Biphasic Culture Strategy Based on Hyperosmotic Pressure for Improved Humanized Antibody Production in Chinese Hamster Ovary Cell Culture

Abstract

Hyperosmotic pressure has been recognized as being an economical solution to increase q in hybridoma (1,4), transfectoma (2), and rCHO cell cultures (5). Despite the potential of commercial strategies based on hyperosmotic pressure, the use of hyperosmolar medium has not been popular because cell growth is depressed at elevated osmolality. (1,4). Among various strategies to overcome depressed cell growth at elevated osmolality, the use of osmoprotective compounds such as glycine betaine is probably most feasible for improved foreign protein production (3,5). However, the efficacy of the simultaneous use of hyperosmotic pressure and glycine betaine was found to be variable among rCHO cell lines (5). In this study, we investigated the feasibility of simple biphasic culture strategy based on hyperosmotic culture for improved foreign protein production from rCHO cells. In the biphasic culture, the rCHO cells producing humanized antibody are first cultivated in the standard medium for cell growth and then in the hyperosmolar medium for antibody production.