加拿大戴尔豪斯医学院癌症研究人员帕特里克﹒李博士证明,一种普通的病毒可以感染并杀死癌症干细胞。这一突破性发现发表在最近出版的美国基因疗法学会杂志《分子疗法》上。
科学界近几年才刚认识到癌症干细胞的作用,并迫切需要找到一种清除它的办法。“癌症干细胞是一种母细胞。”李博士解释说。“它们不断产生新的癌细胞并形成肿瘤。”由于癌症干细胞对化疗和放疗不敏感,因此要杀死它们非常困难。就像李博士所说,“我们可以杀死肿瘤里的所有常规癌细胞,但只要存在癌症干细胞,癌症就会复发。”
“我们认为呼肠孤病毒能有效杀死癌症干细胞,因为我们反复发现它能有效杀死常规癌细胞。”李博士说。他是世界上第一位发现一种良性自然病毒能有选择感染并杀死癌细胞而不损害健康细胞的人。加拿大一家生物技术公司对呼肠孤病毒进行临床试验发现,这种治疗安全而有效。
与大多数利用试验室培养癌细胞的研究不同,这次研究所用的是从患者身上切除的新鲜乳腺癌组织。
呼肠孤病毒除了具有杀死癌细胞和癌症干细胞的能力外,还能激发抗癌的免疫系统。由于这种治疗也能诱导抗癌反应,李博士和同事正在研究一种方法,在病毒感染并摧毁癌症细胞的同时能加强免疫系统抗击癌细胞的能力。“我们下一步工作就是让这种双重治疗的方法能够成熟。”李博士说。“我们要利用呼肠孤病毒固有的特点和免疫系统自身优势开发一种强有力的、基于病毒的抗癌疗法。”
呼肠孤病毒有效针对癌症干细胞这一研究发现已引起英国LeadDiscovery制药公司的注意,他们准备进行这一方面的药物研发。(生物谷Bioon.com)
生物谷推荐原始出处:
Molecular Therapy (2009); doi:10.1038/mt.2009.58
Oncolytic Reovirus Effectively Targets Breast Cancer Stem Cells
Paola Marcato1, Cheryl A Dean1, Carman A Giacomantonio2 and Patrick WK Lee1,3
1Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
2Department of Surgery, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
3Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Abstract
Recent evidence suggests that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are resistant to current anticancer therapies. Hence, novel cancer therapies will need to be tested for both tumor regression and CSC targeting. Herein we show that oncolytic reovirus that induces regression of human breast cancer primary tumor samples xenografted in immunocompromised mice also effectively targets and kills CSCs in these tumors. CSCs were identified based on CD24-CD44+ cell surface expression and overexpression of aldehyde dehydrogenase. Upon reovirus treatment, the CSC population was reduced at the same rate as non-CSCs within the tumor. Immunofluorescence of breast tumor tissue samples from the reovirus- and mock-treated mice confirmed that both CSCs and non-CSCs were infectible by reovirus, and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay showed that both populations died by apoptosis. Ras, which has been shown to mediate reovirus oncolysis, was found to be present at similar levels in all cell types, and this is consistent with their comparable sensitivity to reovirus. These experiments indicate that oncolytic reovirus has the potential to induce tumor regression in breast cancer patients. More important, the CSC population was equally reduced and was as susceptible to reovirus treatment as the non-CSC population.