人腺病毒血清型5、6、11和35作为抗癌剂的特性研究。
Characterization of human adenovirus serotypes 5, 6, 11, and 35 as anticancer agents.
作者信息
Shashkova Elena V, May Shannon M, Barry Michael A
机构信息
Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55902, USA.
出版信息
Virology. 2009 Nov 25;394(2):311-20. doi: 10.1016/j.virol.2009.08.038. Epub 2009 Sep 18.
Human adenovirus type 5 (Ad5) has been the most popular platform for the development of oncolytic Ads. Alternative Ad serotypes with low seroprevalence might allow for improved anticancer efficacy in Ad5-immune patients. We studied the safety and efficacy of rare serotypes Ad6, Ad11 and Ad35. In vitro cytotoxicity of the Ads correlated with expression of CAR and CD46 in most but not all cell lines. Among CAR-binding viruses, Ad5 was often more active than Ad6, among CD46-binding viruses Ad35 was generally more cytotoxic than Ad11 in cell culture studies. Ad5, Ad6, and Ad11 demonstrated similar anticancer activity in vivo, whereas Ad35 was not efficacious. Hepatotoxicity developed only in Ad5-injected mice. Predosing with Ad11 and Ad35 did not increase infection of hepatocytes with Ad5-based vector demonstrating different interaction of these Ads with Kupffer cells. Data obtained in this study suggest developing Ad6 and Ad11 as alternative Ads for anticancer treatment.
5型人腺病毒（Ad5）一直是溶瘤腺病毒开发中最常用的载体。血清流行率较低的其他腺病毒血清型可能会提高对Ad5免疫患者的抗癌疗效。我们研究了罕见血清型Ad6、Ad11和Ad35的安全性和疗效。在大多数但并非所有细胞系中，腺病毒的体外细胞毒性与柯萨奇病毒和腺病毒受体（CAR）及CD46的表达相关。在与CAR结合的病毒中，在细胞培养研究中，Ad5通常比Ad6更具活性；在与CD46结合的病毒中，Ad35通常比Ad11更具细胞毒性。Ad5、Ad6和Ad11在体内表现出相似的抗癌活性，而Ad35则无效。肝毒性仅在注射Ad5的小鼠中出现。预先注射Ad11和Ad35并不会增加基于Ad5的载体对肝细胞的感染，这表明这些腺病毒与库普弗细胞的相互作用不同。本研究获得的数据表明，可将Ad6和Ad11开发为抗癌治疗的替代腺病毒。
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