The Formidable Challenge of Controlling High Mannose-Type N-Glycans in Therapeutic mAbs.

The clinical efficacy and safety of therapeutic monoclonal antibodies (mAbs) are significantly affected by their Fc-glycosylation profile. High mannose-type N-glycans (HM) affect efficacy (in terms of antibody-dependent cell cytotoxicity), pharmacokinetics, and stability. While in endogenous IgGs the HM levels are very low, they are significantly higher in marketed therapeutic mAbs. In order to meet the demands for late-phase clinical trial and market supply, process intensification is required. Since glycosylation profiles are sensitive to process variations and changes, controlling HM levels in robust manufacturing processes presents a formidable challenge and requires a thorough understanding of the cellular processes as well as the biotechnical aspects that govern the production of HM glycans.