May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
RhuFab V2 Inhibits VEGF-Isoforms-Stimulated HUVEC Proliferation
Author Affiliations & Notes
  • J. Lowe
    BioAnalytical R&D, Genentech Inc, South San Francisco, CA, United States
  • J. Araujo
    BioAnalytical R&D, Genentech Inc, South San Francisco, CA, United States
  • M. Palma
    BioAnalytical R&D, Genentech Inc, South San Francisco, CA, United States
  • Y. Wang
    BioAnalytical R&D, Genentech Inc, South San Francisco, CA, United States
  • J. Gaudreault
    Clinical and Experimental Pharmacology, Genentech Inc, South San Francisco, CA, United States
  • J. Yang
    Clinical and Experimental Pharmacology, Genentech Inc, South San Francisco, CA, United States
  • N. Yu
    Clinical and Experimental Pharmacology, Genentech Inc, South San Francisco, CA, United States
  • D. Fei
    Clinical and Experimental Pharmacology, Genentech Inc, South San Francisco, CA, United States
  • Footnotes
    Commercial Relationships  J. Lowe, Genentech E; J. Araujo, Genentech E; M. Palma, Genentech E; Y. Wang, Genentech E; J. Gaudreault, Genentech E; J. Yang, Genentech E; N. Yu, Genentech E; D. Fei, Genentech E.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1828. doi:
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    • Get Citation

      J. Lowe, J. Araujo, M. Palma, Y. Wang, J. Gaudreault, J. Yang, N. Yu, D. Fei; RhuFab V2 Inhibits VEGF-Isoforms-Stimulated HUVEC Proliferation . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1828.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: rhuFab V2, developed by Genentech as an anti-angiogenic therapeutic agent, is the Fab moiety of a high affinity version of recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF). Currently, rhuFab V2 is in phase III clinical trials for treating patients with the wet form of age-related macular degeneration (AMD). In this study, we examined currently available isoforms of VEGF to evaluate rhuFab V2’s binding capabilities as well as its biological activity on VEGF165-, VEGF121-, and VEGF110-induced human umbilical vein endothelial cells (HUVEC) proliferation. Methods: The binding of rhuFab V2 to VEGF isoforms was determined by Western Blot analysis and the BIAcore analysis. The biological activity of rhuFab V2 was demonstrated in a HUVEC proliferation assay using Alamar BlueTM fluorescence as an indicator. Results: Western Blot analysis demonstrated that rhuFab V2 is capable of binding all three VEGF isoforms. The binding of rhuFab V2 to VEGF165, VEGF121, and VEGF110 was also confirmed by the BIAcore analysis. The HUVEC proliferation assay showed all three VEGF isoforms were able to stimulate cell growth in a dose-dependent manner. VEGF165-, VEGF121-, and VEGF110-induced HUVEC proliferation was inhibited in a dose-dependent fashion by rhuFab V2 with an IC50 of 0.29 ± 0.07 nM (N=8), 0.48 ± 0.08 nM (N=8), and 0.27 ± 0.09 nM (N=8), respectively. Other recombinant humanized antibodies did not neutralize VEGF-isoforms-induced HUVEC proliferation demonstrating the binding specificity of rhuFab V2 to the three VEGF-isoforms. Conclusions: rhuFab V2 is capable of binding all three VEGF isoforms and thereby inhibits VEGF-isoforms-induced endothelial cell proliferation.

Keywords: age-related macular degeneration • growth factors/growth factor receptors • proliferation 
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