Engineered measles virus Edmonston strain used as a novel oncolytic viral system against human neuroblastoma through a CD46 and nectin 4-independent pathway

Cancer Lett. 2012 Dec 28;325(2):227-37. doi: 10.1016/j.canlet.2012.07.008. Epub 2012 Jul 13.

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumor in children. In this study, we investigated the potential antitumor capability of the engineered Edmonston strain of the carcinoembryonic antigen-expressing measles virus (MV-CEA) against human NB. The infection of a variety of NB cell lines, including SK-N-SH, SMS-KCNR, and primary NB cells, resulted in significant cytopathic effects. None of the NB cell lines showed an overexpression of the measles virus receptor CD46 and nectin 4, but the cell lines did support robust viral replication. The efficacy of this approach was examined in murine SK-N-SH xenograft models. Flow cytometry and TUNEL assays indicated an apoptotic mechanism of cell death. In summary, MV-CEA has potent therapeutic efficacy against NB mediated by a CD46- and nectin 4-independent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoembryonic Antigen / genetics
  • Cell Adhesion Molecules / analysis
  • Cell Line, Tumor / pathology
  • Cell Line, Tumor / transplantation
  • Cell Line, Tumor / virology
  • Child, Preschool
  • Cytopathogenic Effect, Viral
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / virology
  • Genetic Vectors / therapeutic use
  • Giant Cells
  • Humans
  • Male
  • Measles virus / physiology*
  • Membrane Cofactor Protein / analysis
  • Mice
  • Mice, Nude
  • Mice, SCID
  • Neuroblastoma / therapy*
  • Oncolytic Virotherapy*
  • Receptors, Virus / analysis
  • Tumor Stem Cell Assay
  • Viral Tropism
  • Virus Replication
  • Xenograft Model Antitumor Assays

Substances

  • CD46 protein, human
  • Carcinoembryonic Antigen
  • Cell Adhesion Molecules
  • Membrane Cofactor Protein
  • Receptors, Virus
  • NECTIN4 protein, human