Dissecting cell death pathways in fed-batch bioreactors

David A Mentlak, John Raven, Tessa Moses, Fraser Massie, Nicholas Barber, Robyn Hoare, Graeme Burton, Alison Young, Leon P Pybus, Susan Rosser, Robert J White, Daniel Ungar, Nia J Bryant

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Chinese hamster ovary (CHO) cells are widely used for production of biologics including therapeutic monoclonal antibodies. Cell death in CHO cells is a significant factor in biopharmaceutical production, impacting both product yield and quality. Apoptosis has previously been described as the major form of cell death occurring in CHO cells in bioreactors. However, these studies were undertaken when less was known about non-apoptotic cell death pathways. Here, we report the occurrence of non-apoptotic cell death in an industrial antibody-producing CHO cell line during fed-batch culture. Under standard conditions, crucial markers of apoptosis were not observed despite a decrease in viability towards the end of the culture; only by increasing stress within the system did we observe caspase activation indicative of apoptosis. In contrast, markers of parthanatos and ferroptosis were observed during standard fed-batch culture, indicating that these non-apoptotic cell death pathways contribute to viability loss under these conditions. These findings pave the way for targeting non-conventional cell death pathways to improve viability and biologic production in CHO cells.

Original languageEnglish
Article number2300257
Number of pages12
JournalBiotechnology journal
Issue number1
Early online date7 Dec 2023
Publication statusPublished - 14 Jan 2024

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© 2023 The Authors.

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