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  • Generation of reference cel...
    Cordova, Lauren T.; Dahodwala, Hussain; Elliott, Kathryn S.; Baik, Jongyoun; Odenewelder, Daniel C.; Nmagu, Douglas; Skelton, Bradley A.; Uy, Lisa; Klaubert, Stephanie R.; Synoground, Benjamin F.; Chitwood, Dylan G.; Dhara, Venkata Gayatri; Naik, Harnish Mukesh; Morris, Caitlin S.; Yoon, Seongkyu; Betenbaugh, Michael; Coffman, Jon; Swartzwelder, Frank; Gillmeister, Michael P.; Harcum, Sarah W.; Lee, Kelvin H.

    Biotechnology and bioengineering, March 2023, 2023-03-00, 20230301, Letnik: 120, Številka: 3
    Journal Article

    Due to the favorable attributes of Chinese hamster ovary (CHO) cells for therapeutic proteins and antibodies biomanufacturing, companies generate proprietary cells with desirable phenotypes. One key attribute is the ability to stably express multi‐gram per liter titers in chemically defined media. Cell, media, and feed diversity has limited community efforts to translate knowledge. Moreover, academic, and nonprofit researchers generally cannot study “industrially relevant” CHO cells due to limited public availability, and the time and knowledge required to generate such cells. To address these issues, a university‐industrial consortium (Advanced Mammalian Biomanufacturing Innovation Center, AMBIC) has acquired two CHO “reference cell lines” from different lineages that express monoclonal antibodies. These reference cell lines have relevant production titers, key performance outcomes confirmed by multiple laboratories, and a detailed technology transfer protocol. In commercial media, titers over 2 g/L are reached. Fed‐batch cultivation data from shake flask and scaled‐down bioreactors is presented. Using productivity as the primary attribute, two academic sites aligned with tight reproducibility at each site. Further, a chemically defined media formulation was developed and evaluated in parallel to the commercial media. The goal of this work is to provide a universal, industrially relevant CHO culture platform to accelerate biomanufacturing innovation. In this work, Cordova and coauthors present a CHO platform process using non‐proprietary cells, protocols, and chemically‐defined growth media and feeds with industrially‐relevant performance. The performance of the system was tested at two independent sites for growth in shake flasks and scale‐down bioreactors. Perhaps was comparable across the sites and conditions tested.