Comparing protein VEGF inhibitors: In vitro biological studies

Biochem Biophys Res Commun. 2011 May 6;408(2):276-81. doi: 10.1016/j.bbrc.2011.04.014. Epub 2011 Apr 8.

Abstract

VEGF inhibitors are widely used as a therapy for tumors and intravascular neovascular disorders, but limited and conflicting data regarding their relative biological potencies are available. The purpose of the study is to compare different protein VEGF inhibitors for their ability to inhibit VEGF-stimulated activities. We tested ranibizumab, the full-length variant of ranibizumab (Mab Y0317), bevacizumab, the VEGF-TrapR1R2 and Flt(1-3)-IgG in bioassays measuring VEGF-stimulated proliferation of bovine retinal microvascular endothelial cells or chemotaxis of human umbilical vein endothelial cells (HUVEC). The inhibitors were also compared for their ability to inhibit MAP kinase activation in HUVECs following VEGF addition. Ranibizumab, VEGF-TrapR1R2 and Flt(1-3)-IgG had very similar potencies in the bioassays tested. Bevacizumab was over 10-fold less potent than these molecules. Mab Y0317 was over 30-fold more potent than bevacizumab. The findings reported in this manuscript describe important intrinsic characteristics of several VEGF inhibitors that may be useful to design and interpret preclinical or clinical studies.

Publication types

  • Comparative Study

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Biological Assay
  • Cattle
  • Cells, Cultured
  • Chemotaxis / drug effects
  • Endothelium, Vascular / drug effects*
  • Humans
  • Immunoglobulin G
  • Ranibizumab
  • Receptors, Growth Factor
  • Recombinant Fusion Proteins / pharmacology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-1

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Flt(1-3)-IgG
  • Immunoglobulin G
  • Receptors, Growth Factor
  • Recombinant Fusion Proteins
  • VEGF Trap R1R2 protein
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Vascular Endothelial Growth Factor Receptor-1
  • Ranibizumab