Overcoming immunogenicity associated with the use of biopharmaceuticals

Abstract

The safety and efficacy of biopharmaceuticals can be severely impaired by their immunogenicity. A risk-based strategy should be used to assess immunogenicity on a case-by-case basis using standardized methods to correlate anti-drug antibody levels with clinical outcome. In silico and in vitro techniques allow putative T-cell epitopes to be identified and eliminated in candidate molecules while maintaining structure and function. Putative T-cell epitopes can be studied in the context of the HLA allotypes representative of the target population in vitro and in transgenic mice that express human HLA genes. Mice immune tolerant to human proteins allow the study of the effect of factors such as aggregation on the loss of immune tolerance. However, significant challenges remain in order to be able predict the immunogenicity of a therapeutic protein in a particular individual.

Keywords::

• biopharmaceutical
• cytokine
• growth factors
• immunogenicity
• monoclonal antibody

Financial & competing interests disclosure

The work by Christophe Lallemand, Julie Legrand and Michael Tovey discussed in this article was funded in part by the Centre National de la Recherche Scientifique and Biomonitor Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.