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

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 (131)I (∼ 5 mCi), (131)I 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 (131)I-iodide in combination with GLV-1h153 resulted in a 6-fold increase in tumor regression (24 compared to 146 mm(3) 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 (131)I.

• Authors: 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
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 28 Issue 2 Pg. 676-82 (Feb 2014) ISSN: 1530-6860 [Electronic] United States
• PMID: 24186964 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Iodine Radioisotopes

Topics

• Animals
• Blotting, Western
• Cell Line, Tumor
• Female
• Fluorescent Antibody Technique
• Humans
• Immunoblotting
• Iodine Radioisotopes (therapeutic use)
• Mice
• Triple Negative Breast Neoplasms (metabolism, radiotherapy, therapy)
• Vaccinia virus (genetics, physiology)