Intravenous injection of oncolytic picornavirus SVV-001 prolongs animal survival in a panel of primary tumor-based orthotopic xenograft mouse models of pediatric glioma

Neuro Oncol. 2013 Sep;15(9):1173-85. doi: 10.1093/neuonc/not065. Epub 2013 May 7.


Background: Seneca Valley virus (SVV-001) is a nonpathogenic oncolytic virus that can be systemically administered and can pass through the blood-brain barrier. We examined its therapeutic efficacy and the mechanism of tumor cell infection in pediatric malignant gliomas.

Methods: In vitro antitumor activities were examined in primary cultures, preformed neurospheres, and self-renewing glioma cells derived from 6 patient tumor orthotopic xenograft mouse models (1 anaplastic astrocytoma and 5 GBM). In vivo therapeutic efficacy was examined by systemic treatment of preformed xenografts in 3 permissive and 2 resistant models. The functional role of sialic acid in mediating SVV-001 infection was investigated using neuraminidase and lectins that cleave or competitively bind to linkage-specific sialic acids.

Results: SVV-001 at a multiplicity of infection of 0.5 to 25 replicated in and effectively killed primary cultures, preformed neurospheres, and self-renewing stemlike single glioma cells derived from 4 of the 6 glioma models in vitro. A single i.v. injection of SVV-001 (5 × 10(12) viral particles/kg) led to the infection of orthotopic xenografts without harming normal mouse brain cells, resulting in significantly prolonged survival in all 3 permissive and 1 resistant mouse models (P < .05). Treatment with neuraminidase and competitive binding using lectins specific for α2,3-linked and/or α2,6-linked sialic acid significantly suppressed SVV-001 infectivity (P < .01).

Conclusion: SVV-001 possesses strong antitumor activity against pediatric malignant gliomas and utilizes α2,3-linked and α2,6-linked sialic acids as mediators of tumor cell infection. Our findings support the consideration of SVV-001 for clinical trials in children with malignant glioma.

Keywords: SVV-001; malignant glioma; oncolytic virus; orthotopic xenograft; sialic acid.

MeSH terms

  • Animals
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / therapy*
  • Disease Models, Animal
  • Glioma / metabolism
  • Glioma / therapy*
  • Injections, Intravenous
  • Mice
  • Mice, SCID
  • N-Acetylneuraminic Acid / metabolism
  • Oncolytic Virotherapy*
  • Oncolytic Viruses*
  • Picornaviridae*
  • Survival Analysis
  • Xenograft Model Antitumor Assays


  • N-Acetylneuraminic Acid