Intravenous administration of ONYX-015, a selectively replicating adenovirus, induces antitumoral efficacy.
Intravenous administration of ONYX-015, a selectively replicating adenovirus, induces antitumoral efficacy.
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发表时间：
1999-06
期刊：
影响因子：
11.2
通讯作者：
Carla Heise;Angelica Williams;Shirley Xue;Meisa Propst;D. Kirn
中科院分区：
文献类型：
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作者：
Carla Heise;Angelica Williams;Shirley Xue;Meisa Propst;D. Kirn
不能复制的病毒载体正在被开发用于癌症的基因治疗。虽然其中一些可能最终被证明具有显著的局部抗肿瘤活性，但迄今为止还没有一种显示在静脉注射后感染并导致已建立的肿瘤消退。由于癌症是一种全身性疾病，在几乎所有的致命病例中，缺乏静脉注射的疗效是用复制能力不足的病毒载体治疗的主要限制。ONYX-015 （d11520）是一种减毒腺病毒，在癌细胞中复制并导致选择性裂解。我们在裸鼠体内进行了s.c.和异种肝实质内肿瘤移植的静脉注射疗效和分布研究。ONYX-015在静脉给药后在肿瘤内有效感染和复制。给药后3小时肝脏中的病毒滴度相对较高，但迅速下降，24小时后无法检测到。有效的抗肿瘤剂量与肝毒性无关。在几种肿瘤模型中，肿瘤内的病毒复制与回归相关。选择性复制像ONYX-015这样的病毒有望成为治疗转移性癌症的药物。
Replication-incompetent viral vectors are being developed for the gene therapy of cancer. Although some of these may eventually be proven to have significant localized antitumoral activity, none to date have been shown to infect and cause regression of established tumors following i.v. administration. Because cancer is a systemic disease in almost all fatal cases, the lack of i.v. efficacy is a major limitation to treatment with replication-incompetent viral vectors. ONYX-015 (d11520) is an attenuated adenovirus that replicates in and causes selective lysis of cancer cells. We carried out i.v. efficacy and distribution studies in nude mice with s.c. and intraparenchymal tumor xenografts. ONYX-015 infected and replicated efficiently within tumors following i.v. administration. Viral titers in livers were relatively high 3 h after administration but decreased rapidly, becoming undetectable after 24 h. Effective antitumor doses were not associated with hepatic toxicity. Viral replication within tumors was associated with regressions in several tumor models. Selectively replicating viruses like ONYX-015 hold promise as agents to treat metastatic cancer.