脊髓灰質(zhì)炎病毒（小兒麻痹病毒）雖然是引起某種兒童疾病的罪魁禍?zhǔn)?，但可治療另一種兒童疾病——神經(jīng)母細(xì)胞瘤。根據(jù)一篇發(fā)表于3月15日Cancer Research期刊中的研究結(jié)果,， Stony Brook大學(xué)的研究人員利用一種無毒性的小兒麻痹病毒，有效去除了小鼠的神經(jīng)母細(xì)胞瘤,，即使小鼠曾經(jīng)接種過抵御小兒麻痹病毒的疫苗,，也具有療效。
小兒麻痹病毒會破壞受到感染的細(xì)胞,，復(fù)制出的病毒顆粒從細(xì)胞中釋放后,，再攻擊周圍細(xì)胞。
為了檢測病毒破壞神經(jīng)母細(xì)胞瘤的能力,，研究人員建立了一個(gè)攜帶人類CD155基因的神經(jīng)母細(xì)胞瘤轉(zhuǎn)基因小鼠模型,。然后給小鼠接種抵抗小兒麻痹病毒的疫苗。研究人員,，直接注射毒力已經(jīng)被削弱的小兒麻痹病毒,，結(jié)果病毒破壞了12只小鼠體內(nèi)的腫瘤，180天后有兩只小鼠的腫瘤復(fù)發(fā)。
病毒本身并未造成任何小鼠的副作用,。研究人員表示,，病毒顆粒進(jìn)入血流后會被小兒麻痹病毒疫苗產(chǎn)生的抗體消滅，如果應(yīng)用于人類,，可能會成為一種安全有效的治療致癌癥的措施,。
神經(jīng)母細(xì)胞瘤是四大常見兒童實(shí)體腫瘤之一，化療后經(jīng)常復(fù)發(fā),。這種腫瘤很難治愈,，化療不利于日后健康，小兒麻痹病毒治療可減少兒童接受化療和放療的次數(shù),，降低副作用,。
(資料來源 : Bio.com)
部分英文原文：
Cancer Research 67, 2857-2864, March 15, 2007. doi: 10.1158/0008-5472.CAN-06-3713
© 2007 American Association for Cancer Research
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]
