用于治疗头颈部鳞状细胞癌的融合性水疱性口炎病毒
Fusogenic vesicular stomatitis virus for the treatment of head and neck squamous carcinomas.
作者信息
Shin Edward J, Chang Jaime I, Choi Bryan, Wanna Georges, Ebert Oliver, Genden Eric M, Woo Savio L C
机构信息
Department of Otolaryngology--Head and Neck Surgery, Mount Sinai School of Medicine, New York, NY 10029, USA.
出版信息
Otolaryngol Head Neck Surg. 2007 May;136(5):811-7. doi: 10.1016/j.otohns.2006.11.046.
OBJECTIVES
This study investigates the efficacy of recombinant fusogenic VSV [rVSV-NDV/F(L289A) or rVSV-F] in the treatment of head and neck squamous cell carcinoma (HNSCC).
STUDY DESIGN AND SETTING
The in vitro replication and cytotoxicity of rVSV-F were studied in two human SCC cell lines, in one murine SCC cell line, and in human keratinocytes. The effects on tumor size and animal survival were investigated following in vivo rVSV-F treatment of floor-of-mouth tumor model C3H/HeJ mice.
RESULTS
Recombinant VSV-F preferentially induced rapid syncytia formation, and replicated in (P < 0.04) and killed (P < 1 x 10(-13)) all three SCC lines tested. The virus had no observable effect on human keratinocytes. Tumor size was smaller (P < 0.03) and overall survival was better (P < 0.001) for treated animals than for control animals.
CONCLUSION/SIGNIFICANCE: Recombinant VSV-F confers a modest survival benefit for HNSCC in this orthotopic murine model. This oncolytic virus holds promise as a novel cancer treatment for recurrent HNSCC.
目的
本研究调查重组融合性水疱性口炎病毒[rVSV-NDV/F(L289A)或rVSV-F]治疗头颈部鳞状细胞癌（HNSCC）的疗效。
研究设计与环境
在两个人类鳞状细胞癌细胞系、一个小鼠鳞状细胞癌细胞系和人类角质形成细胞中研究rVSV-F的体外复制和细胞毒性。在用rVSV-F对口腔底部肿瘤模型C3H/HeJ小鼠进行体内治疗后，研究其对肿瘤大小和动物存活的影响。
结果
重组VSV-F优先诱导快速合胞体形成，并在所有三种测试的鳞状细胞癌细胞系中复制（P < 0.04）并杀死（P < 1×10⁻¹³）这些细胞系。该病毒对人类角质形成细胞没有可观察到的影响。与对照动物相比，治疗动物的肿瘤尺寸更小（P < 0.03），总体存活率更高（P < 0.001）。
结论/意义：在这种原位小鼠模型中，重组VSV-F为HNSCC带来适度的生存益处。这种溶瘤病毒有望成为复发性HNSCC的一种新型癌症治疗方法。
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