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Int Rev Cell Mol Biol. 2016;326:343-72. doi: 10.1016/bs.ircmb.2016.06.001. Epub 2016 Jul 20.

Interferon Beta: From Molecular Level to Therapeutic Effects.

Author information

1
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, Netherlands.
2
Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, CA, United States.
3
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, Netherlands. Electronic address: H.Schellekens@uu.nl.

Abstract

Interferon beta (IFNβ) is a cytokine that is naturally produced by the immune system in response to biological and chemical stimuli. It signals by binding to the heterodimeric type I IFN receptor composed of the IFNAR1 and IFNAR2 chains, and regulates the expression of a plethora of genes by means of the classical JAK/STAT and other pathways. IFNβ is pleiotropic in that it elicits antiviral, antiproliferative, and immunomodulatory activities on numerous cell types. The biological activities underpin the mechanisms by which the protein is used to treat various diseases such as hepatitis C infection and multiple sclerosis. Despite the success of IFNβ therapy, the drug may evoke the production of antidrug antibodies that may reduce treatment efficiency. Immunogenicity is related to many factors: among them, structural properties, particularly aggregation, and T-cell and B-cell epitopes in the structure of IFNβ, appear to be important. Knowledge of the structural properties of IFNβ and its relation to immunogenicity may help scientists to develop safer and more effective forms. Several methods have been used to predict and reduce the immunogenicity of certain IFNβ drug products. In this chapter, we review the current knowledge on IFNβ from its structure, dynamic conformation, signaling pathway, and mechanism of action to its therapeutic effects. Immunogenicity and its relation to structural properties of IFNβ are also discussed.

KEYWORDS:

antibodies; epitopes; immunogenicity; interferon beta; molecular aggregates; multiple sclerosis

PMID:
27572132
DOI:
10.1016/bs.ircmb.2016.06.001
[Indexed for MEDLINE]

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