Application Two Disposable Bioreactor Systems for the Production of hCTLA4Ig in Transgenic Rice Cell Cultures

초록

Plant cell culture has been regarded as a potential alternative production system for biopharmaceuticals. There are few studies regarding their suitability for the production of pharmaceutical proteins in transgenic plant cell cultures. Requirements of simplicity, safety and flexibility for bioreactors in the modern pharmaceutical industry have resulted in the increased use of disposable bioreactors in both R&D and biomanufacturing. In this study, two types of disposable bioreactors were compared with 5-L stirred tank bioreactor system for cell growth and the production of recombinant hCTLA4Ig using transgenic rice cell cultures. Modified wave-mixed bag with a fritted sparger and an airlift disposable bioreactor were used as disposable systems. In both bioreactor systems, fed-batch cultures were performed for the efficient production of hCTLA4Ig by feeding concentrated amino acids. Dissolved oxygen level was controlled at 30% by adding pure oxygen with solenoid valve during the run. The results from wave-mixed, airlift disposable bioreactor and 5-L STR showed similar maximum cell density (12.6, 11.9, 12.2 gDCW/L), doubling time (5.03, 4.84, 4.62 day) and maximum hCTLA4Ig concentration (44.5, 43.7, 48.5 mg/L), respectively. These results will be useful for further optimization and scale-up studies of disposable bioreactor systems for plant cell cultures.