INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studies.
INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studies.
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DOI：
10.1038/cgt.2009.6
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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：
--
作者：
在允许Ad复制的叙利亚仓鼠和小鼠中进行了INGN 007（一种溶瘤腺病毒（Ad）载体）的临床前生物分布研究，支持早期临床试验，小鼠是评估复制缺陷型（RD）Ad载体毒性和生物分布的标准模型。在跨越1年的5个时间点，通过实时PCR在9个组织和血液中检查静脉给药后的载体传播和药代动力学。还检查了选定器官是否存在感染性载体/病毒。在仓鼠模型中比较了INGN 007（VRX-007）、野生型Ad 5和AdCMVpA（一种RD载体），而在小鼠中仅检查了INGN 007。所有载体的DNA在注射后早期广泛传播，但在大多数器官中迅速衰减。在仓鼠模型中，INGN 007和Ad 5的DNA在注射后早期比RD载体AdCMVpA的DNA更丰富，但随后观察到相似的水平。注射后早期某些器官中INGN 007和Ad 5 DNA水平升高，但AdCMVpA DNA水平未升高，以及注射后早期肺和肝脏样本中存在感染性INGN 007和Ad 5，强烈表明INGN 007和Ad 5在几个叙利亚仓鼠器官中发生复制。没有证据表明INGN 007在小鼠中复制。除了提供关于INGN 007的重要信息外，结果强调了叙利亚仓鼠作为Ad 5发病机制和溶瘤Ad载体的容许免疫活性模型的实用性。
Preclinical biodistribution studies with INGN 007, an oncolytic adenovirus (Ad) vector, supporting an early stage clinical trial were conducted in Syrian hamsters, which are permissive for Ad replication, and mice, which are a standard model for assessing toxicity and biodistribution of replication-defective (RD) Ad vectors. Vector dissemination and pharmacokinetics following intravenous administration were examined by real-time PCR in nine tissues and blood at five time points spanning 1 year. Select organs were also examined for the presence of infectious vector/virus. INGN 007 (VRX-007), wild-type Ad5 and AdCMVpA (an RD vector) were compared in the hamster model, whereas only INGN 007 was examined in mice. DNA of all vectors was widely disseminated early after injection, but decayed rapidly in most organs. In the hamster model, DNA of INGN 007 and Ad5 was more abundant than that of the RD vector AdCMVpA at early times after injection, but similar levels were seen later. An increased level of INGN 007 and Ad5 DNA but not AdCMVpA DNA in certain organs early after injection, and the presence of infectious INGN 007 and Ad5 in lung and liver samples at early times after injection, strongly suggests that replication of INGN 007 and Ad5 occurred in several Syrian hamster organs. There was no evidence of INGN 007 replication in mice. In addition to providing important information about INGN 007, the results underscore the utility of the Syrian hamster as a permissive immunocompetent model for Ad5 pathogenesis and oncolytic Ad vectors.
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