Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia virus carrying the human sodium iodide symporter Journal Article
| Authors: | Gholami, S.; Haddad, D.; Chen, C. H.; Chen, N. G.; Zhang, Q.; Zanzonico, P. B.; Szalay, A. A.; Fong, Y. |
| Article Title: | Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia virus carrying the human sodium iodide symporter |
| Abstract: | Background: Anaplastic thyroid carcinoma (ATC) is fatal with resistance to radiotherapy because of the loss of intrinsic human sodium iodine symporter (hNIS). We determined whether vaccinia virus carrying hNIS kills and induces hNIS reexpression in ATC cells, facilitating deep-tissue imaging. Methods: Vaccinia virus (GLV-1h153) carrying hNIS was tested against ATC lines for killing and replication via cytotoxicity and viral plaque assays. Cellular radiouptake was determined using radiouptake assays. GLV-1h153-infected ATC xenografts were imaged via 99mTc-pertechnetate. Results: GLV-1h153 infected, replicated in, and killed all ATC cell lines. GFP expression confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1.0, GLV-1h153 reached near 100% cytotoxicity in 8305c and FRO by day 5 and 70% in the least sensitive cell line, 8505c. GLV-1h153-infected ATC cells had a 14-fold increase of hNIS-specific radiouptake compared with uninfected control 24 hours after infection at an MOI of 1.0. In vivo, GLV-1h153 facilitated imaging of hNIS expression in 8505c tumors using 99mTc-pertechnetate. Conclusion: GLV-1h153 is an effective oncolytic agent against ATC. The results show hNIS-specific radiouptake in infected ATC cells, facilitating deep-tissue imaging. GLV-1h153 is a promising candidate for treatment and imaging, and potentially enhancing susceptibility to radioiodine therapy by converting non-hNIS-expressing cells into hNIS-expressing ATC cells. © 2011 Published by Mosby, Inc. |
| Keywords: | controlled study; protein expression; human cell; nonhuman; radiopharmaceuticals; animal cell; mouse; animals; mice; cell death; glial fibrillary acidic protein; animal experiment; animal model; cytotoxicity; tumor xenograft; molecular imaging; cell line, tumor; transfection; oncolytic virotherapy; vaccinia virus; thyroid carcinoma; thyroid neoplasms; virus infection; virus replication; carcinoma cell; virus vector; virus titration; sodium iodide symporter; pertechnetic acid tc 99m; symporters; sodium pertechnetate tc 99m; virus plaque |
| Journal Title: | Surgery |
| Volume: | 150 |
| Issue: | 6 |
| ISSN: | 0039-6060 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2011-12-01 |
| Start Page: | 1040 |
| End Page: | 1047 |
| Language: | English |
| DOI: | 10.1016/j.surg.2011.09.010 |
| PROVIDER: | scopus |
| PUBMED: | 22136819 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 January 2012" - "CODEN: SURGA" - "Source: Scopus" |
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