Treatment of prostate cancer with Ad5/3Δ24hCG allows non-invasive detection of the magnitude and persistence of virus replication in vivo
Treatment of prostate cancer with Ad5/3Δ24hCG allows non-invasive detection of the magnitude and persistence of virus replication in vivo
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DOI：
10.1158/1535-7163.mct-06-0403
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发表时间：
2007-02-01
影响因子：
5.7
通讯作者：
Hemminki, Akseli
中科院分区：
文献类型：
--
作者：
Rajecki, Maria;Kanerva, Anna;Hemminki, Akseli
激素难治性转移性前列腺癌是一种致命的疾病，目前缺乏治愈性治疗。连续复制型腺病毒（CRAd）由于其固有的导致肿瘤细胞溶解的能力而成为有希望的抗肿瘤新药物。它们的抗肿瘤作用部分取决于它们感染癌细胞的能力。然而，相应的主要受体，柯萨奇-腺病毒受体（CAR），在许多癌症类型中不稳定表达。我们创建了Ad 5/3A 24 hCG，一种新的CRAd重靶向腺病毒血清型3受体，据报道该受体在肿瘤中高度表达。此外，我们添加了人绒毛膜促性腺激素（hCGO）的P链的转基因，其表达与病毒复制紧密耦合。发现Ad 5/3A 24 hCG有效杀死前列腺癌细胞，并且溶瘤作用与hCG产生一致。在一个s.c.在激素难治性前列腺癌的体内模型中，Ad 5/3A 24 hCG治疗导致统计学上显著的肿瘤生长抑制。
Hormone refractory metastatic prostate cancer is a deadly disease that currently lacks curative treatments. Conditionally replicating adenoviruses (CRAds) are promising new agents against cancer due to their innate capability to cause oncolysis of tumor cells. Their antitumor effect is determined in part by their capacity for infecting cancer cells. However, the respective primary receptor, the coxsackie-adenovirus receptor (CAR), is variably expressed in many cancer types. We created Ad5/3A24hCG, a novel CRAd retargeted to the adenovirus serotype 3 receptor, which has been reported to be highly expressed in tumors. Furthermore, we added a transgene for the P-chain of human chorionic gonadotropin (hCGO), whose expression was tightly coupled to virus replication. Ad5/3A24hCG was found effective in killing prostate cancer cells, and oncolysis was seen in concordance with hCG production. In a s.c. in vivo model of hormone refractory prostate cancer, Ad5/3A24hCG treatment resulted in statistically significant tumor growth inhibition.