Oncolytic Vaccinia Virotherapy of Anaplastic Thyroid Cancer in Vivo
Oncolytic Vaccinia Virotherapy of Anaplastic Thyroid Cancer in Vivo
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DOI：
10.1210/jc.2008-0316
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发表时间：
2008-11-01
影响因子：
5.8
通讯作者：
Wong, Richard J.
中科院分区：
文献类型：
--
作者：
Lin, Shu-Fu;Price, Daniel L.;Wong, Richard J.
背景：甲状腺未分化癌（ATC）是一种致死性疾病，中位生存期仅为6个月。目的：研究一种具有复制能力的变异型痘苗病毒（GLV-1h 68）对人ATC细胞株的体外溶瘤作用。设计：用低剂量（5 × 10（5）空斑形成单位）、高剂量（5 × 10（6）空斑形成单位）或PBS单次瘤内注射GLV-1h 68治疗具有人ATC（8505 C和DRO 90 -1）异种移植侧腹肿瘤的无胸腺裸鼠。病毒介导的标记基因表达（荧光素酶，绿色荧光蛋白，β-半乳糖苷酶），病毒的生物分布，和侧翼肿瘤体积进行了measured.Results：荧光素酶的表达检测后2天注射。肿瘤内连续的病毒复制通过增加荧光素酶活性至第9天来反映。在第10天，与注射剂量相比，肿瘤病毒回收率增加了50倍以上，并且从肺、肝、脑、心脏、脾和肾中回收了最少的病毒。高剂量病毒直接注射到正常组织中在第10天检测不到。到第45天，对照8505 C肿瘤的平均体积增加了50.8倍，而治疗肿瘤的平均体积增加了10.5倍（低剂量）和2.1倍（高剂量; P = 0.028）。DRO 90 -1肿瘤也显示出高剂量病毒的显著生长抑制。在整个study.Conclusions：GLV-1h 68有效地感染，表达转基因内，并抑制ATC在体内的生长。这些有希望的发现支持未来ATC患者的临床试验。（临床内分泌代谢杂志93：4403-4407，2008）
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 10(5) plaque-forming unit), high dose (5 x 10(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. (J Clin Endocrinol Metab 93: 4403-4407, 2008)