Effects of preexisting immunity on the response to herpes simplex-based oncolytic viral therapy
Effects of preexisting immunity on the response to herpes simplex-based oncolytic viral therapy
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DOI：
10.1089/10430340050207957
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发表时间：
2000-12-01
影响因子：
4.2
通讯作者：
Fong, Y
中科院分区：
文献类型：
--
作者：
Delman, KA;Bennett, JJ;Fong, Y
1型单纯疱疹病毒（HSV）是许多抗癌策略的基础，这些策略在动物模型中被证明是有效的。它们是天然的人类病原体，大多数成年人具有抗hsv免疫力。目前的研究在小鼠模型中研究了预先存在的免疫对基于疱疹的溶瘤病毒治疗肝转移癌的反应的影响，该模型旨在模拟可能用于非神经系统肿瘤的临床方法。具体来说，研究人员在免疫正常的小鼠中检测了两种多突变的HSV-1溶瘤病毒NV1020或G207的抗癌作用，这些小鼠先前接种过野生型1型单纯疱疹病毒。小鼠对HSV-1具有体液和细胞介导的免疫。在测试的剂量下，肿瘤对溶瘤治疗的反应并没有被对HSV的免疫所明显地消除。在局部肝动脉和静脉给药模型中也检测了病毒给药途径的影响。病毒给药途径影响疗效，因为静脉注射病毒会产生一些可检测到的衰减，而肝动脉治疗则不受影响。这些结果表明，当给予适当剂量并合理接近肿瘤靶点时，基于单纯疱疹病毒的溶瘤治疗仍然可以预期是肝脏恶性肿瘤患者的有效治疗。
Herpes simplex viruses (HSV) type 1 are the basis of a number of anticancer strategies that have proven efficacious in animal models. They are natural human pathogens and the majority of adults have anti-HSV immunity. The current study examined the effect of preexisting immunity on the response to herpes-based oncolytic viral treatment of hepatic metastatic cancer in a murine model designed to simulate a clinical approach likely to be utilized for nonneurological tumors. Specifically, the anticancer effects of NV1020 or G207, two multimutated HSV-1 oncolytic viruses, were tested in immunocompetent mice previously immunized with a wild-type herpes simplex type 1 virus. Mice were documented to have humoral as well as cell-mediated immunity to HSV-1. Tumor response to oncolytic therapy was not measurably abrogated by immunity to HSV at the doses tested. The influence of route of viral administration was also tested in models of regional hepatic arterial and intravenous therapy. Route of viral administration influenced efficacy, as virus delivered intravenously produced some detectable attenuation while hepatic arterial therapy remained unaffected. These results demonstrate that when given at appropriate doses and in reasonable proximity to tumor targets, HSV-based oncolytic therapy can still be expected to be effective treatment for patients with hepatic malignancies.