Bioreactor-Based Production of Glycoproteins in Plant Cell Suspension Cultures

Recombinant glycoproteins such as monoclonal antibodies have a major impact on modern healthcare systems, e.g., as the active pharmaceutical ingredients in anticancer drugs. A specific glycan profile is often necessary to achieve certain desirable activities, such as the effector functions of an antibody, receptor binding or a sufficient serum half-life. However, many expression systems produce glycan profiles that differ substantially from the preferred form (usually the form found in humans) or produce a diverse array of glycans with a range of in vivo activities, thus necessitating laborious and costly separation and purification processes. In contrast, protein glycosylation in plant cells is much more homogeneous than other systems, with only one or two dominant forms. Additionally, these glycan profiles tend to remain stable when the process and cultivation conditions are changed, making plant cells an ideal expression system to produce recombinant glycoproteins with uniform glycan profiles in a consistent manner. This chapter describes a protocol that uses fermentations using plant cell cultures to produce glycosylated proteins using two different types of bioreactors, a classical autoclavable STR 3-L and a wave reactor.