ATTENUATED MULTI-MUTATED HERPES-SIMPLEX VIRUS-1 FOR THE TREATMENT OF MALIGNANT GLIOMAS
ATTENUATED MULTI-MUTATED HERPES-SIMPLEX VIRUS-1 FOR THE TREATMENT OF MALIGNANT GLIOMAS
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DOI：
10.1038/nm0995-938
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发表时间：
1995-09-01
期刊：
影响因子：
82.9
通讯作者：
MARTUZA, RL
中科院分区：
文献类型：
--
作者：
MINETA, T;RABKIN, SD;MARTUZA, RL
我们已经创建了一个双突变体的单纯疱疹病毒（HSV）1型（称为G207）与治疗人类恶性脑肿瘤的有利性能：在胶质母细胞瘤细胞（和其他分裂细胞）的复制能力，减弱神经毒力，温度敏感性，更昔洛韦超敏反应，并存在一个容易检测的组织化学标记。G207在γ 34.5（RL 1）基因座和使ICP 6基因失活的lacZ基因插入（UL 39）处均具有缺失。G207在单层培养中杀死人胶质瘤细胞。在皮下或脑内U-87 MG胶质瘤的裸鼠中，瘤内接种G207可导致肿瘤生长减少和/或生存期延长。G207在脑内接种小鼠和HSV敏感的非人灵长类动物后是无毒的。这些结果表明，G207应考虑用于胶质母细胞瘤治疗的临床评价。
We have created a double mutant of the herpes simplex virus (HSV) type 1 (termed G207) with favourable properties for treating human malignant brain tumours: replication-competence in glioblastoma cells (and other dividing cells), attenuated neurovirulence, temperature sensitivity, ganciclovir hypersensitivity, and the presence of an easily detectable histochemical marker. G207 has deletions at both gamma 34.5 (RL1) loci and a lacZ gene insertion inactivating the ICP6 gene (UL39). G207 kills human glioma cells in monolayer cultures. In nude mice harbouring subcutaneous or intracerebral U-87MG gliomas, intraneoplastic inoculation with G207 causes decreased tumour growth and/or prolonged survival. G207 is avirulent upon intracerebral inoculation of mice and HSV-sensitive non-human primates. These results suggest that G207 should be considered for clinical evaluation in the treatment of glioblastomas.