Liposomal muramyl dipeptide therapy of experimental M5076 liver metastases in mice.
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| Abstract |
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.
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| Authors | N C Phillips, M S Tsao |
| Journal | Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 33 Issue 2 Pg. 85-90 ( 1991) ISSN: 0340-7004 [Print] Germany |
| PMID | 2036662 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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