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(Investigative Ophthalmology and Visual Science. 2008;49:522-527.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.07-1175
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Interaction between Bevacizumab and Murine VEGF-A: A Reassessment

Lanlan Yu, Xiumin Wu, Zhiyong Cheng, Chingwei V. Lee, Jennifer LeCouter, Claudio Campa, Germaine Fuh, Henry Lowman, and Napoleone Ferrara

From Genentech, Inc., South San Francisco, California.

PURPOSE. Bevacizumab is a humanized anti-human VEGF-A monoclonal antibody (mAb) approved by the United States Food and Drug Administration for cancer therapy and used off label to treat neovascular age-related macular degeneration. Earlier studies characterized bevacizumab as species specific and lacking the ability to neutralize murine (m) VEGF-A. However, a recent study reported that bevacizumab is a potent inhibitor of hemangiogenesis and lymphangiogenesis in murine models. The authors sought to reassess the interaction between bevacizumab and mVEGF-A.

METHODS. The authors performed Western blot analysis, plasmon resonance by BIAcore, and endothelial cell proliferation assays to characterize the interaction between bevacizumab and mVEGF-A. They also tested whether bevacizumab had any effects in two in vivo murine models, laser-induced choroidal neovascularization (CNV) and melanoma growth.

RESULTS. Western blot detected a very weak interaction, but BIAcore detected no measurable interaction between mVEGF and bevacizumab. Bevacizumab failed to inhibit mVEGF-stimulated endothelial cell proliferation. In addition, bevacizumab was indistinguishable from the control antibody in the CNV and tumor models, whereas a cross-reactive anti–VEGF-A mAb had dramatic inhibitory effects.

CONCLUSIONS. Bevacizumab has an extremely weak interaction with mVEGF-A, which fails to result in immunoneutralization as assessed by several bioassays.




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eLetters:

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Bevacizumab and Murine VEGF-A
Claus Cursiefen
IOVS Online, 23 May 2008 [Full text]
Author Response: Bevacizumab and Murine VEGF-A
Napoleone Ferrara
IOVS Online, 23 May 2008 [Full text]

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