Effective radiovirotherapy for malignant gliomas by using oncolytic measles virus strains encoding the sodium iodide symporter (MV-NIS)

Hum Gene Ther. 2012 Apr;23(4):419-27. doi: 10.1089/hum.2011.158. Epub 2012 Mar 9.

Abstract

Engineered measles virus (MV) strains deriving from the vaccine lineage represent a promising oncolytic platform and are currently being tested in phase I trials. In this study, we have demonstrated that MV strains genetically engineered to express the human sodium iodide symporter (NIS) have significant antitumor activity against glioma lines and orthotopic xenografts; this compares favorably with the MV strain expressing the human carcinoembryonic antigen, which is currently in clinical testing. Expression of NIS protein in infected cells results in effective concentration of radioactive iodine, which allows for in vivo monitoring of localization of MV-NIS infection by measuring uptake of (123)I or (99m)Tc. In addition, radiovirotherapy with MV-NIS followed by (131)I administration resulted in significant increase of MV-NIS antitumor activity as compared with virus alone in both subcutaneous (p=0.0003) and orthotopic (p=0.004) glioblastoma models. In conclusion, MV-NIS-based radiovirotherapy has significant antitumor activity against glioblastoma multiforme and represents a promising candidate for clinical translation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Glioblastoma / radiotherapy
  • Glioblastoma / therapy*
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Measles virus / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses / genetics*
  • Symporters / genetics*
  • Symporters / metabolism
  • Transplantation, Heterologous

Substances

  • Iodine Radioisotopes
  • Symporters
  • sodium-iodide symporter