Lipidomics of CHO Cell Bioprocessing: Relation to Cell Growth and Specific Productivity of a Monoclonal Antibody

摘要

As the demand for biological therapeutic proteins rises, there is an increasing need for robust and highly efficient bioprocesses, specifically, maximizing protein production by controlling the cellular nutritional and metabolic needs. A comprehensive lipidomics analysis has been performed, for the first time, over the time course of CHO cells producing an IgG1 monoclonal antibody (mAb) with fed batch 5 L bioreactors. The dynamic nature and importance of the CHO lipidome, especially on cellular growth and specific productivity, is demonstrated. A robust LC-MS method using positive and negative mode ESI was developed for lipid identification and quantitation of 377 unique lipids. The analysis revealed large changes in lipid features between the different days in bioprocessing including accumulation of triacylglycerol (TG) and lysophospholipid species with depletion of diacylglycerol (DG) species. Exploring pathway analysis where the lipid data was combined with polar metabolites and transcriptomics (RNA sequencing) revealed differences in lipid metabolism between the various stages of cellular growth and highlighted the role of key features of lipid metabolism on cell growth and specific productivity. The study demonstrates the importance of lipidomics in the expanding role of Omics methodologies in gaining insight into cellular behavior during protein production in a fed batch bioprocess.