Peripheral blood monocytes were isolated from normal human donors by separation on a continuous Percoll 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 monocytes can be rendered tumoricidal after interaction with liposomes containing MTP-PE.

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Research supported in part by the National Cancer Institute, Department of Health and Human Services, under Contract N01-CO-23909 with Litton Bionetics, Inc.

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