ImmTher, a lipophilic disaccharide derivative of muramyl dipeptide, up-regulates specific monocyte cytokine genes and activates monocyte-mediated tumoricidal activity

ImmTher, a liposome-encapsulated lipophilic disaccharide tripeptide derivat ive of muramyl dipeptide, previously showed activity against liver and lung colorectal metastases in a phase I trial. The purpose of the current studi es was to investigate whether ImmTher could up-regulate specific cytokine g ene expression and protein production, as well as activate the tumoricidal or cytostatic activity of human monocytes. ImmTher induced the expression a nd production of interleukin(IL)-1 alpha IL-1 beta, IL-6, IL-8, IL-12, macr ophage chemotactic and activating factor, and tumor necrosis factor a but n ot IL-2 or IL-10. Cytostatic or cytotoxic monocyte activity was stimulated against human Ewing's sarcoma, osteosarcoma, and melanoma cells but not bre ast cancer cells. Production and secretion of these cytokine proteins may p lay a role in the antitumor activity of ImmTher.