Liposomal muramyl dipeptide therapy of experimental M5076 liver metastases in mice.
The effectiveness of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) or of liposomes containing a lipophilic MDP derivative, MDP-glyceroyldipalmitate MDP-GDP in inhibiting the growth of M5076 reticulum cell sarcoma liver metastases in C57BL/6 mice has been determined. MDP (100 micrograms) or liposomal MDP-GDP (2.5 mumol containing 1 microgram) were equally effective in inhibiting liver metastatic growth when given as a single treatment 3 days before tumor cell injection. Therapeutic treatment, initiated 3 days after tumor cell injection and continued for a period of 2 weeks, failed to inhibit metastatic growth. Activation of thioglycollate-elicited peritoneal macrophages or Kupffer cells in vitro with MDP or liposomal MDP-GDP resulted in the expression of tumoricidal activity against M5076 tumor cells. Adoptive cellular therapy with four injections of 2 x 10(6) macrophages was ineffective: activation of the macrophages with either MDP or liposomal MDP-GDP prior to injection was effective in inhibiting liver metastatic growth. Incorporation of the macrophage toxin dichlorodimethylene diphosphonate within liposomes containing MDP-GDP abolished the ability of such liposomes to induce macrophage or Kupffer cell tumoricidal activity in vitro as well as the antitumor activity when administered 3 days before tumor cell challenge.
Phillips
N C
NC
Montreal General Hospital Research Institute, Quebec, Canada.
Tsao
M S
MS
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D004337:Drug Carriers; D016219:Immunotherapy, Adoptive; D007728:Kupffer Cells / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000556:secondary; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL
D004337:Drug Carriers; D008081:Liposomes; D000119:Acetylmuramyl-Alanyl-Isoglutamine