Heuristic optimization of antibody production by Chinese hamster ovary cells.
Large-scale production of monoclonal antibodies necessitates the development of a commercially viable process using the appropriate bioreactors, culture medium, and optimal feeding strategies. In the development of feeding strategies for higher antibody titers it is critical to assess the effects of limiting substrates on cell culture longevity and antibody production. In this study, glucose and L-glutamine were identified as limiting substrates and their effects on culture longevity and antibody production were evaluated in small-scale experiments. The results suggested that an optimal feeding strategy should account for the osmolality profile of the culture. The heuristic approach taken to optimize the antibody production showed that the fed-batch cultivation is superior to batch culture and maintaining low osmolality during growth phase increases cumulative viable cell density and thus leads to higher final antibody titer.
Sandadi
Sandeepa
S
Biotechnology Development, Schering-Plough Research Institute, 1011 Morris Avenue, Union, New Jersey 07083, USA.
Ensari
Semsi
S
Kearns
Brian
B
D000465:Algorithms; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D016466:CHO Cells / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods*; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D008954:Models, Biological; D015202:Protein Engineering / Q000379:methods*; D011786:Quality Control
D000911:Antibodies, Monoclonal; D005973:Glutamine; D005947:Glucose