Species Cross-Reactivity of Antibodies Used to Treat Ophthalmic Conditions

Yazad Irani, Pierre Scotney, Andrew Nash, Keryn Williams

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    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-a, but no binding to mouse or rat TNF-α was detected between 10 pg/mL and 10 mg/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.

    Original languageEnglish
    Pages (from-to)586-591
    Number of pages6
    JournalInvestigative Ophthalmology and Visual Science
    Volume57
    Issue number2
    DOIs
    Publication statusPublished - 2016

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