Sandadi Sandeepa, Ensari Semsi, Kearns Brian
Biotechnology Development, Schering-Plough Research Institute, 1011 Morris Avenue, Union, New Jersey 07083, USA.
Biotechnol Prog. 2005 Sep-Oct;21(5):1537-42. doi: 10.1021/bp0501266.
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.
单克隆抗体的大规模生产需要开发一种具有商业可行性的工艺，该工艺要使用合适的生物反应器、培养基和最佳补料策略。在开发提高抗体滴度的补料策略时，评估限制性底物对细胞培养寿命和抗体生产的影响至关重要。在本研究中，葡萄糖和L-谷氨酰胺被确定为限制性底物，并在小规模实验中评估了它们对培养寿命和抗体生产的影响。结果表明，最佳补料策略应考虑培养物的渗透压分布。用于优化抗体生产的启发式方法表明，分批补料培养优于分批培养，并且在生长阶段保持低渗透压会增加累积活细胞密度，从而导致最终抗体滴度更高。
