title: Treatment of medulloblastoma with a modified measles virus.
abstract: Although treatment of medulloblastoma has improved, at least 30% of patients with this tumor die of progressive disease. Unfortunately, many of the children who survive suffer long-term treatment-related morbidity. Previous studies have demonstrated the efficacy of using oncolytic viruses to eradicate brain tumors. The objective of this study was to test the efficacy of measles virus in treating medulloblastoma. To determine whether medulloblastoma cells are susceptible, 5 different human medulloblastoma cell lines were analyzed for the expression of the measles virus receptor CD46. Fluorescence-activated cell-sorting analysis confirmed expression of CD46 on all cell lines tested, with UW288-1 having the most prominent expression and D283med displaying the lowest expression. CD46 expression was also demonstrated, using immunohistochemistry, in 13 of 13 medulloblastoma tissue specimens. All 5 medulloblastoma cell lines were examined for their susceptibility to measles virus killing in vitro. A measles virus containing the green fluorescent protein (GFP) gene as a marker for infection (MV-GFP) was used. All cell lines exhibited significant killing when infected with MV-GFP, all formed syncytia with infection, all showed fluorescence, and all allowed viral replicaton after infection. In an intracerebral murine xenograft model, a statistically significant increase in survival was seen in animals treated with the active measles virus compared with those treated with inactivated virus. These data demonstrate that medulloblastoma is susceptible to measles virus killing and that the virus may have a role in treating this tumor in the clinical setting.
authors.affiliation: The Center for Childhood Cancer, The Research Institute at Nationwide Children’s Hospital, Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Studebaker
authors.forename: Cole R
authors.initials: CR
authors.lastname: Kreofsky
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Pierson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.forename: Evanthia
authors.initials: E
authors.lastname: Galanis
authors.forename: Corey
authors.initials: C
authors.lastname: Raffel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002469:Cell Separation; D002528:Cerebellar Neoplasms / Q000628:therapy* / Q000821:virology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008459:Measles virus; D008527:Medulloblastoma / Q000628:therapy* / Q000821:virology; D051916:Membrane Cofactor Protein / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D051916:Membrane Cofactor Protein