Noninvasive dual modality in vivo monitoring of the persistence and potency of a tumor targeted conditionally replicating adenovirus
Noninvasive dual modality in vivo monitoring of the persistence and potency of a tumor targeted conditionally replicating adenovirus
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DOI：
10.1038/sj.gt.3302387
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发表时间：
2005-01-01
期刊：
影响因子：
5.1
通讯作者：
Hemminki, A
中科院分区：
文献类型：
--
作者：
Kanerva, A;Zinn, KR;Hemminki, A
在癌症患者的临床试验中，条件复制腺病毒（CRAds）的安全性良好。然而，关于这些药物的持久性或抗肿瘤疗效的数据有限。CRAd的溶瘤效力由其进入靶细胞的能力决定。因此，我们构建了一个重靶向的CRAd，其特征在于分泌的标记蛋白，可溶性人癌胚抗原（hCEA），可以在生长培养基或血浆中测量。我们发现，病毒复制密切相关的hCEA分泌在体外和体内。此外，抗肿瘤功效和病毒的持久性可以从血浆hCEA水平推断。最后，使用体内生物发光成像，我们能够检测到病毒对肿瘤细胞的有效杀伤，从而提高了治疗效果。
In clinical trials with cancer patients, the safety of conditionally replicating adenoviruses (CRAds) has been good. However, marginal data are available on the persistence or antitumor efficacy of these agents. The oncolytic potency of CRAds is determined by their capacity for entering target cells. Consequently, we constructed a retargeted CRAd featuring a secreted marker protein, soluble human carcinoembryogenic antigen (hCEA), which can be measured in growth medium or plasma. We found that virus replication closely correlated with hCEA secretion both in vitro and in vivo. Further, antitumor efficacy and the persistence of the virus could be deduced from plasma hCEA levels. Finally, using in vivo bioluminescence imaging, we were able to detect effective tumor cell killing by the virus, which led to enhanced therapeutic efficacy.