The control of anaplastic thyroid carcinoma cell lines by oncolytic poxviruses
2014
Mundi, Neil | Um, Sung | Yoo, John | Rizzo, Giananthony | Black, Morgan | Pinto, Nicole | Palma, David A. | Fung, Kevin | MacNeil, Danielle | Mymryk, Joe S. | Barrett, John W. | Nichols, Anthony C.
Anaplastic thyroid cancer (ATC) is rare, but its clinical presentation is often dramatic and aggressive and is nearly uniformly fatal. Oncolytic viral therapy is a potential strategy to improve outcomes for patients suffering with this disease.Seven established ATC cell lines were infected with a panel of poxviruses to identify which virus had the most potential as an oncolytic agent. These included myxoma, vaccinia, and tanapox viruses, all modified to express green fluorescence protein (GFP). Viral proliferation was assessed by fluorescence and viral amplification. The effect on cell line growth was assessed by the Presto Blue metabolic assay and a live-dead assay. A replication assay was performed to assess the production of infectious progeny. An additional five ATC cell lines were tested using the assays described above for susceptibility to vaccinia virus.ATC cell lines were differentially susceptible to each virus. Vaccinia virus was superior to myxoma and tanapox viruses for the control of anaplastic thyroid cancer in vitro. Although subsequent investigation using an expanded panel of cell lines revealed differential susceptibility to vaccinia virus, effective control of cell proliferation was still achieved using higher titers.Vaccinia virus was the most potent of the tested poxviruses and was highly effective in controlling proliferation and inducing cell death in ATC cell lines. The efficacy of these viruses offers hope for improving outcomes for patients suffering with ATC.
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