Maximizing interferon-gamma production by Chinese hamster ovary cells through temperature shift optimization:...

Area of Science:

• Biotechnology
• Cell Culture Engineering
• Bioprocess Optimization

Background:

• Chinese hamster ovary (CHO) cell lines are crucial for biopharmaceutical production.
• Lowering culture temperature (e.g., to 32°C) significantly increases specific productivity of interferon-gamma (IFN-gamma) but slows cell growth.
• This temperature-dependent growth arrest limits overall volumetric productivity in standard batch cultures.

Purpose of the Study:

• To investigate a biphasic temperature control strategy to enhance IFN-gamma volumetric productivity.
• To develop and validate a predictive model for optimizing the temperature shift point.

Main Methods:

• Utilized a biphasic culture process: initial growth at 37°C followed by a shift to 32°C.
• Developed and validated a mathematical model to determine the optimal timing for the temperature shift.
• Compared volumetric productivity under different temperature conditions (37°C, 32°C, and biphasic).

Main Results:

• A 2-fold increase in specific productivity was observed at 32°C compared to 37°C.
• The biphasic approach, with a temperature shift after 3 days, increased IFN-gamma volumetric productivity by 40% compared to constant 32°C culture.
• This strategy achieved a 90% increase in volumetric productivity compared to constant 37°C culture, without reducing total product concentration.

Conclusions:

• A biphasic temperature control strategy effectively overcomes the limitations of slow growth at low temperatures.
• The developed modeling framework provides a reliable method for optimizing temperature shifts in bioprocesses.
• This approach significantly enhances volumetric productivity for IFN-gamma production in CHO cells.