Carrier cell-mediated delivery of oncolytic parvoviruses for targeting metastases
Carrier cell-mediated delivery of oncolytic parvoviruses for targeting metastases
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DOI：
10.1002/ijc.20013
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发表时间：
2004-05-01
影响因子：
6.4
通讯作者：
Rommelaere, J
中科院分区：
文献类型：
--
作者：
Raykov, Z;Balboni, G;Rommelaere, J
在过去的几年里，天然存在的或基因操纵的溶瘤病毒作为癌症治疗的新疗法获得了越来越多的关注。本工作提供了一种基于亲器官细胞的载体系统适合于将溶瘤细小病毒递送至已知为转移瘤形成靶点的组织的原理证明。感染后通过γ-照射灭活载体细胞，发现其不影响能够裂解共培养的靶肿瘤细胞的细小病毒的产生和释放。虽然系统给予细小病毒H-I对已建立的Morris肝癌（MH 3924 A）肺转移的发展显示出明显的治疗效果，但载体细胞策略提供了许多优势。感染的携带者能够在受转移性疾病影响的大鼠的肺中维持H-I病毒表达6天，并减少病毒向外周器官的扩散。与直接病毒注射相比，载体细胞方案导致改善的治疗效果（转移抑制）和更少的病毒中和抗体的产生。这些数据支持使用载体细胞将溶瘤病毒和/或病毒载体局部递送到肿瘤中，更具体地，转移灶中。(C)2004 Wiley-Liss，Inc.
Over the last few years, naturally occurring or genetically manipulated oncolytic viruses gained increasing attention as novel therapeutics for cancer treatment. The present work provides proof of principle that an organotropic cell-based carrier system is suitable to deliver oncolytic parvoviruses to a tissue known to be a target for the formation of metastases. Carrier cells were inactivated by gamma-irradiation after infection, which was found not to affect the production and release of parvoviruses that were capable of lysing cocultured target neoplastic cells. Although systemically administered parvovirus H-I showed a pronounced therapeutic effect against the development of established Morris hepatoma (MH3924A) lung metastases, the carrier cell strategy offered a number of advantages. Infected carriers were able to sustain H-I virus expression for 6 days in the lungs of rats affected by metastatic disease and to reduce the spreading of the virus to peripheral organs. Compared to direct virus injection, the carrier cell protocol led to an improved therapeutic effect (metastases suppression) and a lesser generation of virus-neutralizing antibodies. These data support the use of carrier cells to deliver oncolytic viruses and/or viral vectors locally in tumors and, more particularly, metastases. (C) 2004 Wiley-Liss, Inc.