Details
| Original language | English |
|---|---|
| Pages (from-to) | 427-436 |
| Number of pages | 10 |
| Journal | Engineering in life sciences |
| Volume | 22 |
| Issue number | 5 |
| Early online date | 7 May 2022 |
| Publication status | Published - May 2022 |
Abstract
Monoclonal antibodies (mAbs) are of great interest to the biopharmaceutical industry due to their widely used application as human therapeutic and diagnostic agents. As such, mAb require to exhibit human-like glycolization patterns. Therefore, recombinant Chinese hamster ovary (CHO) cells are the favored production organisms; many relevant biopharmaceuticals are already produced by this cell type. To optimize the mAb yield in CHO DG44 cells a corelation between stress-induced cell size expansion and increased specific productivity was investigated. CO2 and macronutrient supply of the cells during a 12-day fed-batch cultivation process were tested as stress factors. Shake flasks (500 mL) and a small-scale bioreactor system (15 mL) were used for the cultivation experiments and compared in terms of their effect on cell diameter, integral viable cell concentration (IVCC), and cell-specific productivity. The achieved stress-induced increase in cell-specific productivity of up to 94.94.9%–134.4% correlates to a cell diameter shift of up to 7.34 μm. The highest final product titer of 4 g/L was reached by glucose oversupply during the batch phase of the process.
Keywords
- cell size, cell-specific productivity, CHO, mAb, stress
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biotechnology
- Environmental Science(all)
- Environmental Engineering
- Chemical Engineering(all)
- Bioengineering
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In: Engineering in life sciences, Vol. 22, No. 5, 05.2022, p. 427-436.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Stress-induced increase of monoclonal antibody production in CHO cells
AU - Schellenberg, Jana
AU - Nagraik, Tamanna
AU - Wohlenberg, Ole Jacob
AU - Ruhl, Sebastian
AU - Bahnemann, Janina
AU - Scheper, Thomas
AU - Solle, Dörte
N1 - Funding Information: The authors would like to thank Sartorius Stedim Cellca GmbH, DE for providing the antibody producing DG44 CHO cell line and acknowledge the corporation. Furthermore, a sincere thank you goes to Christopher Heuer and Katharina V. Meyer for their proofreading and support of this article. Open Access funding enabled and organized by Projekt DEAL.
PY - 2022/5
Y1 - 2022/5
N2 - Monoclonal antibodies (mAbs) are of great interest to the biopharmaceutical industry due to their widely used application as human therapeutic and diagnostic agents. As such, mAb require to exhibit human-like glycolization patterns. Therefore, recombinant Chinese hamster ovary (CHO) cells are the favored production organisms; many relevant biopharmaceuticals are already produced by this cell type. To optimize the mAb yield in CHO DG44 cells a corelation between stress-induced cell size expansion and increased specific productivity was investigated. CO2 and macronutrient supply of the cells during a 12-day fed-batch cultivation process were tested as stress factors. Shake flasks (500 mL) and a small-scale bioreactor system (15 mL) were used for the cultivation experiments and compared in terms of their effect on cell diameter, integral viable cell concentration (IVCC), and cell-specific productivity. The achieved stress-induced increase in cell-specific productivity of up to 94.94.9%–134.4% correlates to a cell diameter shift of up to 7.34 μm. The highest final product titer of 4 g/L was reached by glucose oversupply during the batch phase of the process.
AB - Monoclonal antibodies (mAbs) are of great interest to the biopharmaceutical industry due to their widely used application as human therapeutic and diagnostic agents. As such, mAb require to exhibit human-like glycolization patterns. Therefore, recombinant Chinese hamster ovary (CHO) cells are the favored production organisms; many relevant biopharmaceuticals are already produced by this cell type. To optimize the mAb yield in CHO DG44 cells a corelation between stress-induced cell size expansion and increased specific productivity was investigated. CO2 and macronutrient supply of the cells during a 12-day fed-batch cultivation process were tested as stress factors. Shake flasks (500 mL) and a small-scale bioreactor system (15 mL) were used for the cultivation experiments and compared in terms of their effect on cell diameter, integral viable cell concentration (IVCC), and cell-specific productivity. The achieved stress-induced increase in cell-specific productivity of up to 94.94.9%–134.4% correlates to a cell diameter shift of up to 7.34 μm. The highest final product titer of 4 g/L was reached by glucose oversupply during the batch phase of the process.
KW - cell size
KW - cell-specific productivity
KW - CHO
KW - mAb
KW - stress
UR - http://www.scopus.com/inward/record.url?scp=85125053768&partnerID=8YFLogxK
U2 - 10.1002/elsc.202100062
DO - 10.1002/elsc.202100062
M3 - Article
AN - SCOPUS:85125053768
VL - 22
SP - 427
EP - 436
JO - Engineering in life sciences
JF - Engineering in life sciences
SN - 1618-0240
IS - 5
ER -