Abstract
Purpose: Chinese Hamster Ovary (CHO) cells are currently the leading hosts for biosimilar Immunoglobulin G (IgG) production in the biopharmaceutical industry. Most eukaryotic proteins are glycosylated, and charge variants affect both the in vivo and in vitro properties of monoclonal antibodies (mAb). Adjusting the N-glycosylation patterns and charge variants while achieving high antibody titer is a production challenge. In this study, the effects of feed type and strategy on cell growth, product titer, glycosylation and charge variation were investigated using different CHO clones producing different IgG mAbs. Methods: Cultivated CHO cells were supplemented with different feeding schemes, under fed-batch productions of 14 days. Screenings were conducted in spin-tubes and further investigated in 3L bioreactor systems. Results: Change in feed strategy decreased productivities by 10.4% (P < 0.05), while it increased non-fucosylated glycoforms by 33.3% and enhanced galactosylation up to 3-folds. Basic variants were observed to increase 2.5 folds. Conclusion: These remarkable alterations are of great importance in terms of mAb quality, in a manufacturing point of view, as they provide modulation of efficacy and safety. This reveals that feed strategy is a major driving force that significantly impacts culture longevity, galactosylated glycoforms, high-mannose glycan contents and charge variants.
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