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 si ngle cell suspension. The BHK lines were grown either as suspended nat ural aggregates or on Cytodex 3 microcarriers. The data for F3b10 show ed that the cell-specific rAb production rate (Qs(rAb)) increased in p arallel with increases in the specific growth rate (mu). A similar res ult was obtained for suspended aggregate cultures of both recombinant BHK cell lines. In contrast, for microcarrier cultures of both BHK cel l lines, Qs(product) increased as mu decreased. This report shows that the relationship between cell growth and Qs(product) for the cell lin es and products studied is dependent upon the culture process. In syst ems where recombinant cells are growing as a single cell suspension or within a natural suspension aggregrate, Qs(product) increased with in creases in mu. In such systems, the cells have a rounded morphology. W hen cells were grown on microcarriers, Qs(product) decreased as mu inc reased. Cells growing attached to a surface are flat and elongated. Th e observed differences in the relationship of Qs(product) to mu are co rrelated with changes in cell morphology. The relationship between Qs( product) and mu is also affected by the choice of cell line.