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By the spring of 1981, Fidler and Poste and their co-workers had demonstrated that monocytes could be activated to become tumoricidal after incubation with liposomes containing monocyte/macrophage activating agents (Fidler, 1975; Fidler et al., 1976). These same phosphatidylcholine (PC), phosphatidylserine (PS) liposomes containing muramyl dipeptide (MDP) or one of its derivatives could eradicate spontaneous metastases in mice (Fidler et al., 1981). Furthermore, no toxicity is observed when liposomes are administered intravenously to dogs and mice (Hart et al., 1981).

The capacity for metastatic spread can be reasonably regarded as the single most important characteristic of malignant tumors. Metastasis as simply defined is the loss of contiguity between a tumor cell or clumps of tumor cells and the primary lesion followed by successful transfer to and growth at a site spatially separate from the original tumor. The overall process can be viewed as a series of sequential events representing complex interactions between the tumor cell and the host (Figure 1). Following the release of tumor cells from the primary tumor they are transported passively (dissemination) in the circulatory system. In order to successfully colonize the distant metastatic site the tumor cell must first arrest (implantation) and then invade (extravasation) through the vessel wall. The process of arrest and extravasation are the most critical steps in the metastatic cascade for circulating tumor cells.