Oncolytic measles virus as a novel therapy for malignant peripheral nerve sheath tumors

Gene. 2015 Jul 1;565(1):140-5. doi: 10.1016/j.gene.2015.04.001. Epub 2015 Apr 2.

Abstract

Malignant peripheral nerve sheath tumors (MPNSTs) are devastating soft tissue sarcomas that can arise sporadically or in association with neurofibromatosis type I, have a poor prognosis, and have limited treatment options. Oncolytic measles virus therapy has been demonstrated to have significant antitumor properties in a number of different cancers, but the oncolytic potential of a MV Edmonston (MVEdm) vaccine strain engineered to express the human sodium iodide symporter (MV-NIS) on MPNST has not previously been evaluated. MPNST cell lines were found to highly express CD46, a cellular receptor required for measles viral entry, on their cell surface. After in vitro MV-NIS infection, MPNST cell lines showed significant cytopathic effect (CPE), while normal Schwann cells were less susceptible to CPE. Virus localization and distribution could be monitored by imaging of I-125 uptake. Local administration of MV-NIS into MPNST-derived tumors resulted in significant regression of tumor and improved survival. These results demonstrate feasibility of oncolytic measles virus therapy for MPNST patients and the possibility of a novel treatment for patients with NF1 tumors.

Keywords: Malignant peripheral nerve sheath tumor; Measles virus; Oncolytic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Genetic Vectors / administration & dosage*
  • Humans
  • In Vitro Techniques
  • Measles virus / genetics*
  • Neoplasm Transplantation
  • Nerve Sheath Neoplasms / therapy*
  • Oncolytic Virotherapy / methods
  • Oncolytic Viruses / genetics
  • Peripheral Nervous System / pathology*
  • Rats, Sprague-Dawley
  • Schwann Cells / metabolism
  • Schwann Cells / pathology
  • Symporters / genetics
  • Symporters / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Symporters
  • sodium-iodide symporter