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

Abstract	ImmTher, a liposome-encapsulated lipophilic disaccharide tripeptide derivative of muramyl dipeptide, previously showed activity against liver and lung colorectal metastases in a phase I trial. The purpose of the current studies was to investigate whether ImmTher could up-regulate specific cytokine gene expression and protein production, as well as activate the tumoricidal or cytostatic activity of human monocytes. ImmTher induced the expression and production of interleukin(IL)-1alpha IL-1beta, IL-6, IL-8, IL-12, macrophage chemotactic and activating factor, and tumor necrosis factor alpha but not IL-2 or IL-10. Cytostatic or cytotoxic monocyte activity was stimulated against human Ewing's sarcoma, osteosarcoma, and melanoma cells but not breast cancer cells. Production and secretion of these cytokine proteins may play a role in the antitumor activity of ImmTher.
Authors	L L Worth, S F Jia, T An, E S Kleinerman
Journal	Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 48 Issue 6 Pg. 312-20 (Sep 1999) ISSN: 0340-7004 [Print] Germany
PMID	10473806 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Adjuvants, Immunologic Cytokines Interleukins Liposomes Macrophage-Activating Factors Phosphatidylcholines Phosphatidylglycerols Tumor Necrosis Factor-alpha disaccharide tripeptide Acetylmuramyl-Alanyl-Isoglutamine
Topics	Acetylmuramyl-Alanyl-Isoglutamine (analogs & derivatives, pharmacology) Adjuvants, Immunologic (pharmacology) Breast Neoplasms (immunology, pathology) Carcinoma (immunology, pathology) Cells, Cultured Cytokines (biosynthesis, genetics) Cytotoxicity, Immunologic (drug effects) Gene Expression Regulation (drug effects) Humans Interleukins (biosynthesis, genetics) Liposomes Macrophage-Activating Factors (biosynthesis, genetics) Melanoma (immunology, pathology) Monocytes (drug effects, immunology, metabolism) Osteosarcoma (immunology, pathology) Phosphatidylcholines (pharmacology) Phosphatidylglycerols (pharmacology) Sarcoma, Ewing (immunology, pathology) Tumor Cells, Cultured (immunology) Tumor Necrosis Factor-alpha (biosynthesis, genetics)

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