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Kinetic study on HBs-MAb production in continuous cultivation
M Harigae1, M Matsumura, H Kataoka
1Institute of Applied Biochemistry, University of Tsukuba Tennodai, Ibaraki, Japan.
Journal of Biotechnology
|May 31, 1994
Summary
Continuous culture of hybridoma cells in a membrane reactor achieved high cell densities for monoclonal antibody (MAb) production. This method optimizes MAb yield by maintaining elevated viable cell concentrations, crucial for hepatitis B surface antigen therapies.
Area of Science:
- Biotechnology
- Cell Culture Engineering
- Immunology
Background:
- Monoclonal antibodies (MAbs) are vital therapeutics, requiring efficient production methods.
- High cell density cultures are challenging to maintain in conventional systems.
- Hepatitis B surface antigen (HBsAg) specific MAbs are important for diagnostics and therapeutics.
Purpose of the Study:
- To investigate continuous cultivation of hybridoma cells in a membrane reactor.
- To achieve and maintain high viable cell concentrations for MAb production.
- To characterize MAb production, glucose, and glutamine metabolism at high cell density.
Main Methods:
- Continuous culture of T0405 mouse-mouse hybridoma cells in a membrane reactor.
- Partial cell bleeding strategy to control viable cell concentration.
- Steady-state analysis of MAb production and cellular metabolism.
Main Results:
- Viable cell concentrations were maintained between 1.0 x 10(6) and 4.0 x 10(6) cells/ml.
- Monoclonal antibody (MAb) production was growth-associated.
- Ammonia production correlated with glutamine for cell maintenance, while lactate production was higher during cell growth on glucose.
Conclusions:
- Membrane reactor with partial cell bleeding enables high cell density continuous culture.
- Optimized cell density enhances MAb production efficiency.
- Understanding metabolic pathways is key to optimizing high-density cell culture for biopharmaceutical production.