美国俄亥俄州立大学的研究人员开发出一种全新的肿瘤攻击病毒(tumor-attacking virus),不但能够杀死大脑内的肿瘤细胞,还能够阻断肿瘤内血管的生长。该研究表明,这种能够杀死肿瘤的溶瘤病毒(oncolytic viruses)如果携带能够抑制血管生长的蛋白——vasculostatin,那么或许能够更有效的治疗侵润性脑部肿瘤。这项研究发表在Molecular Therapy杂志网络版上。
Vasculostatin蛋白通常产生于大脑中。研究人员发现,携带该蛋白的溶瘤细胞可以清除动物大脑中的人类胶质母细胞瘤,并且明显降低肿瘤的复发率。胶质母细胞瘤,是一种致命性的人类大脑癌症,该肿瘤中含有大量的血管,被诊断出患有这种癌症的患者通常存活时间不超过15个月。
这项研究表明,将溶瘤病毒和自然血管生长抑制因子如vasculostatin相结合或许是一种全新的肿瘤治疗方法。但目前还是需要进一步研究这种方法与化疗或放疗相结合治疗癌症的安全性和有效性。(生物谷Bioon.com)
生物谷推荐原始出处:
Molecular Therapy (2009); doi:10.1038/mt.2009.232
Enhanced Antitumor Efficacy of Vasculostatin (Vstat120) Expressing Oncolytic HSV-1
Jayson Hardcastle1,2, Kazuhiko Kurozumi1,, Nina Dmitrieva1, Martin P Sayers1,3, Sarwat Ahmad4, Peter Waterman5,6, Ralph Weissleder5,6, E Antonio Chiocca1 and Balveen Kaur1
1Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, James Comprehensive Cancer Center and The Ohio State University Medical Center, Columbus, Ohio, USA
2Integrated Biomedical Sciences Graduate Program, The Ohio State University Medical Center, Columbus, Ohio, USA
3Undergraduate Major in Biomedical Science, The Ohio State University Medical Center, Columbus, Ohio, USA
4College of Medicine, The Ohio State University Medical Center, Columbus, Ohio, USA
5Center for Molecular Imaging Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA
6Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
Oncolytic viral (OV) therapy is a promising therapeutic modality for brain tumors. Vasculostatin (Vstat120) is the cleaved and secreted extracellular fragment of brain-specific angiogenesis inhibitor 1 (BAI1), a brain-specific receptor. To date, the therapeutic efficacy of Vstat120 delivery into established tumors has not been investigated. Here we tested the therapeutic efficacy of combining Vstat120 gene delivery in conjunction with OV therapy. We constructed RAMBO (Rapid Antiangiogenesis Mediated By Oncolytic virus), which expresses Vstat120 under the control of the herpes simplex virus (HSV) IE4/5 promoter. Secreted Vstat120 was detected as soon as 4 hours postinfection in vitro and was retained for up to 13 days after OV therapy in subcutaneous tumors. RAMBO-produced Vstat120 efficiently inhibited endothelial cell migration and tube formation in vitro (P = 0.0005 and P = 0.0184, respectively) and inhibited angiogenesis (P = 0.007) in vivo. There was a significant suppression of intracranial and subcutaneous glioma growth in mice treated with RAMBO compared to the control virus, HSVQ (P = 0.0021 and P < 0.05, respectively). Statistically significant reduction in tumor vascular volume fraction (VVF) and microvessel density (MVD) was observed in tumors treated with RAMBO. This is the first study to report the antitumor effects of Vstat120 delivery into established tumors and supports the further development of RAMBO as a possible cancer therapy.