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

Cancer Immunol Immunother. 1999 Sep;48(6):312-20. doi: 10.1007/s002620050580.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives*
  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
  • Adjuvants, Immunologic / pharmacology*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Carcinoma / immunology
  • Carcinoma / pathology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / genetics*
  • Cytotoxicity, Immunologic / drug effects*
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Liposomes
  • Macrophage-Activating Factors / biosynthesis
  • Macrophage-Activating Factors / genetics
  • Melanoma / immunology
  • Melanoma / pathology
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / metabolism
  • Osteosarcoma / immunology
  • Osteosarcoma / pathology
  • Phosphatidylcholines / pharmacology*
  • Phosphatidylglycerols / pharmacology*
  • Sarcoma, Ewing / immunology
  • Sarcoma, Ewing / pathology
  • Tumor Cells, Cultured / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Interleukins
  • Liposomes
  • Macrophage-Activating Factors
  • Phosphatidylcholines
  • Phosphatidylglycerols
  • Tumor Necrosis Factor-alpha
  • disaccharide tripeptide
  • Acetylmuramyl-Alanyl-Isoglutamine