Oncolytic measles virus strains have significant antitumor activity against glioma stem cells

C. Allen, M. Opyrchal, I. Aderca, M. A. Schroeder, Jann N Sarkaria, E. Domingo, Mark J Federspiel, Evanthia Galanis

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Glioblastoma (GBM) is the most common primary brain tumor in adults and has a dismal prognosis despite multimodality treatment. Given the resistance of glioma stem cells (GSC) to chemotherapy and radiation therapy, their eradication could prevent tumor recurrence. We sought to evaluate the antitumor activity of measles virus (MV) derivatives against GSC. We generated neurosphere cultures from patient-derived primary tumor GBM xenografts, and we characterized them for the GSC markers CD133, SOX2, Nestin, ATF5 and OLIG2. Using the MV-strains MV-GFP, MV-CEA and MV-NIS we demonstrated infection, viral replication and significant cytopathic effect in vitro against GSC lines. In tumorigenicity experiments, GBM44 GSC were infected with MV in vitro and subsequently implanted into the right caudate nucleus of nude mice: significant prolongation of survival in mice implanted with infected GSC was observed, compared with mock-infected controls (P=0.0483). In therapy experiments in GBM6 and GBM12 GSC xenograft models, there was significant prolongation of survival in MV-GFP-treated animals compared with inactivated virus-treated controls (GBM6 P=0.0021, GBM12 P=0.0416). Abundant syncytia and viral replication was demonstrated in tumors of MV-treated mice. Measles virus derivatives have significant antitumor activity against glioma-derived stem cells in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)444-449
Number of pages6
JournalGene Therapy
Volume20
Issue number4
DOIs
StatePublished - Apr 2013

Fingerprint

Oncolytic Viruses
Measles virus
Glioma
Stem Cells
Glioblastoma
Heterografts
Nestin
Oncogenic Viruses
Survival
Caudate Nucleus
Virus Diseases
Giant Cells
Nude Mice
Brain Neoplasms
Neoplasms
Radiotherapy
Viruses

Keywords

  • gliomas
  • measles virus
  • MV-CEA
  • MV-NIS
  • stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Oncolytic measles virus strains have significant antitumor activity against glioma stem cells. / Allen, C.; Opyrchal, M.; Aderca, I.; Schroeder, M. A.; Sarkaria, Jann N; Domingo, E.; Federspiel, Mark J; Galanis, Evanthia.

In: Gene Therapy, Vol. 20, No. 4, 04.2013, p. 444-449.

Research output: Contribution to journalArticle

Allen, C. ; Opyrchal, M. ; Aderca, I. ; Schroeder, M. A. ; Sarkaria, Jann N ; Domingo, E. ; Federspiel, Mark J ; Galanis, Evanthia. / Oncolytic measles virus strains have significant antitumor activity against glioma stem cells. In: Gene Therapy. 2013 ; Vol. 20, No. 4. pp. 444-449.
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