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Establishment of a novel cell line, CHO-MK, derived from Chinese hamster ovary tissues for biologics manufacturing

中国仓鼠卵巢细胞 卵巢 细胞培养 重组DNA 毛茛 单克隆抗体 细胞生物学 生物制药 细胞生长 仓鼠 分子生物学 生物 抗体 生物化学 免疫学 遗传学 生物技术 基因
作者
Kenji Masuda,Michi Kubota,Yuto Nakazawa,Chigusa Iwama,Kazuhiko Watanabe,Naoto Ishikawa,Yumiko Tanabe,Satoru Kono,Hiroki Tanemura,Shinichi Takahashi,Tomohiro Makino,Takeshi Okumura,Takayuki Horiuchi,Koichi Nonaka,S. Murakami,Masamichi Kamihira,Takeshi Ōmasa
出处
期刊:Journal of Bioscience and Bioengineering [Elsevier]
标识
DOI:10.1016/j.jbiosc.2024.02.005
摘要

Chinese hamster ovary (CHO) cells are widely used as a host for producing recombinant therapeutic proteins due to advantages such as human-like post-translational modification, correct protein folding, higher productivity, and a proven track record in biopharmaceutical development. Much effort has been made to improve the process of recombinant protein production, in terms of its yield and productivity, using conventional CHO cell lines. However, to the best of our knowledge, no attempts have been made to acquire new CHO cell lines from Chinese hamster ovary. In this study, we established and characterized a novel CHO cell line, named CHO-MK, derived from freshly isolated Chinese hamster ovary tissues. Some immortalized cell lines were established via sub-culture derived from primary culture, one of which was selected for further development toward a unique expression system design. After adapting serum-free and suspension culture conditions, the resulting cell line exhibited a considerably shorter doubling time (approximately 10 h) than conventional CHO cell lines (approximately 20 h). Model monoclonal antibody (IgG1)-producing cells were generated, and the IgG1 concentration of fed-batch culture reached approximately 5 g/L on day 8 in a 200-L bioreactor. The cell bank of CHO-MK cells was prepared as a new host and assessed for contamination by adventitious agents, with the results indicating that it was free from any such contaminants, including infectious viruses. Taking these findings together, this study showed the potential of CHO-MK cells with a shorter doubling time/process time and enhanced productivity in biologics manufacturing.
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