Eradication of advanced hepatocellular carcinoma in rats via repeated hepatic arterial infusions of recombinant VSV.
Eradication of advanced hepatocellular carcinoma in rats via repeated hepatic arterial infusions of recombinant VSV.
复制标题
通过反复肝动脉输注重组 VSV 根除大鼠晚期肝细胞癌。
DOI：
10.1002/hep.20536
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Woo,SavioLC
中科院分区：
文献类型：
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作者：
Shinozaki,Katsunori;Ebert,Oliver;Woo,SavioLC
在癌细胞中选择性复制的病毒作为治疗恶性肿瘤的新型治疗剂具有相当大的前景。水泡性口炎病毒(VSV)是一种非致病性的RNA病毒，由于许多肿瘤的抗病毒反应减弱，具有固有的溶瘤特异性。我们报道，在携带晚期多灶性肝细胞癌(HCC)的大鼠中，重复肝动脉注射重组合胞体形成VSV载体，载体剂量减少10倍，可导致持续的肿瘤选择性病毒复制，直到血液中出现高滴度中和抗体。没有注意到血清转氨酶和肝脏病理的显著升高，表明没有肝脏毒性。随着完全坏死的肿瘤结节被单核吞噬细胞包围，病变的纤维化和钙化，血管生成和正常肝实质的再生，肿瘤反应得到显著改善。经10倍载体单次注射后，荷瘤大鼠的存活率显著提高(P=.001)，且前者有18%的动物获得了长期无瘤生存，后者为0%。结论：VSV介导的病毒治疗作为一种治疗晚期肝癌的新型治疗手段，在未来的发展中将是非常有用的。(HEPATOLOGY 2005；41：196-203。)
Viruses that replicate selectively in cancer cells hold considerable promise as novel therapeutic agents for the treatment of malignancy. Vesicular stomatitis virus (VSV) is a nonpathogenic RNA virus with intrinsic oncolytic specificity due to attenuated antiviral responses in many tumors. We report that repeated hepatic arterial infusion of recombinant syncytia‐forming VSV vector in advanced multifocal hepatocellular carcinoma (HCC)‐bearing rats at a 10‐fold reduced vector dose resulted in sustained tumor‐selective virus replication until the onset of high‐titer neutralizing antibodies in blood. No significant elevations in serum transaminases and liver pathology were noted, indicating a lack of hepatotoxicity. Substantially improved tumor response was achieved with completely necrotic tumor nodules surrounded by mononuclear phagocytic cells, followed by fibrosis and calcification of the lesions, angiogenesis, and regeneration of normal hepatic parenchyma. Survival of tumor‐bearing rats treated with repeated vector infusions was not only significantly improved over that of animals after a single injection at 10 times the vector dose (P= .001), but 18% of animals in the former treatment group also achieved long‐term and tumor‐free survival compared with 0% of animals in the latter treatment group.In conclusion, this treatment regimen will be very useful in the future development of VSV‐mediated virotherapy as a novel therapeutic modality for patients with advanced HCC. (HEPATOLOGY2005;41:196–203.)