An acute toxicology study with INGN 007, an oncolytic adenovirus vector, in mice and permissive Syrian hamsters; comparisons with wild-type Ad5 and a replication-defective adenovirus vector.
An acute toxicology study with INGN 007, an oncolytic adenovirus vector, in mice and permissive Syrian hamsters; comparisons with wild-type Ad5 and a replication-defective adenovirus vector.
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DOI：
10.1038/cgt.2009.5
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发表时间：
2009-08
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
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溶瘤腺病毒作为抗癌药物为抗癌提供了新的、有前途的工具。为了支持I期临床试验，我们在此报告了INGN 007（VRX-007）的安全性数据，INGN 007是一种溶瘤腺病毒，由于腺病毒编码的ADP蛋白过表达，其抗肿瘤疗效增加。野生型腺病毒5型（Ad 5）和复制缺陷型的Ad 5也作为对照进行了研究。一项调查这些病毒生物分布的平行研究在本期其他地方进行了描述。毒理学实验在两个种属中进行，即允许INGN 007和Ad 5复制的叙利亚仓鼠和不允许复制的小鼠。研究表明，INGN 007的安全性特征与Ad 5相似。两种病毒在静脉注射后均引起一过性肝损伤，并在感染后28天消退。INGN 007在仓鼠中的无明显毒性作用水平（NOAEL）为3 × 1010个病毒颗粒/kg。在仓鼠中，复制缺陷型载体引起的毒性较小，表明Ad载体在宿主中的复制是致病的重要因素。对于小鼠，INGN 007和Ad 5引起的毒性与复制缺陷型腺病毒载体相当。部分基于这些结果，FDA批准INGN 007进入I期临床试验。
Oncolytic (replication-competent) adenoviruses as anticancer agents provide new, promising tools to fight cancer. In support of a Phase I clinical trial, here we report safety data with INGN 007 (VRX-007), an oncolytic adenovirus with increased anti-tumor efficacy due to overexpression of the adenovirus-encoded ADP protein. Wild-type adenovirus type 5 (Ad5) and a replication-defective version of Ad5 were also studied as controls. A parallel study investigating the biodistribution of these viruses is described elsewhere in this issue. The toxicology experiments were conducted in two species, the Syrian hamster, which is permissive for INGN 007 and Ad5 replication and the poorly permissive mouse. The studies demonstrated that the safety profile of INGN 007 is similar to Ad5. Both viruses caused transient liver damage upon intravenous injection that resolved by 28 days post-infection. The No-Observable-Adverse-Effect-Level (NOAEL) for INGN 007 in hamsters was 3 × 1010 viral particles per kg. In hamsters, the replication-defective vector caused less toxicity, indicating that replication of Ad vectors in the host is an important factor in pathogenesis. With mice, INGN 007 and Ad5 caused toxicity comparable to the replication-defective adenovirus vector. Partially based on these results, the FDA granted permission to enter into a Phase I clinical trial with INGN 007.
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影响因子：
4.2
作者：
Sauthoff, H;Hu, J;Hay, JG
通讯作者：
Hay, JG
DOI：
10.1038/nrmicro1927
发表时间：
2008-07
期刊：
Nature reviews. Microbiology
影响因子：
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影响因子：
12.4
作者：
Shashkova, Elena V.;Spencer, Jacqueline F.;Doronin, Konstantin
通讯作者：
Doronin, Konstantin
影响因子：
4.2
作者：
Toth, K;Spencer, JF;Wold, WSM
通讯作者：
Wold, WSM
DOI：
10.1038/mt.2008.162
发表时间：
2008-10
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
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