Treatment regimen and host T-cell-dependent therapeutic effect of interferon in mouse solid tumors

Abstract

A highly purified hybrid human interferon (IFN)-alpha A/D, was used to define optimum treatment regimens for Meth A fibrosarcoma intradermally inoculated in syngeneic BALB/c mice. Treatments from the sixth day post-tumor inoculation were most effective, and 10 consecutive injections of IFN completely suppressed the tumor growth for a prolonged time without recurrence after the last injection of IFN. Intraperitoneal and intravenous injections were similarly effective. The therapeutic effect of IFN was abrogated by the injection of rabbit alpha-mouse thymocyte globulin but not normal rabbit globulin. The therapeutic effect of IFN was much poorer in BALB/c nu/nu mice, which are athymic and defective in T-cell immunity, than in BALB/c +/+ mice. Mice in which Meth A growth was completely suppressed by IFN were refractory to Meth A, but not Meth 1 tumor, another antigenically distinct fibrosarcoma, whereas mice in which Meth 1 growth was suppressed completely by IFN were refractory to Meth 1 but not Meth A tumor. These three findings suggest that the therapeutic effect of IFN depended on host T-cell immunity and that tumors were eventually eliminated by tumor-selective antitumor immunity provoked during IFN therapy. Under the present experimental conditions, the direct anticellular activity of IFN was presumed to contribute very little to the therapy for solid tumors, since the therapeutic effect of IFN on three different solid tumors was not correlated with their in vitro sensitivity to this substance: Colon 26, which was as sensitive to IFN as Meth A in the in vitro antiproliferation, responded most poorly to IFN therapy, while Meth A and Meth 1 responded similarly well to IFN therapy, although there was more than a 2500 times difference in their in vitro IFN sensitivity.