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Updated: Jul 2, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Oncolytic vaccinia virotherapy of anaplastic thyroid cancer in vivo
Shu-Fu Lin1, Daniel L Price, Chun-Hao Chen
1Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Context:
Anaplastic thyroid carcinoma (ATC) is a fatal disease with a median survival of only 6 months. Novel therapies are needed to improve dismal outcomes.
Objective:
A mutated, replication-competent, vaccinia virus (GLV-1h68) has oncolytic effects on human ATC cell lines in vitro. We assessed the utility of GLV-1h68 in treating anaplastic thyroid cancer in vivo.
Design:
Athymic nude mice with xenograft flank tumors of human ATCs (8505C and DRO90-1) were treated with a single intratumoral injection of GLV-1h68 at low dose (5x10(5) plaque-forming unit), high dose (5x10(6) plaque-forming unit), or PBS. Virus-mediated marker gene expression (luciferase, green fluorescent protein, and beta-galactosidase), viral biodistribution, and flank tumor volumes were measured.
Results:
Luciferase expression was detected 2 d after injection. Continuous viral replication within tumors was reflected by increasing luciferase activity to d 9. At d 10, tumor viral recovery was increased more than 50-fold as compared with the injected dose, and minimal virus was recovered from the lung, liver, brain, heart, spleen, and kidneys. High-dose virus directly injected into normal tissues was undetectable at d 10. The mean volume of control 8505C tumors increased 50.8-fold by d 45, in contrast to 10.5-fold (low dose) and 2.1-fold (high dose; P=0.028) increases for treated tumors. DRO90-1 tumors also showed significant growth inhibition by high-dose virus. No virus-related toxicity was observed throughout the study.
Conclusions:
GLV-1h68 efficiently infects, expresses transgenes within, and inhibits the growth of ATC in vivo. These promising findings support future clinical trials for patients with ATC.
Insights
A mutated vaccinia virus (GLV-1h68) effectively targets and inhibits anaplastic thyroid cancer (ATC) growth in vivo. This oncolytic virus shows promise for treating this fatal disease with no observed toxicity.
Area of Science:
- Oncology
- Virology
- Gene Therapy
Background:
- Anaplastic thyroid carcinoma (ATC) is a highly aggressive cancer with a poor prognosis.
- There is an urgent need for novel therapeutic strategies to improve survival rates in ATC patients.
Purpose of the Study:
- To evaluate the efficacy of a replication-competent vaccinia virus (GLV-1h68) as an oncolytic agent against anaplastic thyroid cancer in vivo.
- To assess the safety and biodistribution of GLV-1h68 in a preclinical model of ATC.
Main Methods:
- Athymic nude mice bearing human ATC xenografts (8505C and DRO90-1) were treated with intratumoral injections of GLV-1h68 (low or high dose) or PBS.
- Viral replication was monitored via marker gene expression (luciferase).
- Tumor volume changes and viral biodistribution were assessed.
Main Results:
- GLV-1h68 demonstrated efficient replication within ATC tumors, with viral loads increasing significantly by day 10 post-injection.
- High-dose GLV-1h68 treatment resulted in significant inhibition of tumor growth in both 8505C and DRO90-1 xenografts compared to controls.
- The virus was primarily localized to tumors, with minimal recovery from major organs, and no virus-related toxicity was observed.
Conclusions:
- GLV-1h68 is an effective oncolytic virus for inhibiting ATC growth in vivo.
- The virus efficiently infects ATC cells and expresses transgenes within tumors.
- These preclinical findings support the potential of GLV-1h68 for clinical application in anaplastic thyroid cancer treatment.
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