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 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.
Worth
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Department of Pediatrics, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Jia
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SF
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Kleinerman
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D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D002277:Carcinoma / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008081:Liposomes; D016215:Macrophage-Activating Factors / Q000096:biosynthesis / Q000235:genetics; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012516:Osteosarcoma / Q000276:immunology / Q000473:pathology; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010715:Phosphatidylglycerols / Q000494:pharmacology*; D012512:Sarcoma, Ewing / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007378:Interleukins; D008081:Liposomes; D016215:Macrophage-Activating Factors; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D014409:Tumor Necrosis Factor-alpha; C071672:disaccharide tripeptide; D000119:Acetylmuramyl-Alanyl-Isoglutamine