Chemicals Affecting Autophagy in rCHO Cell Cultures and Their Impacts on Therapeutic Protein Production Processes.

Abstract

Autophagy is a cellular process that is essential for maintaining homeostasis in mammalian cells by degrading and recycling intracellular components, particularly under stress conditions. To achieve high therapeutic protein production in recombinant Chinese hamster ovary (rCHO) cells, it is necessary to develop a fed-batch culture process using optimized culture media that maintains a rapid growth rate and extends the culture longevity of cell lines with high specific protein productivity. During the development of these culture processes, stressful conditions, such as rapid nutrient deprivation and hyperosmolarity, which may occur through the repeated addition of nutrient concentrates, can induce autophagy in rCHO cells. Proper modulation of autophagy promotes cell survival by alleviating cellular stress rather than promoting cell death, thereby improving cell viability and therapeutic protein production in rCHO cell-based processes. This review discusses the various chemicals known to inhibit or induce autophagy in rCHO cell cultures, their mechanisms of action, and their effects on the production efficiency of therapeutic proteins. Understanding these mechanisms provides insight into improving the productivity and quality of therapeutic proteins during rCHO cell-based bioprocesses.