A STRUCTURED MODEL FOR MONOCLONAL-ANTIBODY SYNTHESIS IN EXPONENTIALLY GROWING AND STATIONARY PHASE HYBRIDOMA CELLS

被引:73
作者
BIBILA, T
FLICKINGER, MC
机构
[1] UNIV MINNESOTA,DEPT BIOCHEM,ST PAUL,MN 55108
[2] UNIV MINNESOTA,DEPT CHEM ENGN & MAT SCI,ST PAUL,MN 55108
[3] UNIV MINNESOTA,INST ADV STUDIES BIOL PROC TECHNOL,ST PAUL,MN 55108
关键词
D O I
10.1002/bit.260370304
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
An initial structured unsegregated kinetic model describing monoclonal antibody synthesis by a murine hybridoma cell line (9.2.27) grown in 1 liter batch cultures is described. The model is based on the intracellular balances of the heavy and light chain coding mRNAs, the intracellular balances of heavy and light chains and the description of the kinetics of heavy and light chain assembly. Model parameters were varied with specific growth rate in order to account for changes in the rates of antibody synthesis and secretion with entrance of the cells from the exponential into the stationary phase of growth. The parameters were varied based on experimental data obtained in our laboratory on the variation of total cellular RNA content and the half-lives of heavy (H) and light (L) chain mRNAs with specific growth rate, and data from other investigators on immunoglobulin synthesis and secretion. The model successfully predicts the experimentally observed decrease in the intracellular heavy and light chain mRNA levels with entrance of 9.2.27 cells from the exponential into the stationary phase of growth, as well as the extracellular accumulation of antibody (IgG2a) during batch culture.
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页码:210 / 226
页数:17
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