title: Inhibition 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.
abstract: The 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.
authors.affiliation: Graduate Program in Biomaterials Science and Engineering, Yonsei University, Seoul 120-749, Republic of Korea, Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea, Translational Research Center for Protein Function Control, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Seong-Won
authors.initials: SW
authors.lastname: Song
authors.forename: Song-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Chang-Young
authors.initials: CY
authors.lastname: Kim
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Song
authors.forename: Eui-Jung
authors.initials: EJ
authors.lastname: Jung
authors.forename: Yong Bock
authors.initials: YB
authors.lastname: Choi
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Min
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Oh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000302:isolation & purification / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000235:genetics / Q000302:isolation & purification / Q000627:therapeutic use*; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D049109:Cell Proliferation / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D017228:Hepatocyte Growth Factor / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017228:Hepatocyte Growth Factor