Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the IFN response and HMGB1
Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the IFN response and HMGB1
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DOI：
10.1038/gt.2010.121
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发表时间：
2011-02-01
期刊：
影响因子：
5.1
通讯作者：
Thorne, S. H.
中科院分区：
文献类型：
--
作者：
Huang, B.;Sikorski, R.;Thorne, S. H.
溶瘤病毒或肿瘤选择性病毒领域的最新进展意味着这些药物的临床应用正在被更详细地考虑。与大多数癌症疗法一样，它们可能主要与其他疗法联合使用。尽管一些报道已经表明溶瘤病毒可以在受感染的癌细胞内与化疗协同作用，但确定从受感染细胞释放的因子是否可以在远处增强化疗的作用将是特别重要的。在这里，我们证明了体外溶瘤牛痘和紫杉烷之间的协同作用。然而，我们也首次表明，这种协同作用至少部分是由于感染细胞释放的因子能够使周围细胞对化疗敏感。几种细胞因子被确定为这种旁观者效应的介质，包括感染后不久释放的I型干扰素和细胞死亡后释放的高迁移率族蛋白B1（HMGB 1）。这代表了病毒和传统肿瘤治疗之间有益相互作用的这些机制的首次描述。这些数据可以为目前临床上使用的药物的临床试验设计提供直接基础，并为下一代病毒载体的开发提供见解。Gene Therapy（2011）18，164-172; doi：10.1038/gt.2010.121; 2010年8月26日在线发表
Recent developments in the field of oncolytic or tumor-selective viruses have meant that the clinical applications of these agents are now being considered in more detail. Like most cancer therapies it is likely that they will be used primarily in combination with other therapeutics. Although several reports have shown that oncolytic viruses can synergize with chemotherapies within an infected cancer cell, it would be particularly important to determine whether factors released from infected cells could enhance the action of chemotherapies at a distance. Here, we demonstrate in vitro synergy between oncolytic vaccinia and taxanes. However, we also show, for the first time, that this synergy is at least partly due to the release of factors from the infected cells that are capable of sensitizing surrounding cells to chemotherapy. Several cellular factors were identified as being mediators of this bystander effect, including type I interferon released soon after infection and high-mobility group protein B1 (HMGB1) released after cell death. This represents the first description of these mechanisms for beneficial interactions between viral and traditional tumor therapies. These data may provide a direct basis for the design of clinical trials with agents currently in the clinic, as well as providing insight into the development of next generation viral vectors. Gene Therapy (2011) 18, 164-172; doi:10.1038/gt.2010.121; published online 26 August 2010