Inhibition in mice of experimental metastasis of B16 melanoma by the synthetic lipid A-subunit analogue GLA-60.

Antimetastatic effects of the monosaccharic lipid A-subunit analogue GLA-60 against B16-F10 melanomas were investigated. Intravenous injection of 10 micrograms GLA-60 one day or two days before transplantation of 10(5) melanoma cells resulted in a significant decrease in the number of melanoma colonies metastasized into the lung. Intramuscular injection was also effective. Oral administration as well as intraperitoneal and subcutaneous administrations of 100 micrograms GLA-60 were also effective in preventing metastasis of the melanoma. However, these prophylactic effects of GLA-60 on the metastasis were diminished in mice which had been pre-treated with anti-asialo GM1 serum; on the other hand, prophylaxis was not affected in mice pre-treated with anti-Mac 1 antibody. These results suggest that asialo GM1 positive cells, probably natural killer cells, but not macrophages, participate as effector cells in depressing metastasis of the melanoma cells into the lung. In addition, GLA-60 also showed therapeutic potency in depressing metastasis, under a defined condition. The antimetastatic effect of GLA-60 was compared with other immunomodulators.