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All-trans retinoic acid in combination with sodium butyrate enhances specific monoclonal antibody productivity in recombinant CHO cell line

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Abstract

The effects of all-trans retinoic acid (RA) and sodium butyrate (NaBu) on growth, viability and antibody production of two types of transfected Chinese hamster ovary cell lines (CHO-K1 and CHO-S) were investigated using a batch mode cell culture. By adding 0.5 mM NaBu in the CHO-K1 cell culture, the cell specific productivity (Qp) and antibody concentration increased by five- and threefold, respectively. The optimal concentration of RA was 100 nM which resulted in twofold increase in antibody production. In a combination model, RA applied at early growth phase of CHO-K1 cells followed by addition of NaBu with lowering culture temperature at the end of stationary phase resulted in two- and threefold increase in Qp and final antibody concentration, respectively. The latter strategy was also applied on suspended CHO-S cells with enhanced Qp and antibody concentration, but to a lesser extent than the CHO-K1 cells. In conclusion, our results demonstrate that the addition of RA and NaBu along with lowering the culture temperature can increase cell culture period as well as Qp and the final concentration of recombinant monoclonal antibody in both CHO-K1 and CHO-S cells without any significant change in binding affinity of the mAb.

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Acknowledgements

This work was supported partially by grants from Tarbiat Modares University and Tehran University of Medical Sciences.

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Authors and Affiliations

  1. Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran

    Mahmood Rahimi-Zarchi & Seyed Abbas Shojaosadati

  2. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Mehdi Amiri & Fazel Shokri

  3. Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

    Mahmood Jeddi-Tehrani

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  1. Mahmood Rahimi-Zarchi
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  3. Mohammad Mehdi Amiri
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Correspondence to Seyed Abbas Shojaosadati or Fazel Shokri.

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Rahimi-Zarchi, M., Shojaosadati, S.A., Amiri, M.M. et al. All-trans retinoic acid in combination with sodium butyrate enhances specific monoclonal antibody productivity in recombinant CHO cell line. Bioprocess Biosyst Eng 41, 961–971 (2018). https://doi.org/10.1007/s00449-018-1927-y

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  • DOI: https://doi.org/10.1007/s00449-018-1927-y

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