Interaction between bevacizumab and murine VEGF-A: a reassessment.

Abstract

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.

• Authors: Lanlan Yu, Xiumin Wu, Zhiyong Cheng, Chingwei V Lee, Jennifer LeCouter, Claudio Campa, Germaine Fuh, Henry Lowman, Napoleone Ferrara
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 49 Issue 2 Pg. 522-7 (Feb 2008) ISSN: 0146-0404 [Print] United States
• PMID: 18234994 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Bevacizumab

Topics

• Angiogenesis Inhibitors (metabolism, pharmacology)
• Animals
• Antibodies, Monoclonal (metabolism, pharmacology)
• Antibodies, Monoclonal, Humanized
• Bevacizumab
• Blotting, Western
• Cattle
• Cell Proliferation (drug effects)
• Choroidal Neovascularization (pathology)
• Drug Interactions
• Electrophoresis, Polyacrylamide Gel
• Endothelium, Vascular (drug effects)
• Female
• Melanoma, Experimental (pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Nude
• Skin Neoplasms (pathology)
• Surface Plasmon Resonance
• Vascular Endothelial Growth Factor A (metabolism, pharmacology)