Systemic delivery of oncolytic viruses: hopes and hurdles.
Systemic delivery of oncolytic viruses: hopes and hurdles.
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DOI：
10.1155/2012/805629
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发表时间：
2012
影响因子：
2.2
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Ferguson MS;Lemoine NR;Wang Y
尽管最近在手术和放化疗方面取得了进展，但晚期癌症的死亡率仍然很高。迫切需要新的治疗策略;一种选择是全身性溶瘤病毒治疗。静脉给药提供了同时治疗原发性肿瘤和任何转移性沉积物的机会。来自临床试验的数据表明，溶瘤病毒可以安全地全身递送，毒性有限，但结果在疗效方面是不确定的，特别是当与辅助化疗一起递送时。其中一个关键原因是病毒在到达目标之前就从循环中迅速清除。这种现象主要通过中和抗体、补体激活、抗病毒细胞因子和组织驻留巨噬细胞以及其他组织（如肺、肝和脾）的非特异性摄取以及次优病毒从血管隔室逃逸介导。文献中已经报道了一系列方法，这些方法旨在克服临床前模型中的这些障碍。在本文中，潜在的优势，和障碍，成功的溶瘤病毒的全身交付进行了讨论。下一个发展阶段将是开始临床试验，将这些新方法与全身递送的溶瘤病毒相结合，以克服这些障碍。
Despite recent advances in both surgery and chemoradiotherapy, mortality rates for advanced cancer remain high. There is a pressing need for novel therapeutic strategies; one option is systemic oncolytic viral therapy. Intravenous administration affords the opportunity to treat both the primary tumour and any metastatic deposits simultaneously. Data from clinical trials have shown that oncolytic viruses can be systemically delivered safely with limited toxicity but the results are equivocal in terms of efficacy, particularly when delivered with adjuvant chemotherapy. A key reason for this is the rapid clearance of the viruses from the circulation before they reach their targets. This phenomenon is mainly mediated through neutralising antibodies, complement activation, antiviral cytokines, and tissue-resident macrophages, as well as nonspecific uptake by other tissues such as the lung, liver and spleen, and suboptimal viral escape from the vascular compartment. A range of methods have been reported in the literature, which are designed to overcome these hurdles in preclinical models. In this paper, the potential advantages of, and obstacles to, successful systemic delivery of oncolytic viruses are discussed. The next stage of development will be the commencement of clinical trials combining these novel approaches for overcoming the barriers with systemically delivered oncolytic viruses.