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Neuro Oncol. 2015 Dec;17(12):1568-77. doi: 10.1093/neuonc/nov058. Epub 2015 Apr 2.

Oncolytic measles virus efficacy in murine xenograft models of atypical teratoid rhabdoid tumors.

Author information

1
Center for Childhood Cancer and Blood Diseases, Research Institute at Nationwide Children's Hospital, Columbus, Ohio (A.W.S., B.H.); Nationwide Children's Hospital Department of Pathology and Laboratory Medicine and Departments of Pathology and Anatomy, The Ohio State University College of Medicine, Columbus, Ohio (C.R.P.); Animal Resources Core, Research Institute at Nationwide Children's Hospital, Columbus, Ohio (T.A.S.); Department of Neurological Surgery and Pediatrics, University of California, San Francisco, California (C.R.); Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland (E.M.J.).

Abstract

BACKGROUND:

Atypical teratoid rhabdoid tumor (AT/RT) is a rare, highly malignant pediatric tumor of the central nervous system that is usually refractory to available treatments. The aggressive growth, propensity to disseminate along the neuroaxis, and young age at diagnosis contribute to the poor prognosis. Previous studies have demonstrated the efficacy of using oncolytic measles virus (MV) against localized and disseminated models of medulloblastoma. The purpose of this study was to evaluate the oncolytic potential of MV in experimental models of AT/RT.

METHODS:

Following confirmation of susceptibility to MV infection and killing of AT/RT cells in vitro, nude mice were injected with BT-12 and BT-16 AT/RT cells stereotactically into the caudate nucleus (primary tumor model) or lateral ventricle (disseminated tumor model). Recombinant MV was administered either intratumorally or intravenously. Survival was determined for treated and control animals. Necropsy was performed on animals showing signs of progressive disease.

RESULTS:

All cell lines exhibited significant killing when infected with MV, all formed syncytia with infection, and all generated infectious virus after infection. Orthotopic xenografts displayed cells with rhabdoid-like cellular morphology, were negative for INI1 expression, and showed dissemination within the intracranial and spinal subarachnoid spaces. Intratumoral injection of live MV significantly prolonged the survival of animals with intracranial and metastatic tumors.

CONCLUSION:

These data demonstrate that AT/RT is susceptible to MV killing and suggest that the virus may have a role in treating this tumor in the clinical setting.

KEYWORDS:

atypical teratoid rhabdoid tumor; intravenous; measles virus; oncolytic virus

PMID:
25838138
PMCID:
PMC4633925
DOI:
10.1093/neuonc/nov058
[Indexed for MEDLINE]
Free PMC Article

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