Antitumor reactivity induced by liposomal MTP-PE in a liver metastasis model of colon cancer in the rat.
The antitumor effects of muramyl tripeptide phosphatidylethanolamine, incorporated within the lipophilic phase of liposomes (lipMTP-PE) were studied using a model of liver metastasis of colon cancer in the rat. Intravenous immunotherapy with lipMTP-PE, when started 2 days before the inoculation of tumor cells and given twice a week, significantly reduced subsequent tumor growth in the liver. The main effect of treatment appeared to be a substantial local increase in the number of tumoricidal macrophages and lymphocytes. Tumor cell lysis by isolated macrophages in vitro, however, appeared not to be elevated above the level triggered by tumor growth alone. Therefore, the observed therapeutic effect of lipMTP-PE probably results from a combination of (1) an increase in the number of cytotoxic macrophages at the onset of metastatic growth in the liver, thus increasing the probability of lethal contacts between tumoricidal effectors and tumor cells and (2) indirect effects of lipMTP-PE, via the induction of cytokine production by liver macrophages, leading to increased numbers and/or activity of cytotoxic lymphocytes and natural killer cells.
Thomas
K
K
Groningen Institute for Drug Studies (GIDS), Department of Physiological Chemistry, University of Groningen, The Netherlands.
Nijenhuis
A M
AM
Dontje
B H
BH
Daemen
T
T
Scherphof
G L
GL
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D003602:Cytotoxicity, Immunologic; D007150:Immunohistochemistry; D007167:Immunotherapy; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008264:Macrophages / Q000166:cytology; D008297:Male; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008081:Liposomes; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine