Towards energy-based dynamic optimization of monoclonal antibody producing GS-NS0 Cultures

Mammalian cell culture systems produce clinically important high-value biologics, such as monoclonal antibodies (mAb). Cell lines transfected with the Glutamine Synthetase (GS) gene are amongst the most industrially significant mAb production systems due to the high yields they achieve. Metabolic models of GS culture systems presented thus far take into account only glucose as a growth limiting nutrient, neglecting the fact that in the absence of glutamine in the media, glutamate becomes a necessary dietary component in GS systems. Previously, we have presented the development of a systematic framework for modelling of mammalian cell bioprocesses. Herein, we present, for the first time, the development of a dynamic model describing growth and monoclonal antibody formation in GS-NS0 cell cultures that interlinks cellular growth rate with the availability of both glucose and glutamate. This is the first step, of many, towards the derivation of a dynamic model that interlinks the availability of ATP, through the dietary intake of the cell, to its growth and productivity characteristics. Such a model would facilitate the derivation of an optimal feeding profile, constraining the amount of provided energy through the feed to the required minimal, hence avoiding the excessive feeding of glucose which in turn shifts metabolism towards energy inefficient pathways.