Chemical Caspase Inhibitors Enhance Cell Culture Viabilities and Protein Titer

详细信息    查看全文

• 作者：Nilou Arden ; Shin-hyung Ahn ; Wayne Vaz ; Malcolm Rhodes ; Christina Hancock ; M. Abi Abitorabi ; Michael J. Betenbaugh
• 刊名：Biotechnology Progress
• 出版年：2007
• 出版时间：April 2007
• 年：2007
• 卷：23
• 期：2
• 页码：506 - 511
• 全文大小：338K
• 年卷期：v.23,no.2(April 2007)
• ISSN：1520-6033

文摘

Mammalian cell cultures are integral to the production of therapeutic and diagnostic proteins. Acommon problem encountered in culturing these cell lines, however, is a loss in viability atlater stages of the cell culture process. In this study the effects of three newly synthesized chemicalcaspase inhibitors were investigated for their capacity to inhibit cell death. Findings show thatthese protease inhibitors were successful in prolonging cellular viabilities among anchorage-dependent CHO-K1 and HEK-293 cells lines. Cells treated with one inhibitor, 7312, performedas well or better when compared with the commercially known caspase inhibitor, zVAD.fmk.Suspension CHO cells producing an IgG were used to investigate the capacity of 7312 to improveprotein production. Treatment of cells with 7312 increased integrated cell densities by 33%with treated cells having a higher maximum cell density and higher viability. As a result,monoclonal antibody titers increased by 20% and higher in spinner flask experiments. Increasingproductivity in mammalian cell cultures has key implications for the pharmaceutical andbiotechnology sectors, which are presently focused on developing methods to enhance cellperformance in bioreactor environments.