title: Activation of tumoricidal properties in monocytes from cancer patients following intravenous administration of liposomes containing muramyl tripeptide phosphatidylethanolamine.
abstract: This study examined the antitumor properties of blood monocytes isolated from patients undergoing a phase I trial with liposomes containing muramyl tripeptide phosphatidylethanolamine (L-MTP-PE). Peripheral blood monocytes were isolated from 28 patients receiving twice weekly i.v. injections of escalating doses of L-MTP-PE. Monocytes were harvested before therapy and at various times during the 9-week treatment period. Activation of monocyte-mediated tumorilytic activity was found in 24 of the 28 patients at some time during treatment. Whereas the maximum tolerated dose of L-MTP-PE was 4-6 mg/m2, the optimal biological dose in terms of macrophage activation was 0.5-2.0 mg/m2. The spontaneous secretion of interleukin 1 from monocytes isolated pre- and postinfusion was monitored in two patients. In both patients interleukin 1 secretion correlated with the cytotoxic activity of the monocytes. We conclude that the systemic administration of L-MTP-PE can render the blood monocytes of cancer patients tumor cytotoxic. Since L-MTP-PE is an immunomodulator devoid of direct antiproliferative effects on tumor cells, the data suggest that future clinical trials be conducted using the optimal biological dose rather than the maximum tolerated dose.
authors: Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors: E S
authors: ES
authors: Kleinerman
authors: J L
authors: JL
authors: Murray
authors: J S
authors: JS
authors: Snyder
authors: J E
authors: JE
authors: Cunningham
authors: I J
authors: IJ
authors: Fidler
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000502:physiology; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D014677:Pharmaceutical Vehicles; D010714:Phosphatidylethanolamines / Q000008:administration & dosage*
chemical_list: D007375:Interleukin-1; D014677:Pharmaceutical Vehicles; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine