Interaction between bevacizumab and murine VEGF-A: a reassessment.
OBJECTIVE
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.
Yu
Lanlan
L
Genentech Inc, South San Francisco, CA 94080, USA.
Wu
Xiumin
X
Cheng
Zhiyong
Z
Lee
Chingwei V
CV
LeCouter
Jennifer
J
Campa
Claudio
C
Fuh
Germaine
G
Lowman
Henry
H
Ferrara
Napoleone
N
D020533:Angiogenesis Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015153:Blotting, Western; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000473:pathology; D004347:Drug Interactions; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012878:Skin Neoplasms / Q000473:pathology; D020349:Surface Plasmon Resonance; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000068258:Bevacizumab