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.
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.
Division of Endocrinology, Department of Medicine, Mayo Clinic and Foundation, Rochester, MN, USA.
H V
HV
Reddi
P
P
Madde
S J
SJ
McDonough
M A
MA
Trujillo
J C
JC
Morris
R M
RM
Myers
K W
KW
Peng
S J
SJ
Russell
B
B
McIver
N L
NL
Eberhardt
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007455:Iodine / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000627:therapeutic use; D008459:Measles virus / Q000235:genetics / Q000378:metabolism*; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy*; D015899:Tomography, Emission-Computed, Single-Photon; D014709:Vero Cells; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
D007455:Iodine; D007457:Iodine Radioisotopes; D051916:Membrane Cofactor Protein; D011991:Receptors, Virus; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C497857:CD46 protein, human