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shengjian li, Nagaraj Kerur, Sasha Bogdanovich, Reo Yasuma, Younghee Kim, Takeshi Mizutani, Ana Bastos-Carvalho, Jayakrishna Ambati; The Fc fragments of Bevacizumab or IVIG suppress choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1191.
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Choroidal neovascularization (CNV) in humans is often treated with full-length bevacizuman or the Fab fragment ranibizumab. Although bevacizumab does not bind or block mouse VEGF it has been reported to suppress mouse CNV. We tested the hypothesis that this anti-angiogenic effect of bevacizumab in mice was due not to mouse VEGF targeting but due to a novel effect of its Fc fragment. We tested Fab and Fc fragments of bevacizumab as well as of those of “intravenous human immunoglobulin” (IVIG), a widely used clinical therapeutic in mouse CNV.
Commercially supplied bevacizumab or IVIG was digested with Papain, and the further purified Fab and Fc fragments were tested in the laser injury CNV model in WT and Fcgr1-deficient mice. CNV size was quantified by volumetric assessment.
Bevacizumab-Fc and IVIG-Fc suppressed CNV in WT mice, whereas bevacizumab-Fab and IVIG-Fab did not do so. Bevacizumab-Fc and IVIG-Fc did not suppress CNV in Fcgr1-deficient mice.
These data identify a novel anti-angiogenic function of the Fc fragment of human immunoglobulin-containing therapeutic preparations and clarify earlier puzzling data of the bioactivity of bevacizumab in mice.
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