Synergistic antiproliferative effects of human recombinant alpha 54- or beta ser-interferon with gamma-interferon on human cell lines of various histogenesis.

The antiproliferative effects of human interferon (IFN), IFN-gamma, IFN-alpha 54, and IFN-beta ser, alone and in combination, were assessed on 10 human cell lines. All IFNs were produced by recombinant technology and purified to homogeneity. In all cell lines except one, the addition of IFN-gamma to either IFN-alpha 54 or IFN-beta ser resulted in a synergistic antiproliferative effect, regardless of individual IFN sensitivities or tissue of origin. The only exception was a normal diploid fibroblast cell in which an additive antiproliferative effect occurred with combination IFN treatment. A malignant fibrosarcoma cell line of similar mesenchymal origin demonstrated a synergistic antiproliferative effect. One cell line was sensitive to both type I and type II IFN alone. Three cell lines were relatively resistant to IFN-gamma but not to IFN-beta ser, one was relatively resistant to IFN-beta ser but not to IFN-gamma, and the remainder were resistant to both IFN-gamma and IFN-beta ser or IFN-alpha 54. The addition of IFN-alpha 54 to IFN-beta ser in the SKCO 1 cell line resulted in an antagonistic interaction. Timing experiments with RT112 cells indicate that IFN-gamma and IFN-beta ser need not be in the media at the same time for the synergistic effect to occur. Combinations of type I and type II IFN thus resulted in synergistic antiproliferative effect for transformed human cells of various histogenesis, including some with a relative resistance to one or both IFN types.