Expression of recombinant antibody and secreted alkaline phosphatase in mammalian cells. Influence of cell line and culture system upon production kinetics

The growth and productivity of an Sp2/0 cell line, F3b10, expressing a recombinant antibody (rAb) and BHK21 cells expressing either the same rAb from the same plasmids (BHK.IgG) or secreted alkaline phosphatase (SEAP) (BHK.SEAP) were investigated. The F3b10 line was grown as a single cell suspension. The BHK lines were grown either as suspended natural aggregates or on Cytodex 3 microcarriers. The data for F3b10 showed that the cell-specific rAb production rate (Qs _rAb) increased in parallel with increases in the specific growth rate (). A similar result was obtained for suspended aggregate cultures of both recombinant BHK cell lines. In contrast, for microcarrier cultures of both BHK cell lines, Qs _product increased as decreased. This report shows that the relationship between cell growth and Qs _product for the cell lines and products studied is dependent upon the culture process. In systems where recombinant cells are growing as a single cell suspension or within a natural suspension aggregate, Qs _product increased with increases in . In such systems, the cells have a rounded morphology. When cells were grown on microcarriers, Qs _product decreased as increased. Cells growing attached to a surface are flat and elongated. The observed differences in the relationship of Qs _product to are correlated with changes in cell morphology. The relationship between Qs _product and is also affected by the choice of cell line. Correspondence to: A. J. Racher