Antitumor effect to IL-12 administration into the portal vein on murine liver metastasis.

ABSTRACT

BACKGROUND/PURPOSE: Interleukin (IL)-12 has been shown to possess potent antitumor activity, and an antitumor effect of systemic IL-12 administration has been reported in liver metastasis models. METHODS: In this study, we examined the usefulness of local IL-12 administration into the portal system in the treatment of liver metastasis. First, we confirmed the antitumor effect of recombinant IL-12 (rIL-12) on MC-38 tumors in an intracutaneous model. In the murine liver metastasis model, 1 x 10(5) of MC-38 cells were injected into the portal vein on day 0, and the spleen was transpositioned subcutaneously for administration of rIL-12 continually into the portal system. From days 3 to 7, 0.1 micro g rIL-12 was administered intraperitoneally or intrasplenicly, while Hanks' Balanced Salf Solution (HBSS) was injected intrasplenicly in the control group. RESULTS: The liver weight in the rIL-12 intraperitoneal treatment group (1.88 +/- 0.37 g) and that in the rIL-12 intrasplenic treatment group (1.43 +/- 0.21 g) were significantly less than that in the HBSS group (2.86 +/- 0.74 g; P < 0.05). The numbers of metastatic nodules in the rIL-12 intraperitoneal treatment group (22.3 +/- 17.1) and in the rIL-12 intrasplenic treatment group (12.4 +/- 13.8) were significantly less than that in the HBSS group (137.1 +/- 44.9; P < 0.05). Complete regression of the tumor was observed in one of six mice in the rIL-12 intrasplenic treatment group. This antitumor effect of rIL-12 on MC-38 liver metastasis was not observed in interferon (IFN)-gamma knockout mice. Intraportal administration of IL-12-transduced fibroblasts, which were syngeneic to C57BL/6 mice, had an antitumor effect in the MC-38 liver metastasis model. CONCLUSIONS: These results suggested that the local administration of IL-12 into the portal system would be a useful strategy for the treatment of liver metastasis.