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携带内皮抑素-血管抑素融合基因的 Lister 疫苗株痘苗病毒:一种优于 dl1520(ONYX-015)的溶瘤病毒,用于治疗头颈部肿瘤。

Lister vaccine strain of vaccinia virus armed with the endostatin-angiostatin fusion gene: an oncolytic virus superior to dl1520 (ONYX-015) for human head and neck cancer.

机构信息

Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary of London, London EC1M 6BQ, United Kingdom.

出版信息

Hum Gene Ther. 2011 Sep;22(9):1101-8. doi: 10.1089/hum.2010.172. Epub 2011 Apr 18.

Abstract

Oncolytic viral therapy represents a promising strategy for the treatment of head and neck squamous cell carcinoma (HNSCC), with dl1520 (ONYX-015) the most widely used oncolytic adenovirus in clinical trials. This study aimed to determine the effectiveness of the Lister vaccine strain of vaccinia virus as well as a vaccinia virus armed with the endostatin-angiostatin fusion gene (VVhEA) as a novel therapy for HNSCC and to compare them with dl1520. The potency and replication of the Lister strain and VVhEA and the expression and function of the fusion protein were determined in human HNSCC cells in vitro and in vivo. Finally, the efficacy of VVhEA was compared with dl1520 in vivo in a human HNSCC model. The Lister vaccine strain of vaccinia virus was more effective than the adenovirus against all HNSCC cell lines tested in vitro. Although the potency of VVhEA was attenuated in vitro, the expression and function of the endostatin-angiostatin fusion protein was confirmed in HNSCC models both in vitro and in vivo. This novel vaccinia virus (VVhEA) demonstrated superior antitumor potency in vivo compared with both dl1520 and the control vaccinia virus. This study suggests that the Lister strain vaccinia virus armed with an endostatin-angiostatin fusion gene may be a potential therapeutic agent for HNSCC.

摘要

溶瘤病毒治疗代表了治疗头颈部鳞状细胞癌(HNSCC)的一种有前途的策略,其中 dl1520(ONYX-015)是临床试验中使用最广泛的溶瘤腺病毒。本研究旨在确定痘苗病毒李斯特菌株以及携带内皮抑素-血管抑素融合基因的痘苗病毒(VVhEA)作为治疗 HNSCC 的新型疗法的有效性,并将其与 dl1520 进行比较。在体外和体内的人 HNSCC 细胞中确定了李斯特株和 VVhEA 的效力和复制以及融合蛋白的表达和功能。最后,在人 HNSCC 模型中比较了 VVhEA 与 dl1520 的疗效。痘苗病毒李斯特疫苗株在体外对所有测试的 HNSCC 细胞系均比腺病毒更有效。尽管 VVhEA 的效力在体外减弱,但在体外和体内的 HNSCC 模型中均证实了内皮抑素-血管抑素融合蛋白的表达和功能。与 dl1520 和对照痘苗病毒相比,这种新型痘苗病毒(VVhEA)在体内显示出更强的抗肿瘤效力。本研究表明,携带内皮抑素-血管抑素融合基因的李斯特株痘苗病毒可能是治疗 HNSCC 的一种潜在治疗剂。

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