Activation of Tumoricidal Properties in Human Blood Monocytes by Liposomes Containing Lipophilic Muramyl Tripeptide1

Peripheral blood monocytes were isolated from normal human donors by separation on a continuous Percoli gradient and adherence to yield preparations of blood monocytes with a high degree of purity (> 99%). The monocytes were incubated in vitro with medium alone or with multilamellar liposomes that contained either a lipophilic derivative of muramyl dipeptide, muramyl tripeptide (MTP-PE), or medium. The cytotoxic properties of the monocytes were assessed by an in vitro radioisotope release assay against various allogeneic targets. Monocytes that have phagocytosed liposomes containing MTP-PE were rendered tumoricidal. These monocytes lysed cells of three different tumorigenic lines but not cells of two nontumorigenic lines. The ability of MTP-PE-activated human blood monocytes to recognize and selectively lyse neoplastic cells was also demonstrated under cocultivation conditions. We conclude that human blood mono cytes can be rendered tumoricidal after interaction with lipo somes containing MTP-PE.