Immunological mechanism underlying the immune response to recombinant human protein therapeutics

Recombinant human (rhu) protein therapeutics are powerful tools to treat several severe diseases such as multiple sclerosis and diabetes mellitus, among others. A major drawback of these proteins is the production of anti-drug antibodies (ADAs). In some cases, these ADAs have neutralizing capacity a...

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Bibliographic Details
Published in:Trends in pharmacological sciences (Regular ed.) 2010-02, Vol.31 (2), p.53-59
Main Authors: Sauerborn, Melody, Brinks, Vera, Jiskoot, Wim, Schellekens, Huub
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Antibodies - blood
B-Lymphocytes - immunology
Erythropoietin - immunology
Humans
Insulin - immunology
Lymphocyte Activation
Recombinant Proteins - immunology
Recombinant Proteins - therapeutic use
Thymus Gland - physiology
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Summary:Recombinant human (rhu) protein therapeutics are powerful tools to treat several severe diseases such as multiple sclerosis and diabetes mellitus, among others. A major drawback of these proteins is the production of anti-drug antibodies (ADAs). In some cases, these ADAs have neutralizing capacity and can interfere with the efficacy and safety of the drug. Little is known about the immunological mechanisms underlying the unwanted immune response against human homolog protein therapeutics. This article aims to provide current insights into recent immunological developments and to link this with regard to production of ADAs. A particular focus is given to aggregates being present in a rhu protein formulation and their impact on the immune system, subsequently leading to breakage of tolerance and formation of ADAs. Aggregation is one of the key factors in immunogenicity and by reducing aggregation one can reduce immunogenicity and make drugs safer and more efficient.
ISSN:0165-6147
1873-3735
DOI:10.1016/j.tips.2009.11.001