Species Cross-Reactivity of Antibodies Used to Treat Ophthalmic Conditions
Species Cross-Reactivity of Antibodies Used to Treat Ophthalmic Conditions
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DOI：
10.1167/iovs.15-18239
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发表时间：
2016-02-01
影响因子：
4.4
通讯作者：
Williams, Keryn A.
中科院分区：
文献类型：
--
作者：
Irani, Yazad;Scotney, Pierre;Williams, Keryn A.
PURPOSE. The species cross-reactivity of the monoclonal antibodies infliximab, bevacizumab, and an anti-VEGF-B antibody, 2H10, in humans and rodents was determined.METHODS. The binding of infliximab to human, mouse, and rat TNF-alpha, 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-alpha and VEGF-A at the binding sites for infliximab and bevacizumab were compared.RESULTS. Infliximab bound to human TNF-alpha, but no binding to mouse or rat TNF-alpha was detected between 10 pg/mL and 10 lg/ml. Sequence comparison of the binding site revealed four changes in mouse and five in rat TNF-alpha 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.CONCLUSIONS. 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.
