Animal Cells, Hybridomas, Human Antibody Production

Abstract

Cellular response to perturbations in the microenvironment manifests as a surge of physiological changes that have great impact on cellular metabolism and propagation. In bioprocess systems, mammalian cells engineered for the production of monoclonal antibodies or therapeutic proteins are sensitive to fluctuations in the culture environment. These fluctuations often directly translate to changes in maximum attainable cell concentration and/or specific protein productivity. In conjunction with feeding strategy optimization, the ability to understand and optimize the physical environment of animal culture systems is key to achieving a process that delivers consistent production of high titer batches. In this article we have reviewed comprehensively two critical physical culture parameters: osmolality and temperature, for their effects on general cellular physiology as well as their impacts on overall culture performance in bioprocess systems. Extreme levels of osmolality lead to volume‐regulatory responses, cytoskeletal reorganization, and trigger distinct cellular signaling pathways. Cellular responses to hypothermic conditions include reduced metabolic and growth rates, reduction of apoptosis frequency, and a cold‐shock response which involves the increased synthesis of several proteins. Exposure of cells to hyperosmotic conditions and/or subphysiological temperature (32–35°C) has been shown to enhance specific protein productivity in bioprocess systems. As live viruses are also commonly produced in industrial cell culture systems for vaccine processes, we have extended the scope of this article to include the effects of fluctuations in culture osmolality and temperature on the production of live viruses.