Abstract
Two CHO cell clones derived from the same parental CHOBC® cell line and producing the same monoclonal antibody (BC-G, a low producing clone; BC-P, a high producing clone) were tested in four basal media in all possible combinations with three feeds (=12 conditions) in fed-batch cultures. Higher amino acid feeding did not always lead to higher mAb production. The two clones showed differences in cell physiology, metabolism and optimal medium-feed combinations. During the phase transitions of all cultures, cell metabolism showed a shift represented by lower specific consumption and production rates, except for the specific glucose consumption rate in cultures fed by Actifeed A/B. The BC-P clone fed by Actifeed A/B showed a threefold cell volume increase and an increase of the specific consumption rate of glucose in the stationary phase. Since feeding was based on glucose this resulted in accumulation of amino acids for this feed, while this did not occur for the poorer feed (EFA/B). The same feed also led to an increase of cell size for the BC-G clone, but to a lesser extent.
Highlights
Chinese Hamster Ovary (CHO) cells are the main production host for recombinant therapeutic proteins (Wurm 2004)
This study investigates the effects of different basal media and feeds on cell growth, metabolism, physiology, and monoclonal antibody (mAb) production for two differentially behaving clones derived from the same parental cell line
OptiCHO is relatively poorer whereas FortiCHO and ActiCHO-P are richer in amino acids content
Summary
Chinese Hamster Ovary (CHO) cells are the main production host for recombinant therapeutic proteins (Wurm 2004). For a fed-batch process volumetric productivity and product titer are important outputs These outputs are a function of viable cell density (VCD), specific productivity (qp), and culture longevity, which in turn are influenced by the medium and feed composition. Defined basal media and feeds are currently the standard for CHO cell fedbatch cultures. A feed is generally more concentrated than a basal medium to maximize culture volumetric productivity and product titer. Studies have shown that the composition of culture media and feeds can influence cell growth, protein productivity (Rodrigues et al 2012), gene expression (Zagari et al 2013), product quality (Costa et al 2013; Hossler et al 2009; Reinhart et al 2015), and metabolism of lactate and ammonia (Zagari et al 2013; Kyriakopoulos and Kontoravdi 2014; Luo et al 2012; Ma et al 2009)
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