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首页 » BIOON报道 » J Virol. :科学家在小鼠模型中用病毒杀死黑色素瘤细胞

J Virol. :科学家在小鼠模型中用病毒杀死黑色素瘤细胞

来源:生物谷 2013-06-18 09:24

2013年6月18日讯 /生物谷BIOON/--发表在近期Journal of Virology杂志上的文章称,耶鲁大学科学家能够用快速复制的病毒杀死大多数黑色素瘤细胞。

黑色素瘤是一种致死性皮肤癌,能够遍布全身甚至到脑组织。

水疱性口炎病毒能够引起人感冒样病症。研究人员采用该病毒治疗黑色素瘤小鼠模型,该病毒无视健康黑色素细胞,但是能够杀死黑色素瘤细胞。在研究中的70%的小鼠模型所有的黑色素瘤都消失了,而其他的小鼠肿瘤也残留很少。

本文的通讯作者是耶鲁大学医学院神经外科学系教授Anthony N. van den Pol博士,van den Pol博士称将水疱性口炎病毒注入到小鼠血管中,病毒能够自己找的黑色素瘤细胞,快速侵入癌组织。由于病毒复制迅速,病毒能够杀死黑色素瘤,随后该病毒被免疫系统识别并被杀死。在病毒杀灭癌细胞的过程中,免疫系统也开始针对并杀灭癌细胞。

van den Pol博士补充道,如果该病毒足够安全,我们下一步打算在人类中开始测试该病毒对黑色素瘤细胞的效果。(生物谷Bioon.com)

Highly Attenuated Recombinant Vesicular Stomatitis Virus VSV-12′GFP Displays Immunogenic and Oncolytic Activity

van den Pol AN, Davis JN.

Vesicular stomatitis virus (VSV) has shown considerable promise both as an immunization vector and as an oncolytic virus. In both applications, an important concern is the safety profile of the virus. To generate a highly attenuated virus, we added two reporter genes to the 3′ end of the VSV genome, thereby shifting the NPMGL genes from positions 1 to 5 to positions 3 to 7. The resulting virus (VSV-12′GFP) was highly attenuated, generating smaller plaques than four other attenuated VSVs. In one-step growth curves, VSV-12′GFP displayed the slowest growth kinetics. The mechanism of attenuation appears to be due to reduced expression of VSV genes downstream of the reporter genes, as suggested by a 10.4-fold reduction in L-protein RNA transcript. Although attenuated, VSV-12′GFP was highly effective at generating an immune response, indicated by a high-titer antibody response against the green fluorescent protein (GFP) expressed by the virus. Although VSV-12′GFP was more attenuated than other VSVs on both normal and cancer cells, it nonetheless showed a greater level of infection of human cancer cells (glioma and melanoma) than of normal cells, and this effect was magnified in glioma by interferon application, indicating selective oncolysis. Intravenous VSV-12′GFP selectively infected human gliomas implanted into SCID mice subcutaneously or intracranially. All postnatal day 16 mice given intranasal VSV-12′GFP survived, whereas only 10% of those given VSV-G/GFP survived, indicating reduced neurotoxicity. Intratumoral injection of tumors with VSV-12′GFP dramatically suppressed tumor growth and enhanced survival. Together these data suggest this recombinant virus merits further study for its oncolytic and vaccine potential.

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