An in vitro Comparison of the Binding Kinetics of Bevacizumab and Ranibizumab to VEGF-165

Abstract

Purpose: : Previous publications have stated that Ranibizumab is 10 to 15 times more potent than Bevacizumab, based upon unpublished bioassays measuring VEGF-induced endothelial cell mitogenesis. To test this assertion, and to provide quantitative in vitro data that can complement current clinical trials comparing these two agents, we directly compared the in vitro kinetic constants of Bevacizumab and Ranibizumab.

Methods: : Surface plasmon resonance was utilized to measure association and disassociation constants of Bevacizumab and Ranibizumab binding to VEGF-165, as well as to perform a competitive binding assay of Bevacizumab and Ranibizumab.

Results: : Different concentrations of Bevacizumab and Ranibizumab were made to flow over a VEGF-coated surface. We find that the maximum response, the association constant (k_a[M^-1s^-1], ~10⁴) and the disassociation constant (k_a[M^-1s^-1], negligible over 24 hours) of Bevacizumab and Ranibizumab were similar, within the measurement errors of the experimental system. Our findings are consistent with other surface plasmon resonance measurements of VEGF-binding compounds.

Conclusions: : In vitro Bevacizumab and Ranibizumab have similar association kinetics. Quantitative measurements of the kinetics and binding of anti-VEGF therapeutics to VEGF-165 allow another, objective measure of the function of these therapeutic compounds.

Keywords: age-related macular degeneration • retinal neovascularization • choroid: neovascularization