Systemic Activation of Macrophages by Liposomes Containing Muramyltripeptide Phosphatidylethanolamine for therapy of Cancer Metastasis

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Abstract
The heterogeneous response of metastases to conventional therapy is a major cause of failure in cancer treatment. Evidence that activated macrophages can recognize and destroy neoplastic cells in vitro without regard to their phenotypic diversity has stimulated efforts to develop effective approaches to the activation of macrophages in situ. Systemic administration of liposomes containing immunomodulators activates macrophages in situ and augments host destruction of spontaneous metastases. Liposomes are a useful carrier system for the transport of agents to phagocytic cells in vivo. Once in the circulation, liposomes are cleared by phagocytic cells, and this passive localization provides an effective mechanism for targeting liposome-entrapped materials, such as muramyltripeptide phosphatidylethanolamine (MTP-PE), to macrophages. Macrophage destruction of metastases in vivo is significant, provided that the total tumor burden at start of treatment is minimal. For this reason, we advocate using chemotherapy or radiotherapy first to reduce the tumor burden in patients with metastases. Tumoricidal macrophages that can differentiate neoplastic from bystander nonneoplastic cells are then used to destroy the few tumor cells that escape destruction by conventional therapeutic methods.