Production of monoclonal antibody using free‐suspended and immobilized hybridoma cells: Effect of serum

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Abstract
The effect of serum on cell growth and monoclonal antibody (MAb) productivity was studied in a repeated fedbatch mode using both free-suspended and immobilized S3H5/γ2bA2 hybridoma cells. In the suspension culture, serum influenced the cell growth rate but not the specific MAb productivity. The average specific growth rate of the suspension culture in medium containing 10% serum was approximately 0.99 ± 0.12 day−1 (±standard deviation), while that in medium containing 1% serum was approximately 0.73 ± 0.12 day−1. The specific MAb productivity was almost constant at 3.69 ± 0.57 μg/106 cells/day irrespective of serum concentration reached a maximum at ca. 1.8 × 106 cells/mL of medium in 10% serum medium, and the cell concentration was gradually reduced to 1%. The specific MAb productivity of the immobilized cells was more than three times higher than that of the free-suspended cells. The amount of serum in the medium did not influence the specific MAb production rate of the immobilized cells. The maintenance of high cell concentration and the enhanced specific MAb productivity of the immobilized cell culture resulted in a higher volumetric MAb productivity. In addition, MAb yield in the immobilized cell culture with medium containing 1% serum was 2.2 mg/mL of serum, which was approximately three times higher than that in the suspension culture.