Context: Anaplastic thyroid carcinoma 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 anaplastic thyroid carcinoma 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 anaplastic thyroid carcinomas (8505C and DRO90–1) were treated with a single intratumoral injection of GLV-1h68 at low dose (5x10⁵ pfu), high dose (5x10⁶ pfu), or PBS. Virus-mediated marker gene expression (luciferase, GFP and -galactosidase), viral biodistribution, and flank tumor volumes were measured.

Results: Luciferase expression was detected 2 days after injection. Continuous viral replication within tumors was reflected by increasing luciferase activity to day 9. At day 10, tumor viral recovery was increased >50-fold as compared to 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 day 10. The mean volume of control 8505C tumors increased 50.8-fold by day 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 anaplastic thyroid carcinoma in vivo. These promising findings support future clinical trials for patients with anaplastic thyroid carcinoma.