Bor-Shiun Chen, Hsin-Lin Lu, Dalton Chen, and Wei-Kuang Chi* Bioengineering Department, Biologics Institute, Development Center for Biotechnology No. 101, Lane 169, Kangning St., Xizhi District, New Taipei City, 22180, Taiwan E-mail: bosiuche@dcb.org.tw; hllu9999@dcb.org.tw; dtchen@dcb.org.tw; weikchi@dcb.org.tw In the industry, biologics mass production requires the use of suspension adapted CHO cells and the best culture conditions. Development center for biotechnology (DCB) in Taiwan have adapted CHO-K1, CHO-DXB11 and CHO/dhFr- cell lines to the optimal chemically-defined medium under suspension cultivation with high VCD and low population double time. The adapted cell lines were further applied as the host for therapeutic antibody production. These suspension adapted CHO cell lines and CHO-S cells were transfected with EGFP expression plasmid for the cell transfection studies. In the stable gene expression, the IgG productivity of cell pools and single cell clones in CHO-DXB11-S1 cells was higher than that in CHO-S cells. These results implied that the in-house suspension adapted CHO-DXB11-S1 cells could be a good candidate as the producing host cell line. A series of culture strategies investigations (e.g. osmolality, feeding and epigenetic approach) on cell growth and antibody production for the potential transfected CHO-DXB11-S1 single cell clones were further carried out. These approaches affected both cell growth and monoclonal antibody expression, however not for the cell stability. The monoclonal antibody expression was improved to about 1.3 g/L from 0.9 g/L by drug selection. The antibody titer and specific productivity was further improved by 62.7% and more than 230% respectively by a culture optimization even through 60 generation of adaptive cultivation with medium S2A3. Based on these results, the optimization of culture strategies enhanced monoclonal antibody expression and achieved a material cost reduction of more than 40% and be worth further studies.

Culture strategies enhancing the suspension adapted CHO-DXB11-S1 high producing cell line expression

255th National Meeting (2018)

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