Vaccinia virus GLV-1h153 in combination with 131I shows increased efficiency in treating triple-negative breast cancer

Sepideh Gholami, Chun Hao Chen, Emil Lou, Laurence J. Belin, Sho Fujisawa, Valerie A. Longo, Nanhai G. Chen, Mithat Gönen, Pat B. Zanzonico, Aladar A. Szalay, Yuman Fong

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

We investigated the therapeutic efficacy of a replication-competent oncolytic vaccinia virus, GLV-1h153, carrying human sodium iodide symporter (hNIS), in combination with radioiodine in an orthotopic triple-negative breast cancer (TNBC) murine model. In vitro viral infection was confirmed by immunoblotting and radioiodine uptake assays. Orthotopic xenografts (MDA-MB-231 cells) received intratumoral injection of GLV-1h153 or PBS. One week after viral injection, xenografts were randomized into 4 treatment groups: GLV-1h153 alone, GLV-1h153 and 131I (∼5 mCi), 131I alone, or PBS, and followed for tumor growth. Kruskal-Wallis and Wilcoxon tests were performed for statistical analysis. Radiouptake assay showed a 178-fold increase of radioiodine uptake in hNIS-expressing infected cells compared with PBS control. Systemic 131I-iodide in combination with GLV-1h153 resulted in a 6-fold increase in tumor regression (24 compared to 146 mm3 for the virus-only treatment group; P<0.05; d 40). We demonstrated that a novel vaccinia virus, GLV-1h153, expresses hNIS, increases the expression of the symporter in TNBC cells, and serves both as a gene marker for noninvasive imaging of virus and as a vehicle for targeted radionuclide therapy with 131I.

Original languageEnglish (US)
Pages (from-to)676-682
Number of pages7
JournalFASEB Journal
Volume28
Issue number2
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Keywords

  • Radiation therapy
  • Symporter

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Gholami, S., Chen, C. H., Lou, E., Belin, L. J., Fujisawa, S., Longo, V. A., Chen, N. G., Gönen, M., Zanzonico, P. B., Szalay, A. A., & Fong, Y. (2014). Vaccinia virus GLV-1h153 in combination with 131I shows increased efficiency in treating triple-negative breast cancer. FASEB Journal, 28(2), 676-682. https://doi.org/10.1096/fj.13-237222