Antitumor activity of alpha-galactosylceramide, KRN7000, in mice with EL-4hepatic metastasis and its cytokine production

Liver metastasis of primary tumor is a clinically major problem. KRN7000, a n alpha-galactosylceramide, significantly augments natural killer (NK) acti vity of spleen cells and shows strong antitumor activity in mice with lung metastasis of melanoma B16 cells. To test whether KRN7000 has an antitumor activity in mice with hepatic metastasis of tumors, we examined the effect of KRN7000 on NK activity of hepatic monomuclear cells (MNC) and the antitu mor activity in mice with liver metastasis of EL-4 cells. The in vivo admin istration of KRN7000 significantly augmented NK activity of hepatic MNC and inhibited tumor growth of EL-4 cells in the liver more markedly than chemo therapeutic agents. leading to a relatively high rate of cured mice. In add ition, it appeared that the KRN7000 treatment is effective in mice with est ablished EL-4 tumors. Moreover, we found that KRN7000 can produce significa nt amounts of interleukin 2 (IL-2), IL-4, IL-12, and interferon-gamma in a dose-dependent manner. These results suggest that KRN7000 will be useful fo r the treatment of cancer liver metastasis.