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Shu-Fu Lin, Daniel L. Price, Chun-Hao Chen, Peter Brader, Sen Li, Lorena Gonzalez, Qian Zhang, Yong A. Yu, Nanhai Chen, Aladar A. Szalay, Yuman Fong, Richard J. Wong, Oncolytic Vaccinia Virotherapy of Anaplastic Thyroid Cancer in Vivo, The Journal of Clinical Endocrinology & Metabolism, Volume 93, Issue 11, 1 November 2008, Pages 4403–4407, https://doi.org/10.1210/jc.2008-0316
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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 (5 × 105 plaque-forming unit), high dose (5 × 106 plaque-forming unit), or PBS. Virus-mediated marker gene expression (luciferase, green fluorescent protein, and β-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.
