Biobetters: IFN-alpha 2b variants with reduced immunogenicity for the treatment of human viral diseases

EDUARDO MUFARREGE; LUCÍA PEÑA; MARINA ECHEVERRIGARAY

Antiviral Strategies in the Treatment of Human and Animal Viral Infections

IntechOpen

Lugar: Londres; Año: 2023;

For more than three decades, IFN-alpha2b 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-alpha2b can be immunogenic, and these undesired immune responses can lead to a decrease in therapeutic efficacy. In addition, IFN-alpha therapy has also been associated with the progression of certain autoimmune diseases.For these reasons, the development of new IFN-alpha2b 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.