Species D human adenovirus type 9 exhibits better virus-spread ability for antitumor efficacy among alternative serotypes.
Species D human adenovirus type 9 exhibits better virus-spread ability for antitumor efficacy among alternative serotypes.
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DOI：
10.1371/journal.pone.0087342
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ugai H
中科院分区：
文献类型：
--
作者：
Uchino J;Curiel DT;Ugai H
C种人腺病毒血清型5（HAdV-C5）被广泛用作癌症基因治疗的载体，因为它有效地转导靶细胞。已经开发了多种HAdV-C5载体，并在体外和体内进行了癌症基因治疗的测试。虽然使用HAdV-C5载体的临床试验在许多癌症患者中产生了有效的应答，但将HAdV-C5载体施用至实体瘤在有限的区域中显示出应答。肿瘤块中的生物屏障被认为阻碍HAdV-C5载体从感染细胞的病毒传播。因此，成功的癌症基因治疗需要有效的病毒从受感染的肿瘤细胞扩散到周围的肿瘤细胞。在这项研究中，我们比较了HAdV-C5的16个其他HAdV血清型从物种A到G的病毒传播能力在体外。HAdV-D9具有较强的病毒传播能力，其子代病毒在病毒复制过程中能有效地从感染细胞中释放出来。尽管HAdV-D9纤维蛋白含有科萨基B病毒和腺病毒受体（CAR）的结合位点，但由于人CAR（hCAR）-非依赖性附着于靶细胞，HAdV-D9显示出扩大的感染向性。HAdV-D9感染有效地杀死hCAR阴性癌细胞以及hCAR阳性癌细胞。这些结果表明，与HAdV-C5相比，HADV-D9具有更好的病毒传播能力，可以改善实体瘤的治疗效果。
Species C human adenovirus serotype 5 (HAdV-C5) is widely used as a vector for cancer gene therapy, because it efficiently transduces target cells. A variety of HAdV-C5 vectors have been developed and tested in vitro and in vivo for cancer gene therapy. While clinical trials with HAdV-C5 vectors resulted in effective responses in many cancer patients, administration of HAdV-C5 vectors to solid tumors showed responses in a limited area. A biological barrier in tumor mass is considered to hinder viral spread of HAdV-C5 vectors from infected cells. Therefore, efficient virus-spread from an infected tumor cell to surrounding tumor cells is required for successful cancer gene therapy. In this study, we compared HAdV-C5 to sixteen other HAdV serotypes selected from species A to G for virus-spread ability in vitro. HAdV-D9 showed better virus-spread ability than other serotypes, and its viral progeny were efficiently released from infected cells during viral replication. Although the HAdV-D9 fiber protein contains a binding site for coxsackie B virus and adenovirus receptor (CAR), HAdV-D9 showed expanded tropism for infection due to human CAR (hCAR)-independent attachment to target cells. HAdV-D9 infection effectively killed hCAR-negative cancer cells as well as hCAR-positive cancer cells. These results suggest that HADV-D9, with its better virus-spread ability, could have improved therapeutic efficacy in solid tumors compared to HAdV-C5.
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影响因子：
82.9
作者：
Gaggar, A;Shayakhmetov, DM;Lieber, A
通讯作者：
Lieber, A
影响因子：
--
作者：
Beatty, Matthew S.;Curiel, David T.
通讯作者：
Curiel, David T.
影响因子：
5.4
作者：
Arnberg, N;Kidd, AH;Wadell, G
通讯作者：
Wadell, G
影响因子：
4.1
作者：
Asaoka, K;Tada, M;Abe, H
通讯作者：
Abe, H
影响因子：
3.7
作者：
Blusch, JH;Deryckere, F;Burgert, HG
通讯作者：
Burgert, HG