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

doi:10.1093/jnci/djt130

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

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 language	English (US)
Pages (from-to)	1059-1065
Number of pages	7
Journal	Journal of the National Cancer Institute
Volume	105
Issue number	14
DOIs	https://doi.org/10.1093/jnci/djt130
State	Published - Jul 17 2013

ASJC Scopus subject areas

Oncology
Cancer Research

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title = "Selective tropism of seneca valley virus for variant subtype small cell lung cancer",

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.",

author = "Poirier, {J. T.} and Irina Dobromilskaya and Moriarty, {Whei F.} and Peacock, {Craig D.} and Hann, {Christine L.} and Rudin, {Charles M.}",

note = "Funding Information: American Association of Clinical Research/ Caring for Carcinoid Foundation (grant 109884); Flight Attendant Medical Research Institute Center of Excellence in Translational Research; Burroughs Wellcome Fund Clinical Scientist Award in Translational Research (all to CMR). The funders had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication.",

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AU - Poirier, J. T.

AU - Dobromilskaya, Irina

AU - Moriarty, Whei F.

AU - Peacock, Craig D.

AU - Hann, Christine L.

AU - Rudin, Charles M.

N1 - Funding Information: American Association of Clinical Research/ Caring for Carcinoid Foundation (grant 109884); Flight Attendant Medical Research Institute Center of Excellence in Translational Research; Burroughs Wellcome Fund Clinical Scientist Award in Translational Research (all to CMR). The funders had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication.

PY - 2013/7/17

Y1 - 2013/7/17

N2 - 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.

AB - 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.

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

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