title: Intravenous injection of oncolytic picornavirus SVV-001 prolongs animal survival in a panel of primary tumor-based orthotopic xenograft mouse models of pediatric glioma.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors: Diana Helis Henry Medical Research Foundation, New Orleans, LA, USA.
authors: Zhigang
authors: Z
authors: Liu
authors: Xiumei
authors: X
authors: Zhao
authors: Hua
authors: H
authors: Mao
authors: Patricia A
authors: PA
authors: Baxter
authors: Yulun
authors: Y
authors: Huang
authors: Litian
authors: L
authors: Yu
authors: Lalita
authors: L
authors: Wadhwa
authors: Jack M
authors: JM
authors: Su
authors: Adekunle
authors: A
authors: Adesina
authors: Lazlo
authors: L
authors: Perlaky
authors: Mary
authors: M
authors: Hurwitz
authors: Neeraja
authors: N
authors: Idamakanti
authors: Seshidhar Reddy
authors: SR
authors: Police
authors: Paul L
authors: PL
authors: Hallenbeck
authors: Richard L
authors: RL
authors: Hurwitz
authors: Ching C
authors: CC
authors: Lau
authors: Murali
authors: M
authors: Chintagumpala
authors: Susan M
authors: SM
authors: Blaney
authors: Xiao-Nan
authors: XN
authors: Li
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D005910:Glioma / Q000378:metabolism / Q000628:therapy*; D007275:Injections, Intravenous; D051379:Mice; D016513:Mice, SCID; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses; D010849:Picornaviridae; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D019158:N-Acetylneuraminic Acid
keywords: SVV-001; malignant glioma; oncolytic virus; orthotopic xenograft; sialic acid
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