Open AccessStress‐induced increase of monoclonal antibody production in CHO cells
Author(s) -
Schellenberg Jana,
Nagraik Tamanna,
Wohlenberg Ole Jacob,
Ruhl Sebastian,
Bahnemann Janina,
Scheper Thomas,
Solle Dörte
Publication year - 2022
Publication title -
engineering in life sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.547
H-Index - 57
eISSN - 1618-2863
pISSN - 1618-0240
DOI - 10.1002/elsc.202100062
Subject(s) - chinese hamster ovary cell , monoclonal antibody , bioreactor , titer , cell , biopharmaceutical , recombinant dna , cell growth , cell culture , chemistry , biology , microbiology and biotechnology , antibody , biochemistry , immunology , genetics , organic chemistry , gene
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. CO 2 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.