Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
Sino-British Research Centre for Molecular Oncology, Zhengzhou University, Zhengzhou, China.
Gene Ther. 2015 Jun;22(6):476-84. doi: 10.1038/gt.2015.13. Epub 2015 Apr 16.
Vaccinia virus (VV) has many attractive characteristics as a potential cancer therapeutic. There are several strains of VV. The nonvaccine strain Western Reserve VV with deletion of both the thymidine kinase and the viral growth factor genes (known as WRDD) has been reported as the most potent tumor-targeted oncolytic VV. Other strains, such as the European vaccine Lister strain, are largely untested. This study evaluated the antitumor potency and biodistribution of different VV strains using in vitro and in vivo models of cancer. Lister strain virus with thymidine kinase gene deletion (VVΔTK) demonstrated superior antitumor potency and cancer-selective replication in vitro and in vivo, compared with WRDD, especially in human cancer cell lines and immune-competent hosts. Further investigation of functional mechanisms revealed that Lister VVΔTK presented favorable viral biodistribution within the tumors, with lower levels of proinflammatory cytokines compared with WRDD, suggesting that Lister strain may induce a diminished host inflammatory response. This study indicates that the Lister strain VVΔTK may be a particularly promising VV strain for the development of the next generation of tumor-targeted oncolytic therapeutics.
牛痘病毒（VV）具有许多作为潜在癌症治疗方法的吸引人的特性。有几种 VV 株。已报道缺失胸苷激酶和病毒生长因子基因的非疫苗株西部储备 VV（称为 WRDD）是最有效的肿瘤靶向溶瘤 VV。其他株，如欧洲疫苗李斯特株，基本上未经测试。本研究使用癌症的体外和体内模型评估了不同 VV 株的抗肿瘤效力和生物分布。与 WRDD 相比，缺失胸苷激酶基因的李斯特株病毒（VVΔTK）在体外和体内显示出优异的抗肿瘤效力和癌症选择性复制能力，尤其是在人癌细胞系和免疫功能正常的宿主中。对功能机制的进一步研究表明，李斯特 VVΔTK 在肿瘤内呈现出有利的病毒生物分布，与 WRDD 相比，促炎细胞因子水平较低，这表明李斯特株可能引起宿主炎症反应减弱。本研究表明，李斯特株 VVΔTK 可能是开发下一代肿瘤靶向溶瘤治疗药物的特别有前途的 VV 株。
