Imperial College London
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Professor Cleo Kontoravdi

Faculty of Engineering, Department of Chemical Engineering

Professor of Biological Systems Engineering
 
 
 
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Contact

 

+44 (0)20 7594 6655cleo.kontoravdi98 Website

 
 
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Location

 

310ACE ExtensionSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Goey:2017:10.1002/bit.26437,
author = {Goey, CH and Tsang, J and Bell, D and Kontoravdi, C},
doi = {10.1002/bit.26437},
journal = {Biotechnology and Bioengineering},
pages = {2771--2781},
title = {Cascading effect in bioprocessing – the impact of mild hypothermia on CHO cell behavior and host cell protein composition},
url = {http://dx.doi.org/10.1002/bit.26437},
volume = {114},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - A major challenge in downstream purification of monoclonal antibodies (mAb) is the removal of host cell proteins (HCPs). Previous studies have shown that cell culture decisions significantly impact the HCP content at harvest. However, it is currently unclear how process conditions affect physiological changes in the host cell population, and how these changes, in turn, cascade down to change the HCP profile. We examined how temperature downshift (TDS) to mild hypothermia affects key upstream performance indicators, i.e. antibody titre, HCP concentration and HCP species, across the cell culture decline phase and at harvest through the lens of changes in cellular behaviour. Mild hypothermic conditions introduced on day 5 of fed-batch Chinese hamster ovary (CHO) cell bioreactors resulted in a lower cell proliferation rate but larger percentages of healthier cells across the cell culture decline phase compared to bioreactors maintained at standard physiological temperature. Moreover, the onset of apoptosis was less evident in mild hypothermic cultures. Consequently, mild hypothermic cultures took an extra five days to reach an integral viable cell concentration (IVCC) and antibody yield similar to that of the control at standard physiological temperature. When cell viability dropped below 80%, mild hypothermic cell cultures had a reduced variety of HCP species by 36%, including approximately 44% and 27% lower proteases and chaperones, respectively, despite having similar HCP concentration. This study suggests that TDS may be a good strategy to provide cleaner downstream feedstocks by reducing the variety of HCPs and to maintain product integrity by reducing the number of proteases and chaperones.
AU  - Goey,CH
AU  - Tsang,J
AU  - Bell,D
AU  - Kontoravdi,C
DO  - 10.1002/bit.26437
EP  - 2781
PY  - 2017///
SN  - 0006-3592
SP  - 2771
TI  - Cascading effect in bioprocessing – the impact of mild hypothermia on CHO cell behavior and host cell protein composition
T2  - Biotechnology and Bioengineering
UR  - http://dx.doi.org/10.1002/bit.26437
UR  - https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.26437
UR  - http://hdl.handle.net/10044/1/50466
VL  - 114
ER  -
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