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Published on: August 23, 2019
Treatment of anaplastic thyroid carcinoma in vitro with a mutant vaccinia virus
Shu-Fu Lin1, Zhenkun Yu, Christopher Riedl
1Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Background:
Anaplastic thyroid carcinoma (ATC) is a fatal disease resistant to all conventional treatments. Novel therapies are needed to improve dismal outcomes.
Methods:
A replication-competent vaccinia virus (GLV-1h68) was engineered by inserting expression cassettes encoding Renilla luciferase-green fluorescent protein (GFP), beta-galactosidase, and beta-glucuronidase into the genome of LIVP strain. Infection of 6 ATC cell lines by GLV-1h68 was detected in vitro at 12, 24, and 36 hours. Viral proliferation was measured through viral plaque assays. Cytotoxicity was measured daily at a multiplicity of infection (MOI) of 0.01, 0.1 and 1.
Results:
Viral infection was detected in all cell lines by 24 hours and increased in intensity at 36 hours. Logarithmic viral replication was detected in all cell lines. At MOI 1, <13% cell survival was measured in 5 cell lines by day 7. At MOI 0.01, 3 cell lines showed <21% cell survival by day 7. Luciferase and beta-galactosidase activity at 24 hours correlated with cytotoxicity at MOI 0.01 on day 5.
Conclusion:
A replication-competent vaccinia virus has significant infectious and oncolytic activity against a panel of human ATC. These results encourage future in vivo and clinical studies for this novel agent to treat this fatal cancer.
Insights
A novel vaccinia virus shows promise in treating anaplastic thyroid carcinoma (ATC), a deadly cancer resistant to traditional therapies. This engineered virus demonstrated significant oncolytic activity in laboratory studies, paving the way for future clinical trials.
Area of Science:
- Oncolytic virotherapy
- Cancer research
- Viral gene therapy
Background:
- Anaplastic thyroid carcinoma (ATC) is an aggressive and fatal cancer with limited treatment options.
- Conventional therapies are largely ineffective against ATC, highlighting the urgent need for novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of a replication-competent vaccinia virus (GLV-1h68) as a potential treatment for anaplastic thyroid carcinoma.
- To assess the virus's infectious and oncolytic activity against human ATC cell lines in vitro.
Main Methods:
- Engineered a replication-competent vaccinia virus (GLV-1h68) with reporter genes (Renilla luciferase, GFP, beta-galactosidase, beta-glucuronidase).
- Infected six human ATC cell lines and monitored viral infection, proliferation (plaque assays), and cytotoxicity at various multiplicities of infection (MOI).
Main Results:
- GLV-1h68 demonstrated significant viral replication and infection in all tested ATC cell lines.
- High oncolytic activity was observed, with cell survival below 13% in most cell lines by day 7 at MOI 1.
- Reporter gene activity correlated with observed cytotoxicity, supporting the virus's oncolytic potential.
Conclusions:
- The engineered vaccinia virus (GLV-1h68) exhibits substantial infectious and oncolytic activity against human anaplastic thyroid carcinoma cells.
- These findings support further investigation of this oncolytic virus in preclinical and clinical settings for ATC treatment.
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