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首页> 外文期刊>Journal of orthopaedic research >Oncolytic vesicular stomatitis virus administered by isolated limb perfusion suppresses osteosarcoma growth.
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Oncolytic vesicular stomatitis virus administered by isolated limb perfusion suppresses osteosarcoma growth.

机译：通过单独的肢体灌注施用溶瘤性水疱性口炎病毒可抑制骨肉瘤的生长。

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摘要

A significant limitation to oncolytic virotherapy in vivo is the lack of a clinically relevant means of delivering the virus. We evaluated the oncolytic activity of vesicular stomatitis virus (VSV) in human osteosarcoma cells and explored isolated limb perfusion (ILP) as a novel oncolytic virus delivery system to extremity sarcoma in immune-competent rats. Human and rat osteosarcoma cells transduced with rVSV-lacZ uniformly expressed beta-gal. VSV was fully capable of replicating its RNA genome in all osteosarcoma cell lines, and efficiently killed them in time- and dose-dependent manners, whereas normal bone marrow stromal cells were refractory to the virus. VSV delivered by ILP inhibited growth of osteosarcoma xenografts more potently than that injected intravenously and intratumorally in the hind limb of immune-competent rats. Histopathological sections of tumor lesions treated by ILP-delivered VSV showed positive for VSV-G protein. There were no VSV-G expressions in perfused leg muscle, nonperfused leg muscle, brain, lung, and liver in VSV-treated rats. Our findings show efficient VSV gene expression and replication in osteosarcoma cells, suggesting that osteosarcoma may be a promising target for oncolytic virotherapy with VSV. Furthermore, we firstly showed that ILP of VSV against extremity sarcoma caused antitumor activity.
机译：体内溶瘤病毒疗法的显着局限性是缺乏临床上相关的病毒传递手段。我们评估了人骨肉瘤细胞中水泡性口炎病毒（VSV）的溶瘤活性，并探讨了孤立肢体灌注（ILP）作为一种新的溶瘤病毒传递系统，以免疫能力强的大鼠肢体肉瘤。用rVSV-lacZ转导的人和大鼠骨肉瘤细胞均表达β-gal。 VSV完全能够在所有骨肉瘤细胞系中复制其RNA基因组，并以时间和剂量依赖性方式有效杀死它们，而正常的骨髓基质细胞对该病毒具有抵抗力。由ILP递送的VSV比具有免疫能力的大鼠后肢的静脉和瘤内注射对骨肉瘤异种移植物的生长抑制作用更强。经ILP递送的VSV治疗的肿瘤病变的组织病理学切片显示VSV-G蛋白阳性。在VSV治疗的大鼠中，在灌注的腿部肌肉，未灌注的腿部肌肉，脑，肺和肝脏中没有VSV-G表达。我们的发现显示骨肉瘤细胞中有效的VSV基因表达和复制，表明骨肉瘤可能是VSV溶瘤病毒疗法的有希望的靶标。此外，我们首先表明，VSV对肢体肉瘤的ILP引起抗肿瘤活性。

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