Effect of culture temperature on TNFR-Fc productivity in recombinant glutamine synthetase-chinese hamster ovary cells.
Lowering the culture temperature is often useful to improve the production of many recombinant proteins in Chinese hamster ovary (CHO) cells. Batch cultivation of GS-CHO cells expressing TNFR-Fc antibody was therefore carried out at 30, 33.5 and 37 degrees C. TNFR-Fc productivity, q(TNFR-Fc), increased as culture temperature decreased; and the maximum q(TNFR-Fc) was 20 mg/(10(9) cells.day) at 30 degrees C which was three times that at 37 degrees C. Increasing the viable cell density (VCD) to above 2.2 x 10(6) cells/ml, however, decreased the q(TNFR-Fc) at 30 degrees C, which was due to a reduction in transcription of the TNFR-Fc gene. Taken together, lowering temperature can improve q(TNFR-Fc) but the negative effect of increasing VCD compromises this effect. Further process development addressing the issue of cell density-dependent TNFR-Fc productivity is therefore needed.
The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, MeiLong Road 130, Shanghai 200237, China.
Li
L
Fan
Liang
L
Zhao
Zhaoyang
Z
Ye
Yating
Y
Sun
Tianci
T
Kou
Yan
Y
Zhou
Wen-Song
WS
Tan
D000818:Animals; D001709:Biotechnology / Q000379:methods*; D016466:CHO Cells; D018929:Cell Culture Techniques; D006224:Cricetinae; D003412:Cricetulus; D000068800:Etanercept; D005974:Glutamate-Ammonia Ligase / Q000172:deficiency; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D005974:Glutamate-Ammonia Ligase; D000068800:Etanercept