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Oncolytic Herpes Simplex Virus Prevents Premalignant Lesions from Progressing to Cancer.
Molecular Therapy: Oncology ( IF 5.3 ) Pub Date : 2019-12-06 , DOI: 10.1016/j.omto.2019.11.003
Yanghee Woo 1, 2 , Vincent Reid 1, 3 , Kaitlyn J Kelly 1, 4 , Diane Carlson 5 , Zhenkun Yu 1, 6 , Yuman Fong 1, 2
Affiliation  

Early detection and timely treatment of precancerous lesions are hallmarks of successful strategies to prevent deaths due to cancer. Oncolytic viruses are a group of promising anti-cancer agents with wide-ranging experimental and clinical efficacy against solid tumors. Previously, we have shown that NV1066, an oncolytic herpes simplex-1 virus encoding enhanced green fluorescent protein, selectively infects, replicates in, and kills various cancer types. In this study, we sought to determine whether this oncolytic agent can treat precancerous lesions to prevent cancer formation. Using an oral chemical carcinogenesis model in hamsters, we assessed the ability of NV1066 to infect precancerous and cancerous lesions. NV1066 consistently infected dysplastic cells, carcinoma in situ, and squamous cell carcinoma. Animals receiving an intramucosal injection of NV1066 for 7 weeks showed significantly fewer (3-fold) and smaller (4-fold) lesions compared to animals that did not receive viral treatment. Results indicate that infectivity might be dependent on the herpes simplex virus 1 receptor, nectin-1. This study demonstrates that not only can NV1066 treat oral squamous cell carcinoma, but it can also infect and treat premalignant lesions, thus delaying cancer progression. Overall, our study shows the potential of the oncolytic virus NV1066 as a cancer prevention tool.



中文翻译:


溶瘤单纯疱疹病毒可防止癌前病变进展为癌症。



早期发现并及时治疗癌前病变是预防癌症死亡策略成功的标志。溶瘤病毒是一组有前途的抗癌药物,对实体瘤具有广泛的实验和临床功效。此前,我们已经证明,NV1066(一种编码增强型绿色荧光蛋白的溶瘤单纯疱疹病毒 1)能够选择性感染、复制并杀死多种癌症类型。在这项研究中,我们试图确定这种溶瘤剂是否可以治疗癌前病变以预防癌症形成。使用仓鼠口腔化学致癌模型,我们评估了 NV1066 感染癌前病变和癌病变的能力。 NV1066持续感染发育不良细胞、原位癌和鳞状细胞癌。与未接受病毒治疗的动物相比,接受粘膜内注射 NV1066 7 周的动物表现出明显更少(3 倍)和更小(4 倍)的病变。结果表明,传染性可能依赖于单纯疱疹病毒 1 受体 nectin-1。这项研究表明,NV1066不仅可以治疗口腔鳞状细胞癌,还可以感染和治疗癌前病变,从而延缓癌症进展。总的来说,我们的研究显示了溶瘤病毒 NV1066 作为癌症预防工具的潜力。

更新日期:2019-12-06
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