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Type: Journal article
Title: Species cross-reactivity of antibodies used to treat ophthalmic conditions
Author: Irani, Y.
Scotney, P.
Nash, A.
Williams, K.
Citation: Investigative Ophthalmology and Visual Science, 2016; 57(2):586-591
Publisher: Association for Research in Vision and Ophthalmology
Issue Date: 2016
ISSN: 0146-0404
Statement of
Yazad Irani, Pierre Scotney, Andrew Nash, and Keryn A. Williams
Abstract: 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-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. Results: 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. 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.
Keywords: Biologic; species cross-reactivity; monoclonal antibody; TNF-α; VEGF-A; VEGF-B; human; mouse; rat
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DOI: 10.1167/iovs.15-18239
Appears in Collections:Aurora harvest 8
Opthalmology & Visual Sciences publications

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