Synergistic antiproliferative effects of human recombinant α54–or βser-interferon with β–interferon on human cell lines of various histogenesis

The antiproliferative effects of human interferon (IFN), IFN-γ, IFN-a54, and IFN-βser, 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-γ to either IFN-α54 or IFN-βser, 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-γ but not to IFN-βser, one was relatively resistant to IFN-βser, but not to IFN-γ, and th'e remainder were resistant to both IFN-γ and IFN-βser or lFN-α54. The addition of IFN-a54 to IFN-βser. in the SKCO 1 cell line resulted in an antagonistic interaction. Timing experiments with RT112 cells indicate that IFN-7 and IFN-βser, 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. copyright.