Discrimination between nonmalignant and malignant cells by combinations of IFN-gamma and IFN-alpha/beta.

Combination treatment with interferon (IFN)-gamma and either IFN-alpha or IFN-beta synergistically enhances (potentiates) the anticellular effects of the IFNs. IFNs have been shown to have anticellular activity against normal as well as malignant cells. To study the relative effectiveness of IFN's anticellular activity against nonmalignant and malignant cells in the mouse system, two paired sets of nonmalignant/malignant cells (JB-1/JB-8; D-1/D-11a) were studied using 3-day kinetics of cell growth experiments. Treatment of the nonmalignant cells with IFN-gamma or IFN-alpha/beta employed separately had little or no effect on the growth of the cells at the IFN concentrations employed. Combination IFN treatment had only a slight effect on the growth of these cells. Treatment of the malignant cells with IFN-gamma or IFN-alpha/beta employed separately had low levels of effect on the growth of the cells. In contrast, treatment of these malignant cells with combined IFN-gamma and IFN-alpha/beta had a very marked anticellular effect, dramatically showing the growth of, or even killing, the malignant cells. These observations appeared to be independent of the growth status of the cells, since stationary-phase and log-phase malignant cells maintained their relatively greater sensitivity to the IFNs. Thus, IFN treatment, particularly combination IFN treatment, had a differential effect on the growth of the paired sets of nonmalignant and malignant cells and appeared to sharply differentiate between nonmalignant and malignant cells.