Journal of Microbiology and Biotechnology
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2013 ; 23(9): 1327~1338

AuthorSeong-Won Song, Song-Jae Lee, Chang-Young Kim, Jae-Kyung Song, Eui-Jung Jung, Yong Bock Choi, Sung-Won Min, Jong-Won Oh
AffiliationGraduate Program in Biomaterials Science and Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea,Bioresearch Institute, Yooyoung Pharmaceuticals Co. Ltd., Guro-dong, Gur-gu, Seoul, 152-719, Republic of Korea
TitleInhibition of Tumor Growth in a Mouse Xenograft Model by the Humanized Anti-HGF Monoclonal Antibody YYB-101 Produced in a Large-Scale CHO Cell Culture
PublicationInfo J. Microbiol. Biotechnol.2013 ; 23(9): 1327~1338
AbstractThe humanized anti-hepatocyte growth factor (HGF) monoclonal antibody (mAb) YYB-101 is a promising therapeutic candidate for treating various cancers. In this study, we developed a bioprocess for large-scale production of YYB-101 and evaluated its therapeutic potential for tumor treatment using a xenograft mouse model. By screening diverse chemically defined basal media formulations and by assessing the effects of various feed supplements and feeding schedules on cell growth and antibody production, we established an optimal medium and feeding method to produce 757 mg/l of YYB-101 in flask cultures, representing a 7.5-fold increase in titer compared with that obtained under non-optimized conditions. The optimal dissolved oxygen concentration for antibody production was 70% pO2. A pH shift from 7.2 to 7.0, rather than controlled pH of either 7.0 or 7.2, resulted in productivity improvement in 5 L and 200 L bioreactors, yielding 737 and 830 mg/ml of YYB-101, respectively. The YYB-101 mAb highly purified by affinity chromatography using a Protein A column and two-step ion exchange chromatography effectively neutralized HGF in a cell-based assay and showed potent tumor suppression activity in a mouse xenograft model established with human glioblastoma cells.
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KeywordsChinese hamster ovary cells, anti-human hepatocyte growth factor monoclonal ant, humanized antibody, process development, anti-HGF antibody YYB-101, anti-tumor activity
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