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Oncolytic Vaccinia Virotherapy of Anaplastic Thyroid Cancer in Vivo

Departments of Surgery (S.-F.L., D.L.P., C.-H.C., S.L., L.G., Y.F., R.J.W.) and Radiology (P.B.), Memorial Sloan-Kettering Cancer Center, New York, New York 10021; Department of Internal Medicine (S.-F.L., C.-H.C.), Chang Gung Memorial Hospital, Taoyuan, 33305 Taiwan, Republic of China; Genelux Corporation (Q.Z., Y.A.Y., N.C., A.A.S.), San Diego Science Center, San Diego, California 92109; and Rudolf-Virchow Center for Experimental Biomedicine and Biocenter (A.A.S.), Institute of Microbiology and Biochemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany

Address all correspondence and requests for reprints to: Richard J. Wong, M.D., Head and Neck Service, C-1069, Memorial Sloan-Kettering Cancer Center, New York, New York 10021. E-mail: wongr{at}mskcc.org.

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 x 10⁵ plaque-forming unit), high dose (5 x 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.

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