Monoclonal antibodies (mAbs) are glycoproteins that have become leading therapeutics for treating numerous cancers and chronic and inflammatory illnesses. These proteins are produced mainly in Chinese hamster ovary (CHO) cells for several advantageous reasons including scalable culture, high productivity, and suitable glycosylation characteristics. The traditional focus for improving mAb production has centered on raising antibody yields of individual batches by either increasing culture length, manipulating process conditions, or selecting higher productivity clones for commercial production. Despite the stunning progress and improvements to antibody yield in the last twenty years, a continuing challenge is to identify process conditions that balance maximum titer with optimal critical quality attributes (CQAs).<br/>                Glycosylation is a CQA that impacts antibody stability, serum half-life, and effector functions (ADCC & CDC). The pathway for antibody glycosylation is non-template-directed and heterogeneous process, with nearly a dozen enzymes across both the ER and the Golgi apparatus participating in protein modification. Many improvements to instrumentation and methods have enabled faster and higher resolution glycosylation analysis, but mechanistic insights about glycan variations between cell lines, media formulations, and process conditions still remain scarce. Here, we utilize a design of experiments (DoE) approach to determine how different media supplementation dynamically impact glycosylation throughout a batch process of antibody-producing CHO cells. Glycan profiles will be compared with metabolic information throughout the culture’s duration to determine how nutrient availability contributed to overall glycosylation, and factorial analysis will be shared to assess effects and statistical impact of each supplement on titer, [metabolites], and glycan profile.<br/>

Effects of media supplementation on CHO-produced antibody glycosylation: Dynamic changes in glycoform profiles throughout batch culture

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.