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, qTNFR-Fc, increased as culture temperature decreased; and the maximum qTNFR-Fc was 20 mg/(10(6) cells/ml) 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 qTNFR-Fc at 30 degrees C, which was due to a reduction in transcription of the TNFR-Fc gene. Taken together, lowering temperature can improve qTNFR-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.