Enhancing effect of low culture temperature on specific antibody productivity of recombinant Chinese hamster ovary cells: Clonal variation

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To understand the different responses of recombinant Chinese hamster ovary (rCHO) cells to low culture temperature regarding specific productivity (q), 12 parental clones and their corresponding amplified clones producing a humanized antibody were cultivated at 32 and 37 degreesC. The specific growth rate of all clones, including both parental and amplified clones, decreased by 30-63% at 32 degreesC, compared to rates at 37degreesC. In contrast, their specific antibody productivity (q(Ab)) was significantly enhanced at 32 degreesC. Furthermore, the degree of q(Ab) enhancement at 32 degreesC varied a lot from 4- to 25-fold among the parental clones. At 32 degreesC, most of the amplified clones, regardless of methotrexate (MTX) levels, also showed enhanced q(Ab) but to a lesser extent than their parental clones. However, clone 14 amplified at 0.32 muM MTX (clone 14-0.32) and clone 20 amplified at 1 muM MTX (clone 20-1.00), unlike their parental clones, did not show enhanced q(Ab) at 32 degreesC. Thus, it was found that the enhancing effect of low culture temperature on q of rCHO cells depends on clones. Taken together, the results obtained here emphasize the importance of clonal selection for the successful application of low culture temperature to the enhanced foreign protein production in rCHO cells.
Publisher
AMER CHEMICAL SOC
Issue Date
2004
Language
English
Article Type
Article
Keywords

ALPHA-AMIDATING ENZYME; GENE-COPY-NUMBER; CHO-CELLS; TRANSCRIPTION LEVEL; EXPRESSION; BUTYRATE; ERYTHROPOIETIN; AMPLIFICATION; QUALITY

Citation

BIOTECHNOLOGY PROGRESS, v.20, no.6, pp.1683 - 1688

ISSN
8756-7938
DOI
10.1021/bp049847f
URI
http://hdl.handle.net/10203/85339
Appears in Collection
BS-Journal Papers(저널논문)
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