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Preclinical efficacy of the oncolytic measles virus expressing the sodium iodide symporter in iodine non-avid anaplastic thyroid cancer: a novel therapeutic agent allowing noninvasive imaging and radioiodine therapy

Cancer Gene Therapy volume 19, pages 659–665 (2012)Cite this article

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Abstract

Anaplastic thyroid cancer is an extremely aggressive disease resistant to radioiodine treatment because of loss of sodium iodide symporter (NIS) expression. To enhance prognosis of this fatal cancer, we validated the preclinical efficacy of measles virus (MV)-NIS, the vaccine strain of the oncolytic MV (MV-Edm), modified to include the NIS gene. Western blotting analysis confirmed that a panel of eight anaplastic thyroid cancer (ATC)-derived cell lines do not express NIS protein, but do express CD46, the MV receptor. In vitro cell death assays and in vivo xenograft studies demonstrate the oncolytic efficacy of MV-NIS in BHT-101 and KTC-3, ATC-derived cell lines. Radioactive iodine uptake along with single-photon emission computed tomography (SPECT)-computed tomography imaging of KTC-3 xenografts after 99Tcm administration confirmed NIS expression in vitro and in vivo, respectively, after virus treatment. Adjuvant administration of RAI, to MV-NIS-treated KTC-3 tumors showed a trend for increased tumor cell killing. As current treatment for ATC is only palliative, and MV-NIS is currently Food and Drug Administration approved for human clinical trials in myeloma, our data indicate that targeting ATC with MV-NIS could prove to be a novel therapeutic strategy for effective treatment of iodine-resistant ATC and will expedite its testing in clinical trials for this aggressive disease.

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Acknowledgements

This work was supported by a research grant from the Wendy Will Case Cancer Fund (HVR) and Fraternal Order of Eagles (HVR) and Mayo Foundation (NLE). We thank our nuclear medicine technologist, Tracy Decklever for technical expertise and imaging assistance. We thank Dr Mark J Federspiel and the staff of the Viral Vector Production Laboratory for supplying clinical grade MV-NIS.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Mayo Clinic and Foundation, Rochester, MN, USA,

    H V Reddi, P Madde, S J McDonough, M A Trujillo, J C Morris III, B McIver & N L Eberhardt

  2. Department of Molecular Medicine, Mayo Clinic and Foundation, Rochester, MN, USA

    R M Myers, K W Peng, S J Russell & B McIver

  3. Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, MN, USA

    N L Eberhardt

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  1. H V Reddi
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Correspondence to N L Eberhardt.

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Competing interests

Drs SJR and KWP are named inventors on patents employing viral vectors for therapeutic purposes. Drs SJR and JCM, III are named inventors on a patent employing NIS expression for noninvasive monitoring of gene delivery.

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Supplementary Information accompanies this paper on the Cancer Gene Therapy website

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Reddi, H., Madde, P., McDonough, S. et al. Preclinical efficacy of the oncolytic measles virus expressing the sodium iodide symporter in iodine non-avid anaplastic thyroid cancer: a novel therapeutic agent allowing noninvasive imaging and radioiodine therapy. Cancer Gene Ther 19, 659–665 (2012). https://doi.org/10.1038/cgt.2012.47

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