Isolation of tumoricidal macrophages from lung melanoma metastases of mice treated systemically with liposomes containing a lipophilic derivative of muramyl dipeptide

The systemic administration of multilamellar liposomes - composed of phosphatidylcholine and phosphatidylserine (7:3 mol ratio), containing the immunomodulator, muramyl tripeptide phosphatidylethanolamine (MTP-PE) - into C57BL/6N mice bearing the syngeneic B16-BL6 melanoma was associated with the eradication of spontaneous lung and lymph node metastases. Immunofluorescence and electron microscopic analyses revealed that 24 hours after the tumor-bearing mice were given iv injections of liposomes, 15% of the alveolar macrophages and 5% of the metastasis-associated macrophages contained phagocytosed liposomes. However, only macrophages isolated from lungs or metastases of mice given injections of liposomes containing MTP-PE (treatment success), but not macrophages from mice treated with empty liposomes (treatment failure), were tumoricidal against the target cells in vitro. These data provide direct evidence that the regression of established metastases, after treatment of tumor-bearing mice with liposomes containing MTP-PE, was associated with tumoricidal macrophages residing within the metastases.