title: Oncolytic measles virus as a novel therapy for malignant peripheral nerve sheath tumors.
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.
authors.affiliation: Department of Medical Genetics, Mayo Clinic, Rochester, MN 55905, USA; Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: deyle.david@mayo.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Deyle
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Diana Zarate
authors.initials: DZ
authors.lastname: Escobar
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Kah-Whye
authors.initials: KW
authors.lastname: Peng
authors.affiliation: Department of Medical Genetics, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: dbabovic@mayo.edu.
authors.forename: Dusica
authors.initials: D
authors.lastname: Babovic-Vuksanovic
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D008459:Measles virus / Q000235:genetics*; D009368:Neoplasm Transplantation; D018317:Nerve Sheath Neoplasms / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics; D017933:Peripheral Nervous System / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
chemical_list: D027981:Symporters; D000099209:Sodium-Iodide Symporters
keywords: Malignant peripheral nerve sheath tumor; Measles virus; Oncolytic therapy