Species cross-reactivity of antibodies used to treat ophthalmic conditions
Files
(Published version)
Date
2016
Authors
Irani, Y.
Scotney, P.
Nash, A.
Williams, K.A.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Investigative Ophthalmology and Visual Science, 2016; 57(2):586-591
Statement of Responsibility
Yazad Irani, Pierre Scotney, Andrew Nash, and Keryn A. Williams
Conference Name
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.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.