Can we prevent immunogenicity of human protein drugs?
Monoclonal antibodies have proved to be extremely valuable additions to conventional treatment for rheumatic diseases. However, despite the general trend towards "humanisation", these drugs remain immunogenic in clinical settings, baffling drug developers. In principle, humanised and fully human monoclonal antibodies are "self" immunoglobulins and should be tolerated. In this overview, the factors that may influence this process, the nature of immunogenicity and methods to analyse and modify potential immunogenicity are discussed. Finally, novel approaches to "re-induce" immunological tolerance to these proteins, including gene therapy and the recognition of unique regulatory epitopes, are outlined.
Scott
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Department of Surgery, Microbiology, University of Maryland School of Medicine, Center for Vascular and Inflammatory Diseases, 800 West Baltimore St, Baltimore, MD 21201, USA. davscott@som.umaryland.edu
De Groot
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D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D015195:Drug Design; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007108:Immune Tolerance
D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte