Biosafety studies of carrier cells infected with a replication-competent adenovirus introduced by IAI.3B promoter.
Biosafety studies of carrier cells infected with a replication-competent adenovirus introduced by IAI.3B promoter.
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DOI：
10.1038/mtm.2014.19
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发表时间：
2014
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影响因子：
--
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利用溶瘤病毒感染的载体细胞进行肿瘤基因治疗是一种有吸引力的方法，因为它可以克服病毒的免疫原性，诱导肿瘤免疫和显著的抗肿瘤活性。为了使这种治疗方法能够进行人体临床试验，必须首先进行急性和慢性毒性试验，以确保安全性。IAI. 3B启动子、由IAI. 3B启动子导入的溶瘤腺病毒AdE 3-IAI. 3B以及用AdE 3-IAI. 3B感染的A549载体细胞在癌细胞中具有高活性，而在正常细胞中不具有活性。冻融通过促进溶瘤腺病毒颗粒在核膜破裂后从细胞核移位到细胞质而增强A549载体细胞的抗肿瘤作用。裸小鼠单次给药后急性毒性试验未出现死亡或异常血液检查数据。在兔子慢性毒性试验中，在8次剂量为1.25 × 107个细胞/kg或更少的剂量持续4周后，没有严重的副作用;已知显著的免疫应答会引起抗腺病毒抗体数量增加并扩大脾脏。从这些结果可以得出结论，使用载体细胞的复发性实体瘤的癌症基因治疗可以在人类中安全地进行试验。
The use of carrier cells infected with oncolytic viruses in cancer gene therapy is an attractive method because it can overcome viral immunogenicity and induce tumor immunity and significant antitumor activity. To enable human clinical trials of this treatment, acute and chronic toxicity tests must first be performed to ensure safety. IAI.3B promoter, oncolytic adenovirus AdE3-IAI.3B introduced by IAI.3B promoter, and A549 carrier cells infected with AdE3-IAI.3B were highly active in cancer cells but not in normal cells. Freeze-thawing increased the antitumor effect of A549 carrier cells by promoting the translocation of oncolytic adenovirus particles from the nucleus to the cytoplasm following the rupture of the nuclear membranes. No deaths or abnormal blood test data resulted from acute toxicity tests conducted in nude mice after a single dose. In chronic toxicity tests in rabbits, there were no serious side effects after eight doses of 1.25 × 107 cells/kg or less for 4 weeks; a significant immune response is known to elicit increased numbers of antiadenovirus antibodies and enlarge the spleen. From these results, it could be concluded that cancer gene therapy of recurrent solid tumors using carrier cells can be safely trialed in humans.
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影响因子：
2.1
作者：
Terao, Shuji;Shirakawa, Toshiro;Gotoh, Akinobu
通讯作者：
Gotoh, Akinobu
影响因子：
4.2
作者：
Jooss, K;Yang, YP;Wilson, JM
通讯作者：
Wilson, JM
影响因子：
4.2
作者：
Li, Yan;Shao, Jian-Yong;Huang, Wenlin
通讯作者：
Huang, Wenlin
影响因子：
6.4
作者：
Raykov, Z;Balboni, G;Rommelaere, J
通讯作者：
Rommelaere, J
影响因子：
3.3
作者：
Steel, JC;Cavanagh, HMA;Kalle, WHJ
通讯作者：
Kalle, WHJ