The CHO cell line as a potentially safer host for cetuximab therapeutic antibody production than the Sp2/0 cell line

被引：0
作者：
Bartusik-Czubek E.E. [1 ]
Czubek B.M. [1 ]
Toboła P.E. [1 ]
Lonkwic K.M. [1 ]
Miłek P.P. [1 ]
Grzyb O.H. [1 ]
Balcerek J.A. [1 ]
Pietrucha T. [2 ]
Jaros S. [1 ]
机构：
[1] Mabion S.A. Scientific-Industrial Complex of Medicinal Biotechnology, Langiewicza 60 Street, Konstantynów Łódzki
[2] Medical University of Lodz, Zeligowskiego 7/9 Street, Łódź
来源：
International Journal of Biotechnology | 2023年 / 14卷 / 04期
关键词：
antibodies; antibody production; bioanalysis; biosimilars; biotechnology; cell lines; cetuximab; Chinese hamster ovary cell line; glycoproteins; glycosylation;
D O I：
10.1504/IJBT.2023.138705
中图分类号：
学科分类号：
摘要：
The host cell line influences the quality of the recombinant protein produced within it. In the case of monoclonal antibodies, the most frequently chosen hosts are hamster- and mouse-derived cell lines. However, the glycosylation profile of the mAbs generated using these cell lines is expected to be different. In this study, we used the cetuximab protein obtained from the Sp2/0 and CHO cell lines to analyse the content of fucosylated and non-fucosylated glycoforms, as well as structures containing N-glycolylneuraminic acid, N-acetylneuraminic acid and Gal-Gal structures. Our results confirm literature data suggesting a higher level of fucosylated glycoforms and a higher level of N-acetylneuraminic acid in CHO- over Sp2/0-derived cetuximab. We also confirm the lack of Gal-Gal structures in the CHO-derived antibody. Moreover, we have demonstrated the Sp2/0- and CHO-derived IgG may have a comparable non-fucosylated glycoforms content. This is a significant find, since non-fucosylated species are the triggers of the biological activities of many antibodies. Copyright © 2023 Inderscience Enterprises Ltd.
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页码：277 / 292
页数：15
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共 27 条
  • [1] Ayoub D., Jabs W., Resemann A., Evers W., Evans C., Main L., Et al., Correct primary structure assessment and extensive glyco-profiling of cetuximab by a combination of intact, middle-up, middle-down and bottom-up ESI and MALDI mass spectrometry techniques, mAbs, 5, 5, pp. 699-710, (2013)
  • [2] Bartusik-Czubek E., Tobola P., Czubek B., Bednarek M., Balcerek J., Pietrucha T., Et al., Modeling of the biological activity of monoclonal antibodies based on the glycosylation profile, Journal of Pharmaceutical Sciences, 110, 4, pp. 1661-1667, (2021)
  • [3] Blick S.K.A., Scott L.J., Cetuximab. A review of its use in squamous cell carcinoma of the head and neck and metastatic colorectal cancer, Drugs, 67, 17, pp. 2585-2607, (2007)
  • [4] Brand T.M., Iida M., Wheeler D.L., Molecular mechanism of resistance to the EGFR monoclonal antibody cetuximab, Cancer Biology & Therapy, 11, 9, pp. 777-792, (2011)
  • [5] Choi P., Meyerson M., Targeted genomic rearrangements using CRISPR/Cas technology, Nature Communications, 5, (2014)
  • [6] Chung C.H., Mirakhur B., Chan E., Le Q.T., Berlin J., Morse M., Et al., Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1, 3-galactose, The New England Journal of Medicine, 358, 11, pp. 1109-1117, (2008)
  • [7] Ghaderi D., Taylor R.E., Padler-Karavani V., Diaz S., Varki A., Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins, Nature Biotechnology, 28, 8, pp. 863-867, (2010)
  • [8] Goh J.B., Ng S.K., Impact of host cell line choice on glycan profile, Critical Reviews in Biotechnology, 38, 6, pp. 851-867, (2017)
  • [9] Gomes A.R., Byregowda S.M., Veeregowda B.M., Balamurugan V., An overview of heterologous expression host systems for the production of recombinant proteins, Advances in Animal and Veterinary Sciences, 4, 4, pp. 346-356, (2016)
  • [10] Hmiel L.K., Brorson K.A., Boyne M.T., Post-translational structural modifications of immunoglobulin G and their effect on biological activity, Analytical and Bioanalytical Chemistry, 407, 1, pp. 79-94, (2015)
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