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Type: Journal article
Title: Modulation of Cell Cycle for Enhancement of Antibody Productivity in Perfusion Culture of NS0 Cells
Author: Ibarra, N.
Bi, J.
Shuttleworth, J.
Al-Rubeai, M.
Watanabe, S.
Citation: Biotechnology Progress, 2003; 19(1):224-228
Publisher: Amer Chemical Soc
Issue Date: 2003
ISSN: 8756-7938
Abstract: A prolonged period of high productivity at high cell density is desirable for industrial production of biopharmaceuticals. Previous efforts have shown that cessation of cell proliferation in low cell density culture results in increased productivity. We report here further results on multigenic manipulation of cell cycle and apoptosis to enhance productivity at high cell density. The NS0 6A1/4-9F myeloma cell line, which constitutively expresses a chimeric IgG4 antibody and inducibly expresses the p21CIP1 cyclin-dependent kinase inhibitor has been further engineered to constitutively overexpress the Y28 mutant Bcl-2 anti-apoptotic protein. The effects of overexpression of p21CIP1 and Bcl-2 on cell proliferation, cell viability, and antibody production has been investigated in batch and continuous perfusion cultures. In both cultures the p21CIP1 protein arrested cell proliferation, confirming the previous results in low-density culture of 4-fold increase in antibody production, whereas mutant Bcl-2 expression has not resulted in any significant improvement in cell viability of arrested cells. This study demonstrates that it is possible to enhance the productivity of relatively high-density continuous mammalian cell cultures by arresting the cell cycle in G1 phase.
Keywords: Tumor Cells, Cultured; Animals; Mice; Multiple Myeloma; Cyclins; Immunoglobulin G; Proto-Oncogene Proteins c-bcl-2; Antibodies; Cell Count; Cloning, Molecular; Protein Engineering; Cell Cycle; Cell Survival; Gene Expression Regulation; Quality Control; Cyclin-Dependent Kinase Inhibitor p21
Description: © 2002 American Chemical Society and American Institute of Chemical Engineers
RMID: 0020081602
DOI: 10.1021/bp025589f
Appears in Collections:Chemical Engineering publications

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