Evaluation of Chinese hamster ovary cell stability during repeated batch culture for large-scale antibody production

• Published in: Journal of bioscience and bioengineering Vol. 109; no. 3; pp. 274 - 280
• Main Authors: Kaneko, Yoshihiro, Sato, Ryuji, Aoyagi, Hideki
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.03.2010; Elsevier
• Subjects: Animals; Antibodies, Monoclonal - biosynthesis; ANTICORPS MONOCLONAL; ANTICUERPOS MONOCLONALES; Biological and medical sciences; BIOREACTEUR; BIOREACTORS; BIORREACTORES; Biotechnology; CELL CULTURE; Cell Culture Techniques - methods; Cell Survival; CHO Cells; CLONAL VARIATION; Cricetinae; Cricetulus; CULTIVO DE CELULAS; CULTURE DE CELLULE; Fundamental and applied biological sciences. Psychology; GENE TRANSFER; Genetic Enhancement - methods; HAMSTER; HAMSTERS; HM1.24 antigen; http://www.fao.org/aos/agrovoc#c_24051; http://www.fao.org/aos/agrovoc#c_24846; http://www.fao.org/aos/agrovoc#c_27469; http://www.fao.org/aos/agrovoc#c_27611; http://www.fao.org/aos/agrovoc#c_3482; http://www.fao.org/aos/agrovoc#c_5456; http://www.fao.org/aos/agrovoc#c_7178; MONOCLONAL ANTIBODIES; Monoclonal antibody; OVAIRE; OVARIES; OVARIOS; Protein Engineering - methods; Recombinant CHO cell; Scaled-down cell culture; TRANSFERENCIA DE GENES; TRANSFERT DE GENE; VARIACION CLONAL; VARIATION CLONALE; Scaled-down cell culture; Recombinant CHO cell; Monoclonal antibody; HM1.24 antigen; Antigen; Cell culture; Stability; Batchwise; Production; Recombinant cell; CHO cell line
• ISSN: 1389-1723; 1347-4421
• DOI: 10.1016/j.jbiosc.2009.09.044

Pharmaceutical manufacturing plants can be operated continuously for several months. It is therefore important to use cells with long-term stability for the production of active ingredients. We investigated the reliability and long-term stability of an antibody-producing cell line. A recombinant Chinese hamster ovary (CHO) cell line was cultivated in spinner flasks and reactors, including a practical production-scale reactor (1600 L), for 109 days to produce monoclonal antibodies against the HM1.24 antigen. During cultivation, the cells remained stable and there was an increase in the rate of cell proliferation, yielding viable cells at high density. A decrease in cell-specific productivity was associated with this increase in the rate of cell proliferation. The cells were genetically stable and other measures of cellular function remained consistent throughout the cultivation period.