Improvement of a mammalian cell culture process by adaptive, model-based dialysis fed-batch cultivation and suppression of apoptosis.
Both conventional and genetic engineering techniques can significantly improve the performance of animal cell cultures for the large-scale production of pharmaceutical products. In this paper, the effect of such techniques on cell yield and antibody production of two NS0 cell lines is presented. On the one hand, the effect of fed-batch cultivation using dialysis is compared to cultivation without dialysis. Maximum cell density could be increased by a factor of approximately 5-7 by dialysis fed-batch cultivation. On the other hand, suppression of apoptosis in the NS0 cell line 6A1 bcl-2 resulted in a prolonged growth phase and a higher viability and maximum cell density in fed-batch cultivation in contrast to the control cell line 6A1 (100)3. These factors resulted in more product formation (by a factor of approximately 2). Finally, the adaptive model-based OLFO controller, developed as a general tool for cell culture fed-batch processes, was able to control the fed-batch and dialysis fed-batch cultivations of both cell lines.
D000222:Adaptation, Physiological; D000465:Algorithms; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D017209:Apoptosis; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D003198:Computer Simulation; D003956:Dialysis / Q000379:methods*; D005246:Feedback; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008954:Models, Biological; D009101:Multiple Myeloma / Q000473:pathology / Q000503:physiopathology*; D015202:Protein Engineering / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D011786:Quality Control; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins