Species cross-reactivity of antibodies used to treat ophthalmic conditions

Yazad Irani, Pierre Scotney, Andrew Nash, Keryn A. Williams

Research output: Contribution to journalArticlepeer-review

18 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 or Issued - 1 Feb 2016
Externally publishedYes

Keywords

  • Biologic
  • Human
  • Monoclonal antibody
  • Mouse
  • Rat
  • Species cross-reactivity
  • TNF-α
  • VEGF-A
  • VEGF-B

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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