UBC Theses and Dissertations

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UBC Theses and Dissertations

Autophagy inhibition and hypertonicity increased monoclonal antibody production in chinese hamster ovary fed-batch cultures Nasseri, Sayyed Soroush


Biopharmaceuticals have improved the treatment of many diseases such as cancers and strokes, with much reduced adverse effects. However, high prices pose a major challenge to their widespread application. Improvements to cell culture processes can ease this burden, and facilitate the access to high quality biological medications for increasing sections of world society. This thesis addresses two methods to increase the productivity of the Chinese Hamster Ovary (CHO) cells expressing monoclonal antibodies using either autophagy inhibition or hypertonicity. Autophagy is a cellular process whereby intracellular components are degraded in response to nutrient limitations and other stresses. It has previously been shown that 3-methyladenine (3-MA) inhibition of autophagy can increase fed-batch tissue plasminogen activator production. This thesis investigated autophagy inhibition in fed-batch cultures of CHO cells producing monoclonal antibodies (MAb). Hypertonicity in mammalian cell cultures has also been shown to increase the MAb productivity of mammalian cell cultures. By investigating the timing and dose of 3-MA, more than two-fold increases in cell specific productivity and an up to two-fold increase in total MAb were obtained. Hypertonic conditions can similarly increase the productivity of fed-batch cultures by more than two-fold. The combination of these two approaches, however, did not result in any increase in productivity. Neither autophagy inhibition nor hypertonicity significantly changed the glycan profiles of the MAb product.

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