A study on the antitumor effect of the combined local administration of interleukin-2 and interferon-β in a murine model

Abstract

This study assessed the antitumor effects of local administration of interleukin-2 (IL-2) and/or interferon-β on mouse-syngeneic transplantable plasmacytoma X 5563. When the tumor reached a palpable size of 5 to 10mm in diameter, the mice were divided into four groups: IL-2 alone, IFN-β alone, a combination of IL-2 and IFN-β, and a control group. 35, 000 JRU of IL-2 and 100, 000 U of IFN-β were administered intratumorally every day for ten days. Tumor growth was inhibited partially in the IL-2 alone group and in the IFN-β alone group. The tumor disappeared in only 1 of 13 mice in the IFN-β alone group and in none of the mice in the IL-2 alone group. On the other hand, the combination of IL-2 and IFN-β produced a significant reduction in tumor size and the tumor disappeared in 24 of 26 mice. The rate of metastasis to the inguinal and/or axillary lymph nodes was 33.3% in the IL-2 alone group, 38.5% in the IFN-β alone group, and only 7.7% in the group receiving a combination of IL-2 and IFN-β. Compared with the control group, treatment with IL-2 or IFN-β alone did not prolong survival whereas survival was significantly longer in the group given combined treatment than the other three groups.
Histologically, infiltration of many mononuclear cells and neutrophilic leucocytes was seen around tumor tissues only in the combination group. The mononuclear cells reacted with Thy 1.2 and Lyt-2 antigen predominantly.
Although NK activities of spleen cells were enhanced significantly in the three experimental groups compared with the control group, LAK activities were not enhanced. Cytotoxic activities against X 5563 were induced only in the combination group. In vivo and in vitro studies using the anti asialo-GM 1 antibody revealed that, since asialo-GM 1 negative cells had cytotoxic activities against X 5563, the involvement of NK cells in the antitumor effect of combined treatment with IL-2 and IFN-β was minimal. The administration of IL-2 and IFN-β augmented MHC class I antigen expression on X 5563 cells compared witht the primary cells.
These facts suggest that the antitumor effect of combined treatment with IL-2 and IFN-βinvolves T cells rather than NK cells. Combination therapy with IL-2 and IFN-β seems to be a new useful immunotherapy for oral cancer.