Research Article
Year 2022,
, 6 - 15, 01.01.2022
Abstract
References
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- Reference19. Zhang X, Tang H, Sun YT, Liu X, Tan WS, Fan L. Elucidating the effects of arginine and lysine on a monoclonal antibody C-terminal lysine variation in CHO cell cultures. Appl Microbiol Biotechnol 2015; 99(16):6643–52.
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Evaluation of Feed Strategy for High Quality Biosimilar IgG Production in CHO Cell Fed-batch Process
Abstract
Purpose: Chinese Hamster Ovary (CHO) cells are currently the leading hosts for biosimilar Immunoglobulin G (IgG) production in the biopharmaceutical industry. Most eukaryotic proteins are glycosylated, and charge variants affect both the in vivo and in vitro properties of monoclonal antibodies (mAb). Adjusting the N-glycosylation patterns and charge variants while achieving high antibody titer is a production challenge. In this study, the effects of feed type and strategy on cell growth, product titer, glycosylation and charge variation were investigated using different CHO clones producing different IgG mAbs.
Methods: Cultivated CHO cells were supplemented with different feeding schemes, under fed-batch productions of 14 days. Screenings were conducted in spin-tubes and further investigated in 3L bioreactor systems.
Results: Change in feed strategy decreased productivities by 10.4% (P < 0.05), while it increased non-fucosylated glycoforms by 33.3% and enhanced galactosylation up to 3-folds. Basic variants were observed to increase 2.5 folds.
Conclusion: These remarkable alterations are of great importance in terms of mAb quality, in a manufacturing point of view, as they provide modulation of efficacy and safety. This reveals that feed strategy is a major driving force that significantly impacts culture longevity, galactosylated glycoforms, high-mannose glycan contents and charge variants.
References
- Reference1. Del Val IJ, Kontoravdi C, Nagy JM. Towards the implementation of quality by design to the production of therapeutic monoclonal antibodies with desired glycosylation patterns. Biotechnol Prog 2010; 26(6):1505–27.
- Reference2. Boune S, Hu P, Epstein AL, Khawli LA. Principles of N-Linked Glycosylation Variations of IgG-Based Therapeutics: Pharmacokinetic and Functional Considerations. Antibodies 2020; 9(2):22.
- Reference3. Pacis E, Yu M, Autsen J, Bayer R, Li F. Effects of cell culture conditions on antibody N-linked glycosylation-what affects high mannose 5 glycoform. Biotechnol Bioeng 2011; 108(10):2348–58.
- Reference4. Wong DCF, Wong NSC, Goh JSY, May LM, Yap MGS. Profiling of N-glycosylation gene expression in CHO cell fed-batch cultures. Biotechnol Bioeng 2010; 107(3):516–28.
- Reference5. Kochanowski N, Blanchard F, Cacan R, Chirat F, Guedon E, Marc A, et al. Influence of intracellular nucleotide and nucleotide sugar contents on recombinant interferon-γ glycosylation during batch and fed-batch cultures of CHO cells. Biotechnol Bioeng 2008; 100(4):721–33.
- Reference6. Khawli LA, Goswami S, Hutchinson R, Kwong ZW, Yang J, Wang X, et al. Charge variants in IgG1: Isolation, characterization, in vitro binding properties and pharmacokinetics in rats. MAbs 2010; 2(6):613–24.
- Reference7. Takagi Y, Kikuchi T, Wada R, Omasa T. The enhancement of antibody concentration and achievement of high cell density CHO cell cultivation by adding nucleoside. Cytotechnology 2017; 69(3):511–21.
- Reference8. Xu J, Rehmann MS, Xu X, Huang C, Tian J, Qian NX, et al. Improving titer while maintaining quality of final formulated drug substance via optimization of CHO cell culture conditions in low-iron chemically defined media. MAbs 2018; 10(3):488–99.
- Reference9. Rekena A, Livkisa D, Loca D. Factors affecting chinese hamster ovary cell proliferation and viability. Vide Tehnol Resur - Environ Technol Resour 2019; 1:145–248.
- Reference10. Dorai H, Yun SK, Ellis D, Kinney CA, Lin C, Jan D, et al. Expression of anti-apoptosis genes alters lactate metabolism of Chinese Hamster ovary cells in culture. Biotechnol Bioeng 2009; 103(3):592–608.
- Reference11. Pan X, Streefland M, Dalm C, Wijffels RH, Martens DE. Selection of chemically defined media for CHO cell fed-batch culture processes. Cytotechnology 2017; 69 (1): 39–56.
- Reference12. Yoon SK, Choi SL, Song JY, Lee GM. Effect of culture pH on erythropoietin production by Chinese hamster ovary cells grown in suspension at 32.5 and 37.0°C. Biotechnol Bioeng 2004; 89(3):345–56.
- Reference13. Zhu J. Mammalian cell protein expression for biopharmaceutical production. Biotechnol Adv 2012; 30(5):1158–70.
- Reference14. Wlaschin KF, Hu WS. Fedbatch culture and dynamic nutrient feeding. Vol. 101, Advances in Biochemical Engineering/Biotechnology 2006; p. 43–74.
- Reference15. Fan Y, Jimenez Del Val I, Müller C, Wagtberg Sen J, Rasmussen SK, Kontoravdi C, et al. Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation. Biotechnol Bioeng 2014; 112(3):521–35.
- Reference16. Du Z, Treiber D, Mccarter JD, Fomina-Yadlin D, Saleem RA, Mccoy RE, et al. Use of a small molecule cell cycle inhibitor to control cell growth and improve specific productivity and product quality of recombinant proteins in CHO cell cultures. Biotechnol Bioeng 2014; 112(1):141–55.
- Reference17. Eon-Duval A, Broly H, Gleixner R. Quality attributes of recombinant therapeutic proteins: An assessment of impact on safety and efficacy as part of a quality by design development approach. Biotechnol Prog 2012; 28(3):608–22.
- Reference18. Zhang X, Sun YT, Tang H, Fan L, Hu D, Liu J, et al. Culture temperature modulates monoclonal antibody charge variation distribution in Chinese hamster ovary cell cultures. Biotechnol Lett 2015; 37(11):2151–7.
- Reference19. Zhang X, Tang H, Sun YT, Liu X, Tan WS, Fan L. Elucidating the effects of arginine and lysine on a monoclonal antibody C-terminal lysine variation in CHO cell cultures. Appl Microbiol Biotechnol 2015; 99(16):6643–52.
- Reference20. Luo J, Zhang J, Ren D, Tsai WL, Li F, Amanullah A, et al. Probing of C-terminal lysine variation in a recombinant monoclonal antibody production using Chinese hamster ovary cells with chemically defined media. Biotechnol Bioeng 2012; 109(9):2306–15.
- Reference21. Kaschak T, Boyd D, Lu F, Derfus G, Kluck B, Nogal B, et al. Characterization of the basic charge variants of a human IgG1: Effect of copper concentration in cell culture media. MAbs 2011; 3(6).
There are 21 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Microbiology |
| Journal Section | Research Article |
| Authors | |
| Publication Date | January 1, 2022 |
| Submission Date | May 7, 2021 |
| Published in Issue | Year 2022 |