Biobetters: IFN-α2b Variants with Reduced Immunogenicity for the Treatment of Human Viral Diseases

Abstract

For more than three decades, IFN-α2b has been widely used for the treatment of multiple human viral infections such as chronic hepatitis B and C, and certain types of cancers. However, IFN-α2b can be immunogenic, and these undesired immune responses can lead to a decrease in therapeutic efficacy. In addition, IFN-α therapy has also been associated with the progression of certain autoimmune diseases. For these reasons, the development of new IFN-α2b versions with reduced (or even null) immunogenicity has become the focus of several investigations. The “de-immunization” strategies usually involve several steps starting with T cell epitope identification and mutation of those immunogenic residues using immuno-informatics tools. Then, further experimental validation through in vitro and in vivo experimental platforms is needed to confirm in silico predictions. In this chapter, we will review the main strategies addressed so far to develop more effective and safer IFN-based therapies.