Chapters authored
Biobetters: IFN-α2b Variants with Reduced Immunogenicity for the Treatment of Human Viral Diseases
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.
Part of the book: Antiviral Strategies in the Treatment of Human and Animal Viral Infections
Immunogenicity Study of Biosimilar Candidates
Therapeutic proteins can induce undesirable immune reactions in the patient and constitute a major concern as they may compromise therapy safety and efficacy. During the comparability study between a biosimilar product and the innovator, several attributes are considered. Among them, the comparative immunogenicity analysis in preclinical and clinical stages has a major relevance. In this chapter, we will describe the most used experimental platforms for biotherapeutic immunogenicity characterization. Special emphasis will be placed on in vitro assays for the detection of contaminants that modulate innate immune responses, as well as tools for the identification of biologic-derived T-cell epitopes. Likewise, we will also review the current trials used for the detection of host cell proteins (HCPs) and their potential impact on protein immunogenicity. Finally, we will analyze the admissibility criteria established by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), when comparing the immunogenicity of reference products and biosimilar candidates.
Part of the book: Drug Development and Safety