著作: [鬼塚 正義]/⻆屋 行紀/[大政 健史]/Secretory leakage of IgG1 aggregates from recombinant Chinese hamster ovary cells/[Journal of Bioscience and Bioengineering]
(英) Secretory leakage of IgG1 aggregates from recombinant Chinese hamster ovary cells
(英) Aggregation of therapeutic antibodies is one of the most important issues to be resolved in manufacturing processes because of reduced efficacy and immunogenicity. Despite aggregation studies in vitro, little is known about the aggregation mechanism in cell culture processes. In this study, we investigated the process of aggregate formation of IgG1 antibodies during the culture of Chinese hamster ovary (CHO) cells to determine how aggregation occurs. A recombinant CHO cell line was cultivated in a bioreactor, and purified IgG1 from daily culture supernatants was analyzed by size exclusion chromatography. We found a linear correlation between the peak plots of IgG1 by-products, dimeric and aggregated IgG1, and integrated viable cell density, indicating that these by-products were secreted from CHO cells at a constant secretion rate. In addition, aggregate formation was not reproduced in pseudo-culture experiments, and the solution structures of intracellular and extracellular IgG1 aggregates were similar. These results support the concept of secretory leakage of IgG1 by-products. Secreted aggregates appeared to be in an alternatively folded state, which can pass through the protein quality control system in mammalian cells.
Journal of Bioscience and Bioengineering([日本生物工学会])
|年月日||必須||2019年 6月 初日|