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

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.—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. Vaccinia virus GLV‐1h153 in combination with 131 I shows increased efficiency in treating triple‐negative breast cancer. FASEB J. 28, 676–682 (2014). www.fasebj.org