Differential susceptibility of pediatric sarcoma cells to oncolysis by conditionally replication-competent herpes simplex viruses
Differential susceptibility of pediatric sarcoma cells to oncolysis by conditionally replication-competent herpes simplex viruses
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DOI：
10.1097/00043426-200208000-00008
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发表时间：
2002-08-01
影响因子：
1.2
通讯作者：
Cripe, TP
中科院分区：
文献类型：
--
作者：
Bharatan, NS;Currier, MA;Cripe, TP
目的：源自 I 型单纯疱疹病毒 (HSV) 的减毒病毒可杀死肿瘤细胞（溶瘤），目前正处于针对选定癌症（主要是癌和神经胶质瘤）的临床试验中。作者试图确定儿科肉瘤细胞是否也对 HSV 介导的溶瘤作用敏感。 材料和方法：作者测试了一组来自横纹肌肉瘤、骨肉瘤、尤文肉瘤和继发性恶性纤维组织细胞瘤的 10 个细胞系在暴露于减毒 HSV 载体后的存活率。使用的病毒包括NV1020（神经毒力基因ICP34.5的单倍体）和G207（缺失ICP34.5和核糖核苷酸还原酶但表达β-半乳糖苷酶报告基因）。 G207 转导通过测量 β-半乳糖苷酶表达来确定。结果：肉瘤细胞对病毒溶瘤的敏感性不同，但组织学类型相对一致。横纹肌肉瘤和恶性纤维组织细胞瘤细胞对两种HSV重组体的溶瘤作用最敏感，而骨肉瘤细胞对两种HSV重组体的溶瘤作用中等敏感。尽管尤文肉瘤细胞显示出有效的病毒进入和基因转移，但这些细胞对 HSV 溶瘤最不敏感。结论：具有条件复制能力的 HSV 衍生载体可能可用于治疗横纹肌肉瘤和骨肉瘤，但在确定并规避耐药机制之前，可能无法有效治疗尤文肉瘤。
Purpose: Attenuated viruses derived from herpes simplex virus (HSV) type I that kill tumor cells (oncolysis) are currently in clinical trials for selected cancers, primarily carcinomas and gliomas. The authors sought to determine if pediatric sarcoma cells are also sensitive to HSV-mediated oncolysis.Materials and Methods: The authors tested a panel of ten cell lines derived from rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, and a secondary malignant fibrous histiocytoma for survival after exposure to attenuated HSV vectors. The viruses used included NV1020, haploid for the neurovirulence gene ICP34.5, and G207, deleted for both ICP34.5 and ribonucleotide reductase but expressing the beta-galactosidase reporter gene. G207 transduction was determined by measuring beta-galactosidase expression.Results: Sarcoma cells differed in their sensitivity to viral oncolysis but were relatively consistent by histologic type. Rhabdomyosarcoma and malignant fibrous histiocytoma cells were most sensitive while osteosarcoma cells were intermediately sensitive to oncolysis by both HSV recombinants. Although Ewing sarcoma cells showed efficient viral entry and gene transfer, these cells were the least susceptible to oncolysis by HSV.Conclusions: Conditionally replication-competent HSV-derived vectors may be useful for the treatment of rhabdomyosarcoma and osteosarcoma, but may not be as efficacious for treating Ewing sarcoma until the mechanism of resistance is defined and circumvented.