Chemical conjugation of muramyl dipeptide and paclitaxel to explore the combination of immunotherapy and chemotherapy for cancer

Glycoconj J. 2008 Jul;25(5):415-25. doi: 10.1007/s10719-007-9095-3. Epub 2007 Dec 27.

Abstract

Paclitaxel (Taxol) conjugated to muramyl dipeptide (MDP) is described. Biological testing showed that the conjugation of MDP at 2'-O-paclitaxel (2'- O -MTC-01) not only has antitumor activity, but also have immunoenhancement capacity. Compared with paclitaxel or MDP alone or with a mixture of paclitaxel + MDP, 2'- O -MTC-01 significantly increases the production and expression of TNF-alpha and IL-12 from mouse peritoneal macrophages, which demonstrates a synergism of MDP and paclitaxel in one conjugated molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / chemical synthesis
  • Acetylmuramyl-Alanyl-Isoglutamine / chemistry
  • Acetylmuramyl-Alanyl-Isoglutamine / therapeutic use*
  • Animals
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Drug Therapy, Combination
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunotherapy*
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Neoplasms / drug therapy*
  • Paclitaxel / chemical synthesis
  • Paclitaxel / chemistry
  • Paclitaxel / therapeutic use*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Acetylmuramyl-Alanyl-Isoglutamine
  • Paclitaxel