Intergeneric poliovirus recombinants for the treatment of malignant glioma
Intergeneric poliovirus recombinants for the treatment of malignant glioma
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DOI：
10.1073/pnas.97.12.6803
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发表时间：
2000-06-06
影响因子：
11.1
通讯作者：
Wimmer, E
中科院分区：
文献类型：
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作者：
Gromeier, M;Lachmann, S;Wimmer, E
脊髓灰质炎病毒的神经致病性取决于病毒5'非翻译区内的序列。脊髓灰质炎病毒内部核糖体进入位点与人鼻病毒2型对应物的交换导致灵长类动物神经毒力减弱。尽管神经元来源的细胞中病毒繁殖缺陷，但非致病性脊髓灰质炎重组体在神经胶质肿瘤来源的细胞系中保留了优异的生长特性。恶性胶质瘤细胞对脊髓灰质炎病毒的易感性可能是通过脊髓灰质炎病毒受体CD155的表达介导的。神经胶质肿瘤。具有异源内部核糖体进入位点元件的属间脊髓灰质炎重组体在无胸腺小鼠中对实验诱导的神经胶质瘤展现了强大的溶瘤潜力。我们的观察表明，高度减毒的脊髓灰质炎病毒重组体可能具有作为生物抑制剂的适用性。
Poliovirus neuropathogenicity depends on sequences within the 5' nontranslated region of the virus. Exchange of the poliovirus internal ribosomal entry site with its counterpart from human rhinovirus type 2 resulted in attenuation of neurovirulence in primates. Despite deficient virus propagation in cells of neuronal origin, nonpathogenic polio recombinants retain excellent growth characteristics in cell lines derived from glial neoplasms. Susceptibility of malignant glioma cells to poliovirus may be mediated by expression of a poliovirus receptor, CD155. in glial neoplasms. Intergeneric polio recombinants with heterologous internal ribosomal entry site elements unfolded strong oncolytic potential against experimentally induced gliomas in athymic mice. Our observations suggest that highly attenuated poliovirus recombinants may have applicability as biotherapeutic antineoplastic agents.