title: A high-yielding, generic fed-batch process for recombinant antibody production of GS-engineered cell lines.
abstract: An animal-component-free and chemically defined fed-batch process for GS-engineered cell lines producing recombinant antibodies has been developed. The fed-batch process relied on supplying sufficient nutrients to match their consumption, simultaneously minimizing the accumulation of by-products (lactate and osmolality). The proportionalities of nutritional consumption were determined by direct analysis. The robust, metabolically responsive feeding strategy was based on the offline measurement of glucose. The fed-batch process was shown to perform equivalently in GS-CHO and GS-NS0 cultures. Compared with batch cultures, the fed-batch technology generated the greater increase in cell yields (5-fold) and final antibody concentrations (4-8 fold). The majority of the increase in final antibody concentration was a function of the increased cell density and the prolonged culture time. This generic and high-yielding fed-batch process would shorten development time, and ensure process stability, thereby facilitating the manufacture of therapeutic antibodies by GS-engineered cell lines.
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Yating
authors.initials: Y
authors.lastname: Sun
authors.forename: Tianci
authors.initials: T
authors.lastname: Kou
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Wen-Song
authors.initials: WS
authors.lastname: Tan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D002452:Cell Count; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D006224:Cricetinae; D003470:Culture Media / Q000737:chemistry; D005947:Glucose / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis; D051379:Mice; D009994:Osmolar Concentration; D011994:Recombinant Proteins / Q000096:biosynthesis*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D003470:Culture Media; D011994:Recombinant Proteins; D019344:Lactic Acid; D005974:Glutamate-Ammonia Ligase; D005947:Glucose