Selective tropism of seneca valley virus for variant subtype small cell lung cancer

J. T. Poirier, Irina Dobromilskaya, Whei F. Moriarty, Craig D. Peacock, Christine L. Hann, Charles M. Rudin

Research output: Contribution to journalArticle

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 1014 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.

Original languageEnglish (US)
Pages (from-to)1059-1065
Number of pages7
JournalJournal of the National Cancer Institute
Volume105
Issue number14
DOIs
StatePublished - Jul 17 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Poirier, J. T., Dobromilskaya, I., Moriarty, W. F., Peacock, C. D., Hann, C. L., & Rudin, C. M. (2013). Selective tropism of seneca valley virus for variant subtype small cell lung cancer. Journal of the National Cancer Institute, 105(14), 1059-1065. https://doi.org/10.1093/jnci/djt130