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 2012 Sep;19(9):659-65
Date
07/14/2012Pubmed ID
22790962DOI
10.1038/cgt.2012.47Scopus ID
2-s2.0-84865266991 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
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 (99)Tc(m) 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.
Author List
Reddi HV, Madde P, McDonough SJ, Trujillo MA, Morris JC 3rd, Myers RM, Peng KW, Russell SJ, McIver B, Eberhardt NLMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Western
Cell Line, Tumor
Female
Genetic Therapy
Humans
Iodine
Iodine Radioisotopes
Measles virus
Membrane Cofactor Protein
Mice
Mice, Nude
Oncolytic Virotherapy
Oncolytic Viruses
Receptors, Virus
Symporters
Thyroid Carcinoma, Anaplastic
Thyroid Neoplasms
Tomography, Emission-Computed, Single-Photon
Vero Cells
Xenograft Model Antitumor Assays