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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MSK Authors
  1. Shu - Fu Lin
    9 Lin
  2. Peter Brader
    25 Brader
  3. Daniel Louis Price
    6 Price
  4. Richard J Wong
    416 Wong
  5. Yuman Fong
    775 Fong
  6. Chun-Hao Chen
    42 Chen
  7. Sen Li
    19 Li