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Published on: January 7, 2019
The control of anaplastic thyroid carcinoma cell lines by oncolytic poxviruses
Neil Mundi1, Sung Um1, John Yoo2
1Department of Otolaryngology Head & Neck Surgery, Western University, London, ON, Canada.
Background And Significance:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Vaccinia virus shows significant potential as an oncolytic therapy for anaplastic thyroid cancer (ATC). This study found vaccinia virus effectively controlled ATC cell proliferation and induced cell death in vitro.
Area of Science:
- Oncology
- Virology
Background:
- Anaplastic thyroid cancer (ATC) is an aggressive and often fatal malignancy.
- Oncolytic viral therapy presents a promising treatment strategy for ATC.
Purpose of the Study:
- To evaluate the efficacy of poxviruses as oncolytic agents against anaplastic thyroid cancer cell lines.
- To identify the most potent poxvirus for potential ATC treatment.
Main Methods:
- Seven ATC cell lines were infected with modified myxoma, vaccinia, and tanapox viruses expressing GFP.
- Viral proliferation, cell growth (Presto Blue assay, live-dead assay), and progeny production were assessed.
- Vaccinia virus susceptibility was further evaluated in five additional ATC cell lines.
Main Results:
- ATC cell lines exhibited differential susceptibility to the tested poxviruses.
- Vaccinia virus demonstrated superior oncolytic activity compared to myxoma and tanapox viruses.
- Higher titers of vaccinia virus effectively controlled proliferation and induced cell death across various ATC cell lines.
Conclusions:
- Vaccinia virus emerged as the most potent poxvirus for controlling ATC cell proliferation and inducing cell death in vitro.
- These findings suggest vaccinia virus holds promise for improving outcomes in anaplastic thyroid cancer patients.
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