title: Species Cross-Reactivity of Antibodies Used to Treat Ophthalmic Conditions.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology Flinders University, Bedford Park, South Australia, Australia.
authors.forename: Yazad
authors.initials: Y
authors.lastname: Irani
authors.affiliation: CSL Limited, Parkville, Victoria, Australia.
authors.forename: Pierre
authors.initials: P
authors.lastname: Scotney
authors.affiliation: CSL Limited, Parkville, Victoria, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Nash
authors.affiliation: Department of Ophthalmology Flinders University, Bedford Park, South Australia, Australia.
authors.forename: Keryn A
authors.initials: KA
authors.lastname: Williams
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000068258:Bevacizumab / Q000276:immunology / Q000494:pharmacology*; D001666:Binding Sites, Antibody / Q000276:immunology*; D003429:Cross Reactions; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000069285:Infliximab / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D051381:Rats; D012164:Retinal Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014822:Vitreous Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069285:Infliximab