Fusogenic vesicular stomatitis virus for the treatment of head and neck squamous carcinomas

Otolaryngol Head Neck Surg. 2007 May;136(5):811-7. doi: 10.1016/j.otohns.2006.11.046.

Abstract

Objectives: This study investigates the efficacy of recombinant fusogenic VSV [rVSV-NDV/F(L289A) or rVSV-F] in the treatment of head and neck squamous cell carcinoma (HNSCC).

Study design and setting: The in vitro replication and cytotoxicity of rVSV-F were studied in two human SCC cell lines, in one murine SCC cell line, and in human keratinocytes. The effects on tumor size and animal survival were investigated following in vivo rVSV-F treatment of floor-of-mouth tumor model C3H/HeJ mice.

Results: Recombinant VSV-F preferentially induced rapid syncytia formation, and replicated in (P < 0.04) and killed (P < 1 x 10(-13)) all three SCC lines tested. The virus had no observable effect on human keratinocytes. Tumor size was smaller (P < 0.03) and overall survival was better (P < 0.001) for treated animals than for control animals.

Conclusion/significance: Recombinant VSV-F confers a modest survival benefit for HNSCC in this orthotopic murine model. This oncolytic virus holds promise as a novel cancer treatment for recurrent HNSCC.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / therapy*
  • Carcinoma, Squamous Cell / virology*
  • Cell Line, Tumor
  • Cell Survival
  • DNA Primers / genetics
  • Giant Cells / virology
  • Head and Neck Neoplasms / therapy*
  • Head and Neck Neoplasms / virology*
  • Humans
  • In Vitro Techniques
  • Keratinocytes / virology
  • Mice
  • Phenotype
  • Polymerase Chain Reaction
  • Recombinant Fusion Proteins / genetics*
  • Rhabdoviridae Infections / genetics
  • Rhabdoviridae Infections / virology*
  • Vesicular stomatitis Indiana virus / genetics*
  • Virus Replication / genetics

Substances

  • DNA Primers
  • Recombinant Fusion Proteins