The antimetastatic effects of
MDP-Lys(L18), a lipophilic derivative of
muramyl dipeptide (MDP), against three different types of highly metastatic murine tumour cells, B16-BL6
melanoma, colon 26-M3.1
carcinoma and L5178Y-ML25 T
lymphoma, were examined in C57BL/6, Balb/c and CDF1 mice, respectively. The administration of 100 micrograms of
MDP-Lys(L18) 2 or 4 days before tumour inoculation led to a significant decrease in lung
metastasis of B16-BL6
melanoma or colon 26-M3.1
carcinoma cells.
MDP-Lys(L18) was also effective in the inhibition of liver
metastasis of L5178Y-ML25
lymphoma cells by administration 2 or 4 days before tumour inoculation. The prophylactic effect of 100 micrograms of
MDP-Lys(L18) on tumour
metastasis was evident for the different administration routes, i.e. subcutaneous, intravenous or intranasal injection, or
oral administration. It is of prime interest that
oral administration of 1 mg of
MDP-Lys(L18) induced a significant decrease in lung
metastasis of B16-BL6
melanoma cells. Administration of
MDP-Lys(L18) 4 days before assay led to induction of tumoricidal activity by peritoneal macrophages and growth inhibition by the sera against B16-BL6 or L929 cells. When
MDP-Lys(L18) was subcutaneously administered five times after tumour inoculation to test
therapeutic effect in an experimental and spontaneous
metastasis model using B16-BL6
melanoma, the consecutive administrations of
MDP-Lys(L18) significantly inhibited lung
metastasis in tumour-bearing mice. These results suggest that
MDP-Lys(L18) is able to enhance host resistance to reduce tumour
metastasis and is a potent immunomodulating agent which may be applied prophylactically or therapeutically for the treatment of
cancer metastasis.