Oncolytic vaccinia therapy of squamous cell carcinoma.
Oncolytic vaccinia therapy of squamous cell carcinoma.
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DOI：
10.1186/1476-4598-8-45
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发表时间：
2009-07-06
期刊：
影响因子：
37.3
通讯作者：
Wong RJ
中科院分区：
文献类型：
--
作者：
Yu Z;Li S;Brader P;Chen N;Yu YA;Zhang Q;Szalay AA;Fong Y;Wong RJ
新的治疗方法是必要的，以改善与鳞状细胞癌（SCC）的头部和颈部的患者的结果。历史上，牛痘病毒作为疫苗被广泛用于人类，并导致天花的根除。我们研究了减毒的，可复制的牛痘病毒（GLV-1h 68）作为一种溶瘤剂对一组六个人头颈部SCC细胞系的治疗效果。早在病毒暴露后6小时，所有6种细胞系均支持病毒转基因表达（β-半乳糖苷酶、绿色荧光蛋白和荧光素酶）。在四种细胞系中观察到有效的转基因表达和病毒复制（在72小时内滴度增加>150倍）。在感染复数（MOI）为1时，GLV-1h 68对4种细胞系具有高度细胞毒性，6天内细胞毒性≥ 90%，其余2种细胞系的细胞毒性>45%。即使在0.01的非常低的MOI下，三种细胞系在6天内仍表现出>60%的细胞死亡。单次瘤内注射GLV-1h 68（5 × 106 pfu）至小鼠MSKQLL 2异种移植物中，显示局部瘤内荧光素酶活性在第2-4天达到峰值，在10天内逐渐消退，无扩散至正常器官的证据。治疗动物在24天内表现出几乎完全的肿瘤消退，没有观察到任何毒性，而对照动物则表现出快速的肿瘤进展。这些结果证明了减毒牛痘病毒在体外和体内感染和裂解头颈部SCC的显著溶瘤功效，并支持其在未来临床试验中的继续研究。
Novel therapies are necessary to improve outcomes for patients with squamous cell carcinomas (SCC) of the head and neck. Historically, vaccinia virus was administered widely to humans as a vaccine and led to the eradication of smallpox. We examined the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68) as an oncolytic agent against a panel of six human head and neck SCC cell lines. All six cell lines supported viral transgene expression (β-galactosidase, green fluorescent protein, and luciferase) as early as 6 hours after viral exposure. Efficient transgene expression and viral replication (>150-fold titer increase over 72 hrs) were observed in four of the cell lines. At a multiplicity of infection (MOI) of 1, GLV-1h68 was highly cytotoxic to the four cell lines, resulting in ≥ 90% cytotoxicity over 6 days, and the remaining two cell lines exhibited >45% cytotoxicity. Even at a very low MOI of 0.01, three cell lines still demonstrated >60% cell death over 6 days. A single injection of GLV-1h68 (5 × 106 pfu) intratumorally into MSKQLL2 xenografts in mice exhibited localized intratumoral luciferase activity peaking at days 2–4, with gradual resolution over 10 days and no evidence of spread to normal organs. Treated animals exhibited near-complete tumor regression over a 24-day period without any observed toxicity, while control animals demonstrated rapid tumor progression. These results demonstrate significant oncolytic efficacy by an attenuated vaccinia virus for infecting and lysing head and neck SCC both in vitro and in vivo, and support its continued investigation in future clinical trials.
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影响因子：
3.8
作者：
Lin, Shu-Fu;Yu, Zhenkun;Wong, Richard J.
通讯作者：
Wong, Richard J.
影响因子：
46.9
作者：
Yu, YA;Shabahang, S;Szalay, AA
通讯作者：
Szalay, AA
影响因子：
11.2
作者：
Zhang, Qian;Yu, Yong A.;Szalay, Aladar A.
通讯作者：
Szalay, Aladar A.
影响因子：
5.8
作者：
Lin, Shu-Fu;Price, Daniel L.;Wong, Richard J.
通讯作者：
Wong, Richard J.
影响因子：
5.4
作者：
Yang, G;Pevear, DC;Jordan, R
通讯作者：
Jordan, R