An adenoviral vector expressing human adenovirus 5 and 3 fiber proteins for targeting heterogeneous cell populations

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• 作者：Miho Murakami ; Hideyo Ugai ; Minghui Wang ; Natalya Belousova ; Paul Dent ; Paul B. Fisher ; Joel N. Glasgow ; Maaike Everts ; David T. Curiel
• 关键词：Adenovirus ; Mosaic ; Fiber ; Tumor ; Tropism expansion
• 刊名：Virology
• 出版年：2010
• 出版时间：25 November 2010
• 年：2010
• 卷：407
• 期：2
• 页码：196-205
• 全文大小：1437 K

文摘

Human adenovirus serotype 5 (HAdV-5) attaches to its primary receptor, the coxsackie and adenovirus receptor (CAR) as the first step of infection. However, CAR expression decreases as tumors progress, thereby diminishing the utility of HAdV-5-based vectors for cancer therapy. In contrast, many aggressive tumor cells highly express CD46, a cellular receptor for HAdV-3. We hypothesized that a mosaic HAdV vector, containing two kinds of fiber proteins, would provide extensive transduction in a heterogeneous population of tumor cells with varying expression levels of HAdV receptors. We therefore generated a fiber-mosaic HAdV vector displaying both a chimeric HAdV-3 fiber and the HAdV-5 fiber protein. We verified the structural integrity of purified viral particles and confirmed that the fiber-mosaic HAdV vector has expanded tropism. We conclude that the use of fiber-mosaic HAdV vectors is a promising approach for transducing a heterogeneous cell population with different expression levels of adenovirus receptors.