Selective tropism of seneca valley virus for variant subtype small cell lung cancer Academic Article uri icon

Overview

MeSH Major

  • Basic Helix-Loop-Helix Transcription Factors
  • Carcinoma, Small Cell
  • Lung Neoplasms
  • Oncolytic Viruses
  • Picornaviridae

abstract

  • We assessed the efficacy of Seneca Valley virus (SVV-001), a neuroendocrine cancer-selective oncolytic picornavirus, in primary heterotransplant mouse models of small cell lung cancer (SCLC), including three lines each of classic and variant SCLC. Half-maximal effective concentrations for cell lines derived from three variant heterotransplants ranged from 1.6×10(-3) (95% confidence interval [CI] = 1×10(-3) to 2.5×10(-3)) to 3.9×10(-3) (95% CI = 2.8×10(-3) to 5.5×10(-3)). Sustained tumor growth inhibition in vivo was only observed in variant lines (two-sided Student t test, P < .005 for each). Doses of 10(14) vp/kg were able to completely and durably eradicate tumors in a variant SCLC heterotransplant model in two of six mice. Gene expression profiling revealed that permissive lines are typified by lower expression of the early neurogenic transcription factor ASCL1 and, conversely, by higher expression of the late neurogenic transcription factor NEUROD1. This classifier demonstrates a sensitivity of .89, specificity of .92, and accuracy of .91. The NEUROD1 to ASCL1 ratio may serve as a predictive biomarker of SVV-001 efficacy.

publication date

  • July 17, 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3888137

Digital Object Identifier (DOI)

  • 10.1093/jnci/djt130

PubMed ID

  • 23739064

Additional Document Info

start page

  • 1059

end page

  • 65

volume

  • 105

number

  • 14