脊髓灰质炎病毒(小儿麻痹病毒)虽然是引起某种儿童疾病的罪魁祸首,但可治疗另一种儿童疾病——神经母细胞瘤。根据一篇发表于3月15日Cancer Research期刊中的研究结果, Stony Brook大学的研究人员利用一种无毒性的小儿麻痹病毒,有效去除了小鼠的神经母细胞瘤,即使小鼠曾经接种过抵御小儿麻痹病毒的疫苗,也具有疗效。
小儿麻痹病毒会破坏受到感染的细胞,复制出的病毒颗粒从细胞中释放后,再攻击周围细胞。
为了检测病毒破坏神经母细胞瘤的能力,研究人员建立了一个携带人类CD155基因的神经母细胞瘤转基因小鼠模型。然后给小鼠接种抵抗小儿麻痹病毒的疫苗。研究人员,直接注射毒力已经被削弱的小儿麻痹病毒,结果病毒破坏了12只小鼠体内的肿瘤,180天后有两只小鼠的肿瘤复发。
病毒本身并未造成任何小鼠的副作用。研究人员表示,病毒颗粒进入血流后会被小儿麻痹病毒疫苗产生的抗体消灭,如果应用于人类,可能会成为一种安全有效的治疗致癌症的措施。
神经母细胞瘤是四大常见儿童实体肿瘤之一,化疗后经常复发。这种肿瘤很难治愈,化疗不利于日后健康,小儿麻痹病毒治疗可减少儿童接受化疗和放疗的次数,降低副作用。
(资料来源 : 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: 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]