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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives*
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Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
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Adjuvants, Immunologic / pharmacology*
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Breast Neoplasms / immunology
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Breast Neoplasms / pathology
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Carcinoma / immunology
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Carcinoma / pathology
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Cells, Cultured
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Cytokines / biosynthesis
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Cytokines / genetics*
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Cytotoxicity, Immunologic / drug effects*
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Gene Expression Regulation / drug effects*
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Humans
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Interleukins / biosynthesis
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Interleukins / genetics
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Liposomes
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Macrophage-Activating Factors / biosynthesis
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Macrophage-Activating Factors / genetics
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Melanoma / immunology
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Melanoma / pathology
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Monocytes / drug effects*
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Monocytes / immunology
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Monocytes / metabolism
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Osteosarcoma / immunology
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Osteosarcoma / pathology
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Phosphatidylcholines / pharmacology*
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Phosphatidylglycerols / pharmacology*
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Sarcoma, Ewing / immunology
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Sarcoma, Ewing / pathology
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Tumor Cells, Cultured / immunology
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / genetics
Substances
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Adjuvants, Immunologic
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Cytokines
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Interleukins
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Liposomes
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Macrophage-Activating Factors
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Phosphatidylcholines
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Phosphatidylglycerols
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Tumor Necrosis Factor-alpha
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disaccharide tripeptide
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Acetylmuramyl-Alanyl-Isoglutamine