Yves Durocher
National Research Council, Canada
Title: Production of sialylated monoclonal antibody in CHO cells
Biography
Biography: Yves Durocher
Abstract
IgGs that possess Fc-glycans with terminal sialic acid (SA) are thought to be responsible for the anti-inflammatory properties of intravenous immunoglobulins (IVIGs) through a mechanism that is still unclear. The impact of this sialylation on IgG’s effector functions (ADCC and CDC) also remains to be elucidated. To better understand the biological impact of IgG sialylation, there is a need to produce recombinant IgGs with well characterized and more homogeneous glycan structures. The type of SA (NANA or NGNA), the nature of its linkage with the galactose residue (alpha-2,3 or alpha-2,6) or the number of glycan antennae being sialylated, may vary according to the IgG subtype, the host cell in which it is expressed and the cell culture environment. In this study, we show that the a 2,6-sialylation of IgG1’s Fc domain can be efficiently achieved by the transient co-expression of the human beta 1,4-galactosyltransferase-1 (GT) and 2,6-sialyltransferase-1 (ST6) in CHO cells. The process allows for the production of milligram amounts of human-like sialylated monoclonal antibody within two weeks. The impact of this sialylation on IgG1 binding to FcγRIIIa is also presented.
