Eukaryotic Expression Systems for Upstream Processing of Monoclonal Antibodies

What You Will Learn in This ChapterMonoclonal antibodies (mAbs) represent the largest group of biopharmaceuticals used for human therapy, diagnostics, and imaging. Full-length mAbs with human-like posttranslational modifications are almost exclusively expressed in mammalian cell cultures. Progress in genetic engineering techniques and process development enables the development of optimized cell lines and manufacturing processes. The main factors that influence the yield of a production process are the time to accumulate a target amount of biomass, the process duration, and the specific productivity of the employed cell line. In this chapter, the contribution of the cell line, culture medium, cultivation parameters, and mode of process operation to product yield and quality are discussed.Besides mammalian cell cultures, yeasts and filamentous fungi are widely used eukaryotic expression systems for recombinant protein production. They are capable of performing the posttranslational modifications required for mAb production, although differences in protein glycosylation have to be considered. This chapter gives an overview of yeast, fungal, and higher eukaryotic species used as production hosts for full-length mAbs and antibody fragments and highlights critical cell and process engineering steps required for efficient mAb production.