LONG-TERM STABLE PRODUCTION OF MONOCYTE-COLONY INHIBITION-FACTOR (M-CIF) FROM CHO MICROCARRIER PERFUSION CULTURES

Monocyte-colony inhibition factor (M-CIF) was produced in microcarrier perfusion cultures from engineered Chinese hamster ovary (CHO) cells. Three and fifteen liter microcarrier perfusion bioreactors equipped w ith internal spin filters were operated for over two months. Approxima tely 60 L, and 300 L of culture filtrate were harvested from the 3L an d 15L, microcarrier perfusion bioreactors respectively. During the per fusion operation, cell density reached 2-6 x 10(6) cells/ml. Important ly, stable expression of M-CIF from the CHO cells under non-selection condition was maintained at a level of 4-10 mg/L. Specific productivit y was maintained at 1.8-3.4 mg/billion cells/day. The ability of the r ecombinant CHO cells to migrate from microcarrier to microcarrier unde r our proprietary HGS-CHO-3 medium greatly facilitated microcarrier cu lture scale-up and microcarrier replenishment. Future directions for m icrocarrier perfusion system scale-up and process development are high lighted.