Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program

Christopher L. Morton, Peter J. Houghton, E. Anders Kolb, Richard Gorlick, C. Patrick Reynolds, Min H. Kang, John M. Maris, Stephen T. Keir, Jianrong Wu, Malcolm A. Smith

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Background. Seneca Valley virus (NTX-010) is a nonrecombinant, replication competent RNA virus that is undergoing phase 1 clinical trials in adults for tumors with neuroendocrine characteristics. Here we have evaluated the antitumor activity of NTX-010 administered systemically. Procedures. In vitro NTX-010 was tested against 23 cell lines exposed for 96 hr at 1 × 10-4 to 104 viral particles (vp)/cell. In vivo NTX-010 was administered intravenously once at 3 × 1012 vp/kg. Three measures of antitumor activity were used: (1) an objective response measure modeled after the clinical setting; (2) a treated to control (T/C) tumor volume measure; and (3) a time to event (fourfold increase in tumor volume for solid tumor models), measure based on the median event-free survival (EFS) of treated and control animals for each xenograft. Results. In vitro NTX-010 demonstrated a marked cytotoxic effect in a subset of the cell lines from the neuroblastoma, Ewingsar coma, and rhabdomyosarcoma panels. In vivo the most consistent activitywas observed for the rhabdomyosarcoma and the neuroblastoma panels, with all four of the alveolar rhabdomyosarcoma xenografts and four of five neuroblastoma xenografts achieving CR or maintained CR. Objective responses were also observed in the rhabdoid tumor,Wilms tumor, and glioblastoma panels. Conclusions. NTX-010 demonstrated a high level of activity both in vitro and in vivo. Further analysis of existingtestingand molecular characterization data may help define the biological characteristics of cancer cells that are associated with response to NTX-010.

Original languageEnglish (US)
Pages (from-to)295-303
Number of pages9
JournalPediatric Blood and Cancer
Volume55
Issue number2
DOIs
StatePublished - Aug 1 2010

Keywords

  • Developmental therapeutics
  • Preclinical testing
  • Seneca Valley virus (NTX-010)

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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    Morton, C. L., Houghton, P. J., Kolb, E. A., Gorlick, R., Reynolds, C. P., Kang, M. H., Maris, J. M., Keir, S. T., Wu, J., & Smith, M. A. (2010). Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program. Pediatric Blood and Cancer, 55(2), 295-303. https://doi.org/10.1002/pbc.22535