The impact of process temperature on mammalian cell lines and the implications for the production of recombinant proteins in CHO cells

The use of a temperature-shift to subphysiological temperatures (<37 degrees C) during the culturing of mammalian cell lines engineered to produce a recombinant protein is widely utilized. The effect of such a temperature shift on both the cellular responses and recombinant protein yield is not uniform and is both cell- and product-specific. Despite this, the understanding of the cellular responses to mild subphysiological temperature (27-35 degrees C) culturing has developed markedly over the last decade and, as such, opportunities exist to harness this knowledge to further improve product yields and quality at subphysiological temperatures. In this review we describe the mammalian cell response to mild subphysiological temperature, the effects on recombinant protein production under such conditions, those mechanisms that appear to underpin increases in productivity at such temperatures, and potential future innovations and directions that may further enhance the use of such conditions during bioprocessing of recombinant protein products.