Predictive power of preclinical studies in animals for the immunogenicity of recombinant therapeutic proteins in humans
Bugelski, P.J.; Treacy, G.
Current Opinion in Molecular Therapeutics 6(1): 10-16
2004
ISSN/ISBN: 1464-8431 PMID: 15011776 Document Number: 580313
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.
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