Characterization of the Antiglioma Effect of the Oncolytic Adenovirus VCN-01

PLoS One. 2016 Jan 25;11(1):e0147211. doi: 10.1371/journal.pone.0147211. eCollection 2016.

Abstract

Despite the recent advances in the development of antitumor therapies, the prognosis for patients with malignant gliomas remains dismal. Therapy with tumor-selective viruses is emerging as a treatment option for this devastating disease. In this study we characterize the anti-glioma effect of VCN-01, an improved hyaluronidase-armed pRB-pathway-selective oncolytic adenovirus that has proven safe and effective in the treatment of several solid tumors. VCN-01 displayed a significant cytotoxic effect on glioma cells in vitro. In vivo, in two different orthotopic glioma models, a single intra-tumoral administration of VCN-01 increased overall survival significantly and led to long-term survivors free of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus E1A Proteins / genetics
  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / physiology*
  • Animals
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Cytopathogenic Effect, Viral
  • E2F1 Transcription Factor / genetics
  • Genes, Synthetic
  • Genes, Viral
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • Hyaluronoglucosaminidase / genetics
  • Injections, Intralesional
  • Mice
  • Neoplastic Stem Cells
  • Oligopeptides / genetics
  • Oncolytic Virotherapy*
  • Oncolytic Viruses / genetics
  • Oncolytic Viruses / physiology*
  • Organisms, Genetically Modified
  • Virus Replication
  • Xenograft Model Antitumor Assays

Substances

  • Adenovirus E1A Proteins
  • E1A protein 243R, Human adenovirus type 5
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Oligopeptides
  • arginyl-glycyl-aspartic acid
  • Hyaluronoglucosaminidase

Grants and funding

This work was supported by the European Union (Marie Curie IRG270459 to MMA), the Instituto de Salud Carlos III y los Fondos Feder Europeos (PI13/125 to MMA), the Spanish Ministry of Science and Innovation (Ramón y Cajal contract RYC-2009-05571 to MMA), The L`OREAL-Unesco Foundation (to MMA), The Department of Health of the Government of Navarra (to MMA), The Basque Foundation for Health Research (BIOEF, BIO13/CI/005) and the Caja Navarra Foundation (to MMA). EX is supported by a fellowship from the Credit Andorra Foundation. AAR is supported by a fellowship from Friends of the University of Navarra (ADA). RA is supported by BIO2011-30299-C02-01 from the Spanish Ministry of Education and Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. VCN bioscience provided support in the form of salaries or research support for authors MC and RA, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.