Replication-selective adenoviruses as oncolytic agents
Replication-selective adenoviruses as oncolytic agents
复制标题
DOI：
10.1172/jci9762
复制
发表时间：
2000-04-01
影响因子：
15.9
通讯作者：
Kirn, DH
中科院分区：
文献类型：
--
作者：
Heise, C;Kirn, DH
大卫H. Kirn，Editor肿瘤细胞可以通过几种机制引起细胞破坏（表1）。首先，在感染过程后期表达的病毒蛋白，包括E3 11.6腺病毒死亡蛋白（16）和E4 ORF 4（17），具有直接的细胞毒性。相应基因的缺失显著延迟了受感染细胞的死亡。此外，在腺病毒生命周期早期E1 A的表达使细胞对肿瘤坏死因子（TNF）介导的杀伤敏感（18）。E3蛋白10.4/14.5和14.7可抑制这种作用;这些E3蛋白的缺失导致体内TNF表达增加，并增强细胞对TNF的敏感性。最后，在模型系统中，病毒在肿瘤细胞中的复制和肿瘤细胞的裂解诱导细胞介导的对肿瘤细胞的免疫（R.马图扎，这个系列）。患者是否会受益于类似的效果仍有待确定。
David H. Kirn, Editor tumor cell can cause cell destruction by several mechanisms (Table 1). First, viral proteins, including the E3 11.6 adenovirus death protein (16) and E4ORF4 (17), that are expressed late in the course of infection are directly cytotoxic. Deletion of the corresponding genes significantly delays death of infected cells. In addition, expression of E1A early during the adenovirus lifecycle sensitizes cells to tumor necrosis factor (TNF)-mediated killing (18). This effect is inhibited by the E3 proteins 10.4/14.5 and 14.7; deletion of these E3 proteins leads to an increase in TNF expression in vivo and enhanced cell sensitivity to TNF. Finally, viral replication in and lysis of tumor cells induces cell-mediated immunity to tumor cells in model systems (R. Martuza, this series). Whether patients will benefit from a similar effect remains to be determined.