Intravesical liposomal muramyl tripeptide phosphatidylethanolamine treatment of human bladder carcinoma growing in nude mice.
The present study evaluated the in vivo activity of synthetic lipophilic muramyl tripeptide phosphatidylethanolamine (MTP-PE) when encapsulated into liposomes (phosphatidylcholine-phosphatidylserine, 7:3 molar ratio) and administered intravesically to athymic nude mice with human transitional cell carcinoma 253J-V cells growing in their bladder. Intravesical liposome-MTP-PE was effective in eradicating the human tumors implanted orthotopically in nude mice. Following therapy, activated macrophages were found in the bladders of liposome-MTP-PE-treated mice but not in control mice. In vitro activation of murine macrophages with liposome-MTP-PE increased their cytotoxicity against the 253J-V cell line used in these experiments. This effect was enhanced by cotreatment with interferon-gamma (IFN-gamma). Furthermore, cotreatment of macrophages with both liposome-MTP-PE and IFN-gamma resulted in the secretion of both tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Liposome-encapsulated MTP-PE shows promise as an effective therapeutic agent for bladder carcinoma.
Dinney
C P
CP
Department of Cell Biology, University of Texas-M.D. Anderson Cancer Center, Houston 77030, USA.
Tanguay
S
S
Bucana
C D
CD
Eve
B Y
BY
Fidler
I J
IJ
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000283:Administration, Intravesical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D017690:Cell Transplantation; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008081:Liposomes; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010714:Phosphatidylethanolamines / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine