Potent in situ activation of murine lung macrophages and therapy of melanoma metastases by systemic administration of liposomes containing muramyltripeptide phosphatidylethanolamine and interferon gamma.
Mouse alveolar macrophages (AM) were rendered tumoricidal after the intravenous administration of liposomes containing muramyl tripeptide phosphatidylethanolamine (MTP-PE), a lipophilic derivative of muramyl dipeptide. The addition of recombinant mouse interferon gamma (r-IFN-gamma) to the liposomes significantly potentiated this effect. This potentiation was also observed in therapeutic studies of mice bearing well-established spontaneous lung melanoma metastases. Multiple intravenous injections of liposomes containing both MTP-PE and r-IFN-gamma resulted in 70% survival in one group treated for small lung metastases and 50% in another group treated for large lung metastases. These data demonstrate that the presentation of r-IFN-gamma and MTP-PE in liposomes is more efficient in inducing the destruction of metastases than either agent administered alone.
Fidler
I J
IJ
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston.
Fan
D
D
Ichinose
Y
Y
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004337:Drug Carriers; D007371:Interferon-gamma / Q000008:administration & dosage*; D008081:Liposomes; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008207:Lymphatic Metastasis; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology; D008546:Melanoma, Experimental / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010714:Phosphatidylethanolamines / Q000008:administration & dosage*; D011994:Recombinant Proteins
D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma