Cancer Gene Therapy Group, Molecular Cancer Biology Program, University of Helsinki, P.O. Box 63, 00014 University of Helsinki, Finland.
HUSLAB , Helsinki University Central Hospital, P.O. Box 100, 00029 HUS, Helsinki, Finland.
Viruses. 2010 Oct;2(10):2196-2212. doi: 10.3390/v2102196. Epub 2010 Sep 30.
Cancer gene therapy consists of numerous approaches where the common denominator is utilization of vectors for achieving therapeutic effect. A particularly potent embodiment of the approach is virotherapy, in which the replication potential of an oncolytic virus is directed towards tumor cells to cause lysis, while normal cells are spared. Importantly, the therapeutic effect of the initial viral load is amplified through viral replication cycles and production of progeny virions. All cancer gene therapy approaches rely on a sufficient level of delivery of the anticancer agent into target cells. Thus, enhancement of delivery to target cells, and reduction of delivery to non-target cells, in an approach called transductional targeting, is attractive. Both genetic and non-genetic retargeting strategies have been utilized. However, in the context of oncolytic viruses, it is beneficial to have the specific modification included in progeny virions and hence genetic modification may be preferable. Serotype chimerism utilizes serotype specific differences in receptor usage, liver tropism and seroprevalence in order to gain enhanced infection of target tissue. This review will focus on serotype chimeric adenoviruses for cancer gene therapy applications.
癌症基因治疗包括许多方法，其共同点是利用载体来实现治疗效果。该方法的一个特别有效的体现是病毒疗法，其中溶瘤病毒的复制潜力被引导到肿瘤细胞以引起裂解，而正常细胞则幸免。重要的是，初始病毒载量的治疗效果通过病毒复制周期和产生的子代病毒颗粒得到放大。所有癌症基因治疗方法都依赖于将抗癌剂递送到靶细胞的足够水平。因此，在称为转导靶向的方法中，增强递送到靶细胞并减少递送到非靶细胞的水平是有吸引力的。已经利用了遗传和非遗传的再靶向策略。然而，在溶瘤病毒的情况下，有利的是在子代病毒颗粒中包含特异性修饰，因此遗传修饰可能是优选的。血清型嵌合利用受体利用、肝嗜性和血清流行率方面的血清型特异性差异，以获得靶组织的增强感染。本综述将重点介绍用于癌症基因治疗应用的血清型嵌合腺病毒。
