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Yazad Irani, Pierre Scotney, Andrew Nash, Keryn A. Williams; Species Cross-Reactivity of Antibodies Used to Treat Ophthalmic Conditions. Invest. Ophthalmol. Vis. Sci. 2016;57(2):586-591. doi: 10.1167/iovs.15-18239.
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The species cross-reactivity of the monoclonal antibodies infliximab, bevacizumab, and an anti–VEGF-B antibody, 2H10, in humans and rodents was determined.
The binding of infliximab to human, mouse, and rat TNF-α, of bevacizumab to human, mouse, and rat VEGF-A, and of the 2H10 antibody to human, mouse, and rat VEGF-B was evaluated by ELISA. The sequence of human, mouse, and rat TNF-α and VEGF-A at the binding sites for infliximab and bevacizumab were compared.
Infliximab bound to human TNF-α, but no binding to mouse or rat TNF-α was detected between 10 pg/mL and 10 μg/ml. Sequence comparison of the binding site revealed four changes in mouse and five in rat TNF-α compared with human. Bevacizumab bound strongly to human VEGF-A, but showed 5-log weaker binding to both mouse and rat VEGF-A. There was a single amino acid substitution in mouse and rat VEGF-A at the bevacizumab binding site. The 2H10 antibody displayed a similar binding profile to human, mouse, and rat VEGF-B.
The species cross-reactivity of monoclonal antibodies should be determined prior to their use in preclinical animal models. The 2H10 antibody binds to human, mouse, and rat VEGF-B making it suitable for testing in rodent models of human disease.
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