Transduction of Liver Metastases After Intravenous Injection of Ad5/35 or Ad35 Vectors With and Without Factor X-Binding Protein Pretreatment
Transduction of Liver Metastases After Intravenous Injection of Ad5/35 or Ad35 Vectors With and Without Factor X-Binding Protein Pretreatment
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DOI：
10.1089/hum.2008.142
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发表时间：
2009-06-01
影响因子：
4.2
通讯作者：
Lieber, Andre
中科院分区：
文献类型：
--
作者：
Liu, Ying;Wang, Hongjie;Lieber, Andre
用靶向腺病毒载体进行的低效肿瘤转导主要是由于血液成分（包括凝血因子X）和枯否细胞清除的非特异性病毒隔离。在这项研究中，我们表明，预先注射蛇毒因子X-结合蛋白（X-bp）减少肝细胞转导，并增加血液中的静脉注射，纤维嵌合Ad 5/35载体的循环时间。X-bp预处理改善了Ad 5/35对肝转移瘤的转导，并提高了基于Ad 5/35的溶瘤腺病毒的抗肿瘤功效。此外，我们证明了基于腺病毒血清型35的载体，其被X因子较少隔离，在肿瘤靶向中是有效的。这给出了在癌症的病毒疗法中使用基于Ad 35的载体的基本原理。
Inefficient tumor transduction with targeted adenoviral vectors is largely due to unspecific virus sequestration by blood components, including coagulation factor X, and Kupffer cell scavenging. In this study, we show that preinjection of snake venom factor X-binding protein (X-bp) reduces hepatocyte transduction and increases the circulation time in blood of an intravenously injected, fiber-chimeric Ad5/35 vector. X-bp pretreatment resulted in improved Ad5/35 transduction of liver metastases and increased the antitumor efficacy of an Ad5/35-based oncolytic adenovirus. Furthermore, we demonstrate that a vector based on adenoviral serotype 35, which is less sequestered by factor X, is efficient in tumor targeting. This gives a rationale for using Ad35-based vectors in virotherapy of cancer.