Oncolytic vaccinia virotherapy of anaplastic thyroid cancer in vivo Journal Article
| Authors: | Lin, S. F.; Price, D. L.; Chen, C. H.; Brader, P.; Li, S.; Gonzalez, L.; Zhang, Q.; Yu, Y. A.; Chen, N.; Szalay, A. A.; Fong, Y.; Wong, R. J. |
| Article Title: | Oncolytic vaccinia virotherapy of anaplastic thyroid cancer in vivo |
| Abstract: | 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 × 10 5 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 virusrelated 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. Copyright © 2008 by The Endocrine Society. |
| Keywords: | controlled study; unclassified drug; human cell; nonhuman; antineoplastic agent; mouse; animals; mice; cell division; gene expression; tumor volume; green fluorescent protein; luciferase; in vivo study; cancer cell culture; cell line, tumor; mus musculus; cancer inhibition; cancer vaccines; mice, nude; carcinoma; beta galactosidase; vaccinia virus; transplantation, heterologous; single drug dose; thyroid cancer; thyroid neoplasms; glv 1h68; virus replication; neoplasm transplantation; viral vaccines; anaplastic carcinoma; genetic markers; virotherapy; giardia lamblia virus; plaque assay |
| Journal Title: | Journal of Clinical Endocrinology and Metabolism |
| Volume: | 93 |
| Issue: | 11 |
| ISSN: | 0021-972X |
| Publisher: | Oxford University Press |
| Date Published: | 2008-11-01 |
| Start Page: | 4403 |
| End Page: | 4407 |
| Language: | English |
| DOI: | 10.1210/jc.2008-0316 |
| PUBMED: | 18697871 |
| PROVIDER: | scopus |
| PMCID: | PMC3728375 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 15" - "Export Date: 17 November 2011" - "CODEN: JCEMA" - "Source: Scopus" |
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