The mammalian cells are the most preferred expression platform due to their ability to perform post-translational modifications for the production of complex therapeutic proteins also referred as biologics or biotherapeutics. The success of antibody therapeutics has led to an increased focus on developing processes to increase yield and improve product quality. The production of high quantities of recombinant Abs imposes considerable strain on the metabolic and redox homeostasis of the cells due to large energy demands associated with the synthesis, folding, quality control, and secretion of expressed antibody. The consequence of high energy demand is increased oxidative stress, which can result in elevated levels of reactive oxygen species (ROS) causes irreversible oxidative damage to cellular machinery leading to cell death. The cell culture processes are known to have a significant effect on expression as well as quality of expressed protein. However, intracellular response of cells to redox stress as well as molecular mechanism of cytoprotective behaviour of anti-oxidants has not been fully explored. This study delineates the mechanistic role of oxidants and ROS scavengers in regulating quantity of expressed protein at shake flask level. The study explores the role of redox stress in modulating the critical quality attributes (CQAs) of expressed protein. The effect of oxidative stress upon charge variants and aggregation has been determined. Chinese hamster ovary (CHO) cell line expressing IgG<sub>1</sub> has been subjected to the deliberate imposition of increased oxidative stress during culture and their effect on cell growth and protein production have been investigated. The intracellular mechanisms by which ROS scavengers affect the productivity of these cells via inhibiting apoptosis and increase in cell pool with high membrane potential has been established.  The protein product quantity as well as quality in response to oxidative stress have been examined which will subsidise the role of cell culture performance affecting process understanding and modulating targeted recombinant protein product quantity and quality.<br/>

Role of redox stress in modulating CQAs of recombinant antibody expressed in mammalian cell culture processes

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.