文章：

溶瘤细胞的病毒

Oncolytic viruses

原文发布日期：2002-12-01

DOI: 10.1038/nrc948

类型: Review Article

开放获取: 否

要点：

1. Viruses can be engineered to selectively infect and/or replicate in cancer cells.
2. Selective infection uses redirection of viral binding away from normal and towards normal cells.
3. Selective replication can be targeted towards cells with overactive RAS or defective interferon signalling, cells with defects in the p16/RB tumour-suppressor pathway, or cells with defects in the p53 tumour-suppressor pathway. Additional means of targeted replication use tumour-selective promoters to drive expression of viral genes.
4. Clinical trials have shown that oncolytic viruses — that are derived from adenoviruses such as herpes simplex virus and Newcastle disease virus — are well tolerated in humans.
5. The main goals of oncolytic viral research are to increase tumour selectivity by modifying the viral genome, to combine oncolytic viral therapy with standard radiation and chemotherapy, and to 'arm' the viruses with suicide cDNAs and/or cytokine cDNAs for multimodal treatment.
6. Improving our understanding of the mechanisms of viral oncolysis and the immune responses that virues induce, as well as improving the ability to image these viruses in vivo, should make this therapeutic approach safer and more effective.

要点翻译：

1. 病毒可以被改造以选择性感染和/或在癌细胞中复制。
2. 选择性感染通过改变病毒结合特性，使其避开正常细胞而靶向癌细胞实现。
3. 选择性复制可针对具有过度活跃RAS或干扰素信号传导缺陷的细胞、p16/RB肿瘤抑制通路缺陷的细胞，或p53肿瘤抑制通路缺陷的细胞。其他靶向复制方式利用肿瘤选择性启动子驱动病毒基因表达。  
4. 临床试验表明，源于腺病毒（如单纯疱疹病毒和新城疫病毒）的溶瘤病毒在人体中具有良好的耐受性。
5. 溶瘤病毒研究的主要目标包括：通过修饰病毒基因组增强肿瘤选择性，将溶瘤病毒疗法与标准放疗和化疗相结合，以及为病毒装备自杀cDNA和/或细胞因子cDNA以实现多模式治疗。  
6. 提高对病毒溶瘤机制及病毒诱导免疫反应的理解，同时增强体内病毒成像能力，将使这种治疗方法更安全、更有效。

英文摘要：

Although the cytotoxic effects of viruses are usually viewed in terms of pathogenicity, it is possible to harness this activity for therapeutic purposes. Viral genomes are highly versatile, and can be modified to direct their cytotoxicity towards cancer cells. These viruses are known as oncolytic viruses. How are viruses engineered to become tumour specific, and can they be used to safely treat cancer in humans?

摘要翻译： 

尽管病毒的细胞毒性效应通常被视为致病性，但也可将其用于治疗目的。病毒基因组具有高度可塑性，可被改造以使其细胞毒性靶向癌细胞。这类病毒被称为溶瘤病毒。如何对病毒进行工程改造使其具备肿瘤特异性？它们能否安全用于人类癌症治疗？

原文链接：

Oncolytic viruses