Effects of Metal Ions on Antibody Production and Charge Heterogeneity in CHO Cell Cultures

doi:10.13560/j.cnki.biotech.bull.1985.2016.08.034

Abstract

Abstract: The objective of this work is to get insights into the role of metal ions in the production of the monoclonal antibody（mAb）during Chinese hamster ovary（CHO）cell cultures. Cell growth,antibody production and antibody charge distribution at different concentrations of copper and zinc ions during cell cultures were comprehensively investigated. It was found that 120 nmol/L copper ion and 50 µmol/L zinc ion were the optimal concentrations for cell growth and antibody production. Excessively low or high levels of copper and zinc ions brought negative impacts on cell growth and viability maintenance. Additionally,copper ion and zinc ion,as the inhibitor and cofactor of basic carboxypeptidase respectively,showed considerable effects on antibody charge distribution. The medium containing 50 nmol/L copper ion and 50 μmol/L zinc ion was the most conducive to the reduction of charge variants and the increase of main species. Both excessively low or high concentrations of copper and zinc ions led to the increase of the antibody charge variants and the reduction of main species. The concentrations and ratios of copper and zinc ions altered the enzymatic digestion at antibody C-terminal lysine,subsequently affected the content of the basic variant. Additionally,the working space of copper and zinc ions for process control of antibody charge variants was preliminarily discussed. In conclusion,the metal ions play important roles in cell growth,mAb production and mAb charge distribution during CHO cell cultures.

Key words: animal cell culture, charge distribution, metal ions, monoclonal antibody

ZHANG Xin-tao ,TANG Hong-ping ,ZHAO Liang ,FAN Li, LIU Xu-ping, MIAO Shi-wei, TAN Wen-song. Effects of Metal Ions on Antibody Production and Charge Heterogeneity in CHO Cell Cultures[J]. Biotechnology Bulletin, 2016, 32(8): 233-241.

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