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Biomanufacturing

Biomanufacturing - Poster Session E

Poster M13 - ENHANCING MONOCLONAL ANTIBODY PRODUCTION THROUGH TARGETED METABOLIC ENGINEERING OF INDUSTRIAL CHO CELLS

Saturday, October 26, 2024
10:00 AM – 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Since 1986, more than 150 monoclonal antibody (mAb) therapies have been approved to treat autoimmune disorders, cancer, and other diseases. This has resulted in an increased demand for biopharmaceuticals produced from mammalian cell culture processes. To meet market demand, increasing mAb titers and cell-specific productivity (qP) is necessary to achieve a more cost-effective product and, in turn, decrease production costs. Chinese hamster ovary (CHO) host cells are used to produce about 80% of mAbs approved on the market. Our lab has previously shown that high-producing CHO cell lines exhibit elevated metabolic activity in the mitochondrial TCA cycle.

Materials and

Methods:  In particular, overexpressing an endogenous regulator that promotes mitochondrial metabolism increased mAb titer and qP but also attenuated cell growth compared to the parental line. This study aims to engineer CHO metabolism to promote mitochondrial respiration and TCA cycle flux specifically during the stationary phase, in order to minimize negative impacts on culture growth during exponential phase. We hypothesize that leveraging the endogenous regulator's expression by using an inducible promoter will maximize mAb production while mitigating negative impacts in cell growth

Results, Conclusions, and Discussions: Through transfected inducible pool screening, an average qP of approximately 10 pg/cell/mL was observed among mini pools. However, four mini pools exhibited qP values up to two times higher than the average. A key objective of this study is to showcase the utility of host cell engineering in enhancing the metabolic efficiency of mammalian cell lines used in biomanufacturing processes.

Acknowledgements (Optional):