根據(jù)3月15日的《癌癥研究》（Cancer Res 2007;67:2857-2864.）雜志上的一項報告，減活脊髓灰質(zhì)炎病毒可以治療有免疫小鼠的成神經(jīng)細胞瘤,。
美國Stony Brook大學(xué)的Eckard Wimmer博士及其同事培養(yǎng)出在成神經(jīng)細胞瘤細胞內(nèi)復(fù)制的穩(wěn)定的減活脊髓灰質(zhì)炎病毒(A133Gmono-crePV)，并在脊髓灰質(zhì)炎病毒易感的成神經(jīng)細胞瘤小鼠模型檢查了這種病毒的作用,。
作者報告,，對4只非免疫小鼠單次瘤內(nèi)注射A133Gmono-crePV，可在5天內(nèi)引起腫瘤顯著退化,，但是半數(shù)小鼠發(fā)生癱瘓,，并在一周內(nèi)死亡。當相同的實驗在對脊髓灰質(zhì)炎病毒有免疫的小鼠進行時,，使用A133Gmono-crePV治療的所有12只小鼠均有明顯的腫瘤退化,，沒有1只小鼠顯示輕癱和癱瘓。在180天時,，11只A133Gmono-crePV治愈的小鼠中,，9只沒有腫瘤復(fù)發(fā)征象。由于腫瘤復(fù)發(fā)而再次治療的2只小鼠沒有出現(xiàn)腫瘤退化,。6個月后使用成神經(jīng)瘤細胞再接種時,，A133Gmono-crePV治愈過的小鼠未發(fā)生腫瘤。
Wimmer博士說：“我們成功地治愈了抗脊髓灰質(zhì)炎病毒免疫的小鼠,。這為治療抗脊髓灰質(zhì)炎病毒免疫人類的腫瘤打開了一扇門,。”但還有很長的路要走。在進行人類試驗前需要在動物進行廣泛的生物安全性檢查,。
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: [email protected] .
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]
