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Review
. 2016 Apr;100(8):3451-61.
doi: 10.1007/s00253-016-7388-9. Epub 2016 Mar 3.

Advances in recombinant antibody manufacturing

Renate Kunert  1 , David Reinhart  2
Affiliations
Review

Advances in recombinant antibody manufacturing

Renate Kunert et al. Appl Microbiol Biotechnol. 2016 Apr.

Abstract

Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. In this review, we have highlighted several key milestones that have contributed to the success of CHO cells from the beginning of their use for monoclonal antibody (mAb) expression until today. The main factors influencing the yield of a production process are the time to accumulate a desired amount of biomass, the process duration, and the specific productivity. By comparing maximum cell densities and specific growth rates of various expression systems, we have emphasized the limiting parameters of different cellular systems and comprehensively described scientific approaches and techniques to improve host cell lines. Besides the quantitative evaluation of current systems, the quality-determining properties of a host cell line, namely post-translational modifications, were analyzed and compared to naturally occurring polyclonal immunoglobulin fractions from human plasma. In summary, numerous different expression systems for mAbs are available and also under scientific investigation. However, CHO cells are the most frequently investigated cell lines and remain the workhorse for mAb production until today.

Keywords: Chinese hamster ovary (CHO); Human embryonic kidney (HEK); Mammalian expression systems; Monoclonal antibody (mAb) manufacturing; NS0; Optimization strategies; PER.C6; Process advances.

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Figures

Fig. 1
Fig. 1
Calculated exponential growth of P. pastoris and two CHO cell lines. For P. pastoris, a starting WCW of 0.4 g/L (20 × 106 cells/mL) and a μ of 0.15/h were assumed (full line), CHO cell lines were inoculated with 0.3 × 106 cells/mL (0.6 g/L) and a μ of 0.7/day (0.029/h) (dashed line), and 0.6/day (0.025/h) (chain line) was estimated
Fig. 2
Fig. 2
Typical cell and product concentrations achieved due to process improvements in the past three decades
Fig. 3
Fig. 3
Score of scientific publications in PubMed (US National Library of Medicine) using diverse popular cell lines for recombinant protein expression in the last 10 years as well as total results
See this image and copyright information in PMC

References

    1. Altamirano C, Illanes A, Casablancas A, Gámez X, Cairó JJ, Gòdia C. Analysis of CHO cells metabolic redistribution in a glutamate-based defined medium in continuous culture. Biotechnol Prog. 2001;17:1032–1041. doi: 10.1021/bp0100981. - DOI - PubMed
    1. Altamirano C, Paredes C, Illanes A, Cairó JJ, Gòdia F. Strategies for fed-batch cultivation of t-PA producing CHO cells: substitution of glucose and glutamine and rational design of culture medium. J Biotechnol. 2004;110:171–179. doi: 10.1016/j.jbiotec.2004.02.004. - DOI - PubMed
    1. Arden N, Ahn SH, Vaz W, Rhodes M, Hancock C, Abitorabi MA, Betenbaugh MJ. Chemical caspase inhibitors enhance cell culture viabilities and protein titer. Biotechnol Prog. 2007;23:506–511. doi: 10.1021/bp060222m. - DOI - PubMed
    1. Benton T, Chen T, McEntee M, Fox B, King D, Crombie R, Thomas TC, Bebbington C. The use of UCOE vectors in combination with a preadapted serum free, suspension cell line allows for rapid production of large quantities of protein. Cytotechnology. 2002;38:43–46. doi: 10.1023/A:1021141712344. - DOI - PMC - PubMed
    1. Borth N, Mattanovich D, Kunert R, Katinger H. Effect of increased expression of protein disulfide isomerase and heavy chain binding protein on antibody secretion in a recombinant CHO cell line. Biotechnol Prog. 2005;21:106–111. doi: 10.1021/bp0498241. - DOI - PubMed

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