Abstract
Objective
To investigate the effect of lowering culture temperature on monoclonal antibody charge variation distribution in Chinese hamster ovary cell cultures.
Results
In both batch and fed-batch cultures, lowering the culture temperature decreased the antibody acidic variant levels. The acidic variant levels (defined as variants eluting earlier than the main peak of an antibody during HPLC) at 32 °C were about 10 % lower than those at 37 °C at the end of both batch and fed-batch cultures. Additionally, lowering the culture temperature increased the lysine variant level, which further increased basic variant level. The lysine variant levels at 32 °C were about 8 % (batch culture) and 3 % (fed-batch culture) higher than those at 37 °C at the end of cultures. Real-time PCR results suggests that the decrease in carboxypeptidase B transcription level might be partially responsible for the increased lysine variant level at sub-physiological temperatures.
Conclusion
Culture temperature exhibits noticeable impact on antibody charge variation distribution, especially the acidic variants and lysine variants.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (Nos. 21406066, 21206040), the National High Technology Research and Development Program of China (863 Program) (No. 2012AA02A303), the National Science and Technology Major Project (No. 2013ZX10004003-003-003).
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Zhang, X., Sun, YT., Tang, H. et al. Culture temperature modulates monoclonal antibody charge variation distribution in Chinese hamster ovary cell cultures. Biotechnol Lett 37, 2151–2157 (2015). https://doi.org/10.1007/s10529-015-1904-3
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DOI: https://doi.org/10.1007/s10529-015-1904-3