Cancer Res ：减活脊髓灰质炎病毒对成神经细胞瘤治疗有效
根据3月15日的《癌症研究》（Cancer Res 2007;67:2857-2864.）杂志上的一项报告，减活脊髓灰质炎病毒可以治疗有免疫小鼠的成神经细胞瘤。
美国Stony Brook大学的Eckard Wimmer博士及其同事培养出在成神经细胞瘤细胞内复制的稳定的减活脊髓灰质炎病毒(A133Gmono-crePV)，并在脊髓灰质炎病毒易感的成神经细胞瘤小鼠模型检查了这种病毒的作用。
作者报告，对4只非免疫小鼠单次瘤内注射A133Gmono-crePV，可在5天内引起肿瘤显著退化，但是半数小鼠发生瘫痪，并在一周内死亡。当相同的实验在对脊髓灰质炎病毒有免疫的小鼠进行时，使用A133Gmono-crePV治疗的所有12只小鼠均有明显的肿瘤退化，没有1只小鼠显示轻瘫和瘫痪。在180天时，11只A133Gmono-crePV治愈的小鼠中，9只没有肿瘤复发征象。由于肿瘤复发而再次治疗的2只小鼠没有出现肿瘤退化。6个月后使用成神经瘤细胞再接种时，A133Gmono-crePV治愈过的小鼠未发生肿瘤。
Wimmer博士说：“我们成功地治愈了抗脊髓灰质炎病毒免疫的小鼠。这为治疗抗脊髓灰质炎病毒免疫人类的肿瘤打开了一扇门。”但还有很长的路要走。在进行人类试验前需要在动物进行广泛的生物安全性检查。
部分英文原文：
Cancer Research 67, 2857-2864, March 15, 2007. doi: 10.1158/0008-5472.CAN-06-3713
Experimental Therapeutics, Molecular Targets, and Chemical Biology
Oncolytic Treatment and Cure of Neuroblastoma by a Novel Attenuated Poliovirus in a Novel Poliovirus-Susceptible Animal Model
Hidemi Toyoda, Jiang Yin, Steffen Mueller, Eckard Wimmer and Jeronimo Cello
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, New York
Requests for reprints: Eckard Wimmer, Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794-5222. E-mail: ewimmer@ms.cc.sunysb.edu .
Neuroblastoma is one of the most common solid tumors in children. Treatment is of limited utility for high-risk neuroblastoma and prognosis is poor. Resistance of neuroblastoma to conventional therapies has prompted us to search for a novel therapeutic approach based on genetically modified polioviruses. Poliovirus targets motor neurons leading to irreversible paralysis. Neurovirulence can be attenuated by point mutations or by exchange of genetic elements between different picornaviruses. We have developed a novel and stable attenuated poliovirus, replicating in neuroblastoma cells, by engineering an indigenous replication element (cre), copied from a genome-internal site, into the 5'-nontranslated genomic region (mono-crePV). An additional host range mutation (A133G) conferred replication in mouse neuroblastoma cells (Neuro-2aCD155) expressing CD155, the poliovirus receptor. Crossing immunocompetent transgenic mice susceptible to poliovirus (CD155 tg mice) with A/J mice generated CD155 tgA/J mice, which we immunized against poliovirus. Neuro-2aCD155 cells were then transplanted into these animals, leading to lethal tumors. Despite preexisting high titers of anti-poliovirus antibodies, established lethal s.c. Neuro-2aCD155 tumors in CD155 tgA/J mice were eliminated by intratumoral administrations of A133Gmono-crePV. No signs of paralysis were observed. Interestingly, no tumor growth was observed in mice cured of neuroblastoma that were reinoculated s.c. with Neuro-2aCD155. This result indicates that the destruction of neuroblastoma cells by A133Gmono-crePV may lead to a robust antitumor immune response. We suggest that our novel attenuated oncolytic poliovirus is a promising candidate for effective oncolytic treatment of human neuroblastoma or other cancer even in the presence of present or induced antipolio immunity. [Cancer Res 2007;67(6):2857–64]
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Cancer Research：脊髓灰质炎病毒可破坏小鼠成神经细胞瘤
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