In a reproducible murine model of liver
metastases, it was demonstrated that liposomal
muramyl dipeptide (MDP) as an adjuvant
therapy reduces and prevents the development of
metastases. C26
colon adenocarcinoma cells were injected into the spleen (5 x 10(4) cells per mouse) of syngeneic BALB/c mice. On day 3, the spleen was removed to prevent a large
tumor burden in the spleen. On day 17, 100% of the mice had developed
tumor foci in the liver. Liposomal MDP treatment consisted of the i.v. or i.p. administration of 1 mumol of liposomal
lipid containing 5 micrograms of MDP per mouse for ten consecutive days. When
therapy was initiated two days after
tumor cell inoculation, the number of
metastases that had developed on day 17 was strongly reduced compared to control mice. Approximately 20% of the mice were free of liver
metastases. Initiation of
therapy two days prior to
tumor cell inoculation enhanced the effect significantly: about 45% of the mice were free of
metastases on day 17. The treatment protocol for survival studies was slightly different; liposomal MDP was administered on the first six consecutive days followed by administration twice weekly, through day 24. Control mice died between day 21 and 33 after
tumor cell inoculation, whereas liposomal MDP treated mice died between day 26 and 46 with 1 out of 25 mice surviving for more than 120 days. The mortality of the liposomal MDP treated mice that were free of liver
metastases was caused by a local
tumor at the site of operation.(ABSTRACT TRUNCATED AT 250 WORDS)