Using simple models to describe the kinetics of growth, glucose consumption, and monoclonal antibody formation in naive and infliximab producer CHO cells

摘要: Despite their practical and commercial relevance, there are few reports on the kinetics of growth production Chinese hamster ovary (CHO) cells—the most frequently used host for industrial therapeutic proteins. We characterize cell growth, substrate consumption, product formation in naive monoclonal antibody (mAb) producing recombinant CHO cells. Culture experiments were performed 125 mL shake flasks culture medium (CD Opti CHO™ Invitrogen, Carlsbad, CA, USA) diluted to different glucose concentrations (1.2–4.8 g/L). The time evolution cell, glucose, lactic acid concentration was monitored a daily basis mAb-producing cultures counterparts. series differentiated calculate corresponding kinetic rates (rx = d[X]/dt; rs = d[S]/dt; rp = d[mAb]/dt). Results showed that these lines could be modeled by Monod-like if threshold value [S]t = 0.58 g/L (for cells) [S]t = 0.96 g/L cells), below which is not observed, considered. A set values μmax, Ks determined cultured at 33 37 °C. yield coefficient (Yx/s) observed function concentration, with range 0.27–1.08 × 107 cell/mL 0.72–2.79 × 106 cells/mL cultures, respectively. mAb can described Luedeking–Piret model (d[mAb]/dt = αd[X]/dt + β[X]) α = 7.65 × 10−7 µg/cell β = 7.68 × 10−8 µg/cell/h conducted batch-agitated batch instrumented bioreactors operated fed-batch mode.