Heat shock protein 27 overexpression in CHO cells modulates apoptosis pathways and delays activation of caspases to improve recombinant monoclonal antibody titre in fed-batch bioreactors

Biotechnology Journal
Janice TanSay Kong Ng

Abstract

CHO cells are major production hosts for recombinant biologics including the rapidly expanding recombinant monoclonal antibodies (mAbs). Heat shock protein 27 (HSP27) expression was observed to be down-regulated towards the late-exponential and stationary phase of CHO fed-batch bioreactor cultures, whereas HSP27 was found to be highly expressed in human pathological cells and reported to have anti-apoptotic functions. These phenotypes suggest that overexpression of HSP27 is a potential cell line engineering strategy for improving robustness of CHO cells. In this work, HSP27 was stably overexpressed in CHO cells producing recombinant mAb and the effects of HSP27 on cell growth, volumetric production titer and product quality were assessed. Concomitantly, HSP27 anti-apoptosis functions in CHO cells were investigated. Stably transfected clones cultured in fed-batch bioreactors displayed 2.2-fold higher peak viable cell density, delayed loss of culture viability by two days and 2.3-fold increase in mAb titer without affecting the N-glycosylation profile, as compared to clones stably transfected with the vector backbone. Co-immunoprecipitation studies revealed HSP27 interactions with Akt, pro-caspase 3 and Daxx and caspase activity ...Continue Reading

References

Nov 13, 1998·Science·M H CardoneJ C Reed
Dec 2, 1999·Genes & Development·S R DattaM E Greenberg
Sep 12, 2000·Nature Cell Biology·J M BrueyC Garrido
Sep 26, 2000·Molecular and Cellular Biology·S J CharetteJ Landry
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jan 3, 2003·Apoptosis : an International Journal on Programmed Cell Death·C G ConcannonA Samali
Jan 13, 2006·Biochemical and Biophysical Research Communications·M DerouaziF M Wurm
May 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yong Zhang, Xun Shen
Feb 13, 2008·Journal of Cellular and Molecular Medicine·D LanneauC Garrido
Nov 4, 2008·Biotechnology and Bioengineering·Janet ChusainowMiranda G S Yap
Jun 26, 2009·Trends in Pharmacological Sciences·Royston Jefferis
Mar 28, 2012·The International Journal of Biochemistry & Cell Biology·C GarridoH H Kampinga
Jan 11, 2014·Nature Biotechnology·Rob Saurabh Aggarwal
Jul 9, 2014·Nature Biotechnology·Stacy Lawrence, Riku Lahteenmaki

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Citations

Nov 3, 2015·Biotechnology Advances·Simon FischerKerstin Otte
Jan 14, 2020·Biotechnology and Bioengineering·Matthew N HenryVerónica S Martínez
Sep 1, 2020·Biotechnology and Bioengineering·Camila A OrellanaEsteban Marcellin
Sep 2, 2017·Biotechnology Journal·Beate BeyerNico Lingg
Jul 28, 2019·Nucleic Acids Research·Iqbal Mahmud, Daiqing Liao

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