Production of Antitumor Mononuclear Blood Cells in Tumor-Bearing Mice by Interferon-αA/D Therapy

Abstract

Administration of human interferon-alpha A/D (IFN-alpha A/D) to Meth A fibrosarcoma-bearing mice produced mononuclear blood cells with antiproliferation activity that were able to suppress Meth A growth in vitro. Their production depended on IFN doses and administration intervals. They were short-lived since antiproliferation activity was not detectable in mononuclear cells 2 days after cessation of IFN administration, although it was detectable as long as IFN administration continued. A similar production of antiproliferative mononuclear blood cells by IFN was achieved in tumor-free as well as in tumor-bearing mice, indicating no deleterious effect of the growing tumor on the production of these cells. IFN-induced antiproliferation activity was not tumor-specific since mononuclear blood cells of IFN-administered mice bearing either Meth A and Meth 1, another antigenically distinct fibrosarcoma, suppressed the in vitro growth of both Meth A and Meth 1 cells. T cells were not involved in the in vivo production of antiproliferative mononuclear blood cells by IFN therapy because the cells with this activity were produced in vivo in Meth A-bearing athymic mice and also in Meth A-bearing mice with reduced T-cell populations by the treatment with alpha mouse thymocyte globulin. T cells were not involved in their antiproliferation activity either, since the in vitro T-cell depletion of mononuclear cells did not diminish this antiproliferation activity. Because mononuclear cells surviving the in vitro T cell depletion were positive for AcM.1 (an epitope of activated macrophage) and also because the alpha Mac-1 antibody completely abolished their in vitro antiproliferation activity, this led us to conclude that it was activated monocytes in blood that were produced by IFN in a T-cell-independent fashion and that these monocytes were the cells responsible for the observed in vitro antiproliferation activity.