title: Effective radiovirotherapy for malignant gliomas by using oncolytic measles virus strains encoding the sodium iodide symporter (MV-NIS).
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.
authors.affiliation: Department of Oncology, Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Opyrchal
authors.forename: Cory
authors.initials: C
authors.lastname: Allen
authors.forename: Ianko
authors.initials: I
authors.lastname: Iankov
authors.forename: Ileana
authors.initials: I
authors.lastname: Aderca
authors.forename: Mark
authors.initials: M
authors.lastname: Schroeder
authors.forename: Jann
authors.initials: J
authors.lastname: Sarkaria
authors.forename: Evanthia
authors.initials: E
authors.lastname: Galanis
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008459:Measles virus / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics*; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters