title: Predictive power of preclinical studies in animals for the immunogenicity of recombinant therapeutic proteins in humans.
abstract: Despite advances at the level of gene sequence (eg, humanized versus murine antibodies), expression systems (eg, mammalian versus prokaryotic) and post-expression modification (eg, 'PEGylation'), clinical immunogenicity of therapeutic proteins remains a concern. Although animals are routinely and effectively used to evaluate pharmacological activity and to support a claim of safety for recombinant proteins, their usefulness for predicting clinical immunogenicity is more questionable. This review argues that recombinant proteins can be grouped into immunogenic classes; for some of these classes, for example, bacterial proteins, immunogenicity in animals is often predictive for humans, but for others, for example, fully human proteins, even data from non-human primates can have little predictive value. We will attempt to make the case that for a variety of immunological and practical constraints, animal studies, even those conducted in non-human primates, have limited predictive power for immunogenicity in humans, and tend to over-predict clinical immunogenicity.
authors.affiliation: Centocor Inc, Toxicology and Investigational Pharmacology, 200 Great Valley Parkway, Malvern, PA 19355, USA. pbugelsk@cntus.jnj.com
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bugelski
authors.forename: George
authors.initials: G
authors.lastname: Treacy
mesh_terms: D000818:Animals; D000830:Animals, Laboratory; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000941:Antigens; D011994:Recombinant Proteins