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Chapter 12 : Mammalian Cell Culture for Biopharmaceutical Production

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Abstract:

This chapter summarizes the recent developments of biopharmaceutical production using mammalian cell culture, and focuses on monoclonal antibodies (MAbs), which is the most dominant and most rapidly developing sector in the biopharmaceutical industry, and its large-scale production the most established. Two expression vector systems dominate antibody production in mammalian cell culture, one based on dihydrofolate reductase (DHFR) genes and the other on glutamine synthetase (GS) genes. To improve outgrowth and transfection efficiency, transfection is predominantly performed in serum-containing media, but using host or parental cell lines preadapted to grow in suspension and serum-free media reduces adaptation times and increases the likelihood of reaching high cell densities and high product yields in serum-free suspension culture. Apoptosis is induced by various chronic insults and is mediated by several mechanisms. Various strategies were implemented to inhibit apoptosis, including the prevention of nutrient limitation by fed-batch operation, which can delay the onset and extent of apoptosis, and engineering of resistance into the cell line, such as the regulatory Bcl-2 family of proteins, which affect the activation of apoptosis pathways in cells. Novel technologies such as enhanced expression systems, automated screening methods, cell line engineering, improved process monitoring, and disposable apparatuses are leading to more productive and efficient production of biopharmaceuticals by mammalian cell culture.

Citation: Zhang J. 2010. Mammalian Cell Culture for Biopharmaceutical Production, p 157-178. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch12

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Tables

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TABLE 1

FDA-approved monoclonal antibody products

Citation: Zhang J. 2010. Mammalian Cell Culture for Biopharmaceutical Production, p 157-178. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch12

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