2.Department of Biological SciencesHunter College of CUNYNew YorkUSA

Personalised recommendations