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西多福韦对端粒酶特异性复制选择性溶瘤腺病毒OBP-301(Telomelysin)的抗病毒活性。

Antiviral activity of cidofovir against telomerase-specific replication-selective oncolytic adenovirus, OBP-301 (Telomelysin).

作者信息

Ouchi Masaaki, Kawamura Hitoshi, Urata Yasuo, Fujiwara Toshiyoshi

机构信息

Oncolys BioPharma, Inc., Tokyo, 106-0032, Japan.

出版信息

Invest New Drugs. 2009 Jun;27(3):241-5. doi: 10.1007/s10637-008-9169-5. Epub 2008 Aug 27.

Abstract

We constructed a replication-competent oncolytic adenovirus, OBP-301 (Telomelysin), in which human telomerase reverse transcriptase (hTERT) promoter drives E1 genes. OBP-301 is currently being used in a phase-I clinical trial for various types of tumors. Under such conditions, anti-adenoviral agents should be available for safety use against OBP-301 since any adenoviral viremia could cause severe adverse effects. Cidofovir (CDV) is an acyclic nucleoside phosphonate that has a broad antiviral activity against DNA viruses. Here, we examined the antiviral effects of CDV against OBP-301. The in vitro cytopathic effects of OBP-301 were suppressed by CDV. Moreover, CDV decreased the adenoviral E1A gene copy number after OBP-301 infection. These results suggest that CDV is a potentially useful antiviral agent for OBP-301.

摘要

我们构建了一种具有复制能力的溶瘤腺病毒OBP-301(端粒溶素),其中人端粒酶逆转录酶(hTERT)启动子驱动E1基因。OBP-301目前正在用于各类肿瘤的I期临床试验。在这种情况下,由于任何腺病毒血症都可能导致严重不良反应,因此应备有抗腺病毒药物以便安全用于对抗OBP-301。西多福韦(CDV)是一种无环核苷膦酸盐,对DNA病毒具有广泛的抗病毒活性。在此,我们研究了CDV对OBP-301的抗病毒作用。CDV抑制了OBP-301的体外细胞病变效应。此外,CDV在OBP-301感染后降低了腺病毒E1A基因拷贝数。这些结果表明,CDV是一种对OBP-301可能有用的抗病毒药物。

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