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 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.
Sauerborn
Melody
M
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht, the Netherlands. M.S.Sauerborn@uu.nl
Brinks
Vera
V
Jiskoot
Wim
W
Schellekens
Huub
H
D000818:Animals; D000906:Antibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D004921:Erythropoietin / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000276:immunology; D008213:Lymphocyte Activation; D011994:Recombinant Proteins / Q000276:immunology* / Q000627:therapeutic use*; D013950:Thymus Gland / Q000502:physiology
D000906:Antibodies; D007328:Insulin; D011994:Recombinant Proteins; D004921:Erythropoietin