Genetically engineered oncolytic Newcastle disease virus effectively induces sustained remission of malignant pleural mesothelioma.
Genetically engineered oncolytic Newcastle disease virus effectively induces sustained remission of malignant pleural mesothelioma.
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DOI：
10.1158/1535-7163.mct-10-0090
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发表时间：
2010-10
影响因子：
5.7
通讯作者：
Fong Y
中科院分区：
文献类型：
--
作者：
Silberhumer GR;Brader P;Wong J;Serganova IS;Gönen M;Gonzalez SJ;Blasberg R;Zamarin D;Fong Y
恶性胸膜间皮瘤(MPM)是一种高度侵袭性的肿瘤。另一种治疗策略，如溶瘤病毒疗法，可能在未来提供有希望的治疗选择。本研究利用生物发光肿瘤成像技术检测了新城疫基因工程病毒(NDV(F3aa)-GFP)在MPM中的溶瘤效果和诱导肿瘤缓解的作用。体外实验检测了新城疫病毒(F3aa)-GFP对几种间皮瘤细胞株的杀伤作用。转导萤火虫荧光素酶基因MSTO-211H*的胸膜间皮瘤原位移植瘤动物在移植瘤后不同时间点(第1天和第10天)分别给予单剂或多剂新城疫病毒(F3aa)-GFP治疗。通过生物发光成像评估肿瘤负荷。间皮瘤细胞系对新城疫病毒裂解的敏感性呈剂量依赖性，敏感性顺序如下：MSTO-211H>；MSTO-211H*>；H-2452>；VAMT>；JMN.对MSTO-211H*细胞的体内研究显示，在治疗开始后的14天内，65%的动物对病毒治疗完全有效。所有这些动物的长期存活时间均为肿瘤植入后50天(对照组为23天)。多次治疗有效率明显高于单一治疗(p=0.005)。在原位胸膜间皮瘤模型中，新城疫病毒似乎是一种有效的病毒溶瘤剂治疗MPM。
Malignant pleural mesothelioma (MPM) is a highly aggressive tumor. Alternative treatment strategies such as oncolytic viral therapy may offer promising treatment options in the future. In this study, the oncolytic efficacy and induction of tumor remission by a genetically-engineered Newcastle disease virus (NDV(F3aa)-GFP) in MPM is tested and monitored by bioluminescent tumor imaging. The efficacy of NDV(F3aa)-GFP was tested against several mesothelioma cell lines in vitro. Firefly luciferase transduced MSTO-211H* orthotopic pleural mesothelioma tumor-bearing animals were treated with either single or multiple doses of NDV(F3aa)-GFP at different time points (days 1 and 10) after tumor implantation. Tumor burden was assessed by bioluminescence imaging. Mesothelioma cell lines exhibited dose-dependent susceptibility to NDV lysis in the following order of sensitivity: MSTO-211H>MSTO-211H*>H-2452>VAMT>JMN. In vivo studies with MSTO-211H* cells showed complete response to viral therapy in 65% of the animals within 14 days after treatment initiation. Long term survival in all of these animals was > 50 days after tumor installation (control animals <23 days). Multiple compared with single treatment showed a significantly better response (p=0.005). NDV appears to be an efficient viral oncolytic agent in therapy of MPM in an orthotopic pleural mesothelioma tumor model.