Two-stage depth filter perfusion culture for recombinant antibody production by recombinant Chinese hamster ovary cell |
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Authors: | Joon Chul Lee Do Yun Kim Duk Jae Oh Ho Nam Chang |
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Institution: | (1) Department of Chemical and Biomolecular Engineering, KAIST, Daejeon, 305-701, Korea;(2) Department of Bioscience and Biotechnology, Sejong University, Seoul, 143-747, Korea;(3) Center for Advanced Bioseparation Technology, Inha University, Incheon, 402-750, Korea;(4) Present address: Korea Institute of Industrial Technology, Incheon, 406-840, Korea |
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Abstract: | A rCHO cell line of DUKX origin 26*-320, producing recombinant antibody against the human platelet, was cultivated in a two-stage
depth filter perfusion system (DFPS) for 20 days in order to attain high recombinant antibody concentration. The productivity
of the first stage DFPS bioreactor reached 53 times that of the batch culture in a controlled stirred tank reactor and was
showed 12.1 mg/L antibody concentration at a perfusion rate of 6.0 d−1. Glucose concentration in the first DFPS was maintained at 1.5 g/L to avoid cell damage in the perfusion culture. A second
stage DFPS system was attached to the first DFPS, which resulted in a low glucose concentration of 0.02 g/L and a high antibody
concentration of 23.9 mg/L. The two-stage depth filter perfusion culture yielded 60% higher product concentration than the
batch and 49-fold higher productivity of 69.3 mg/L/d in comparison with that (1.4 mg/L/d) in a batch system. Furthermore,
antibody concentration of the second stage was 97% higher than that of the first stage, and the antibody productivities were
comparable to that of the first stage. This two-stage DFPS system also showed potential for higher titer production of recombinant
antibody and high volumetric productivity for long-term culture of bio-pharmaceutical substances. |
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Keywords: | CHO cells perfusion culture recombinant antibody two-stage depth filter perfusion system |
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