溶瘤甲病毒SFV-VA7能有效根除小鼠皮下和原位人类前列腺肿瘤。
Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice.
作者信息
Martikainen Miika, Ruotsalainen Janne, Tuomela Johanna, Härkönen Pirkko, Essand Magnus, Heikkilä Jari, Hinkkanen Ari
机构信息
Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio 70211, Finland.
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala 75237, Sweden.
出版信息
Br J Cancer. 2017 Jun 27;117(1):51-55. doi: 10.1038/bjc.2017.151. Epub 2017 May 30.
BACKGROUND
Despite recent therapeutic and diagnostic advances, prostate cancer remains the second leading cause of cancer-related deaths among men in the Western world. Oncolytic viruses that replicate selectively in tumour cells represent a novel treatment candidate for these malignancies.
METHODS
We analysed infectivity of avirulent Semliki Firest virus SFV-VA7 in human prostate cancer cell lines VCaP, LNCaP and 22Rv1 and in nonmalignant prostate epithelial cell line RWPE-1. Therapeutic potency of SFV-VA7 was evaluated in subcutaneous and orthotopic mouse LNCaP xenograft models.
RESULTS
SFV-VA7 infected and killed the tested human prostate cancer cell lines irrespective of their hormone response status, while the nonmalignant prostate epithelial cell line RWPE-1 proved highly virus resistant. Notably, a single peritoneal dose of SFV-VA7 was sufficient to eradicate all subcutaneous and orthotopic LNCaP tumours.
CONCLUSIONS
Our results indicate that SFV-VA7 is a novel, promising therapeutic virus against prostate cancer warranting further testing in early clinical trials.
背景
尽管近期在治疗和诊断方面取得了进展，但前列腺癌仍是西方世界男性癌症相关死亡的第二大主要原因。在肿瘤细胞中选择性复制的溶瘤病毒是这些恶性肿瘤的一种新型治疗候选方案。
方法
我们分析了无毒力的Semliki森林病毒SFV-VA7对人前列腺癌细胞系VCaP、LNCaP和22Rv1以及非恶性前列腺上皮细胞系RWPE-1的感染性。在皮下和原位小鼠LNCaP异种移植模型中评估了SFV-VA7的治疗效力。
结果
SFV-VA7感染并杀死了所测试的人前列腺癌细胞系，无论其激素反应状态如何，而非恶性前列腺上皮细胞系RWPE-1对该病毒具有高度抗性。值得注意的是，单次腹腔注射SFV-VA7足以根除所有皮下和原位LNCaP肿瘤。
结论
我们的结果表明，SFV-VA7是一种新型的、有前景的抗前列腺癌治疗病毒，值得在早期临床试验中进一步测试。
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