A high-yielding, generic fed-batch process for recombinant antibody production of GS-engineered cell lines.
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.
Fan
Li
L
The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Zhao
Liang
L
Sun
Yating
Y
Kou
Tianci
T
Zhou
Yan
Y
Tan
Wen-Song
WS
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
D000911:Antibodies, Monoclonal; D003470:Culture Media; D011994:Recombinant Proteins; D019344:Lactic Acid; D005974:Glutamate-Ammonia Ligase; D005947:Glucose