Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Lin, SF; Price, DL; Chen, CH; Brader, P; Li, S; Gonzalez, L; Zhang, Q; Yu, YA; Chen, N; Szalay, AA; Fong, Y; Wong, RJ.
Oncolytic vaccinia virotherapy of anaplastic thyroid cancer in vivo.
J Clin Endocrinol Metab. 2008; 93(11):4403-4407
Doi: 10.1210/jc.2008-0316
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- Co-Autor*innen der Med Uni Graz
- Brader Peter
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- 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 (5x10(5) plaque-forming unit), high dose (5x10(6) plaque-forming unit), or PBS. Virus-mediated marker gene expression (luciferase, green fluorescent protein, and beta-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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cancer Vaccines - therapeutic use
- Carcinoma - immunology
- Cell Division - drug effects
- Cell Line, Tumor -
- Genetic Markers -
- Humans -
- Mice -
- Mice, Nude -
- Neoplasm Transplantation -
- Plaque Assay -
- Thyroid Neoplasms - immunology
- Transplantation, Heterologous -
- Vaccinia virus - immunology
- Viral Vaccines - therapeutic use