title: Lister strain vaccinia virus with thymidine kinase gene deletion is a tractable platform for development of a new generation of oncolytic virus.
abstract: 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.
authors: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
authors: J
authors: J
authors: Hughes
authors: Sino-British Research Centre for Molecular Oncology, Zhengzhou University, Zhengzhou, China.
authors: P
authors: P
authors: Wang
authors: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
authors: G
authors: G
authors: Alusi
authors: Sino-British Research Centre for Molecular Oncology, Zhengzhou University, Zhengzhou, China.
authors: H
authors: H
authors: Shi
authors: Sino-British Research Centre for Molecular Oncology, Zhengzhou University, Zhengzhou, China.
authors: Y
authors: Y
authors: Chu
authors: Sino-British Research Centre for Molecular Oncology, Zhengzhou University, Zhengzhou, China.
authors: J
authors: J
authors: Wang
authors: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
authors: V
authors: V
authors: Bhakta
authors: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
authors: I
authors: 0000000293877586
authors: I
authors: McNeish
authors: 1] Department of Surgery, University of Toronto, Toronto, ON, Canada [2] Division of Experimental Therapeutics, Toronto-General Research Institute, Toronto, ON, Canada.
authors: A
authors: A
authors: McCart
authors: 1] Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK [2] Sino-British Research Centre for Molecular Oncology, Zhengzhou University, Zhengzhou, China.
authors: N R
authors: NR
authors: Lemoine
authors: 1] Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK [2] Sino-British Research Centre for Molecular Oncology, Zhengzhou University, Zhengzhou, China.
authors: Y
authors: 0000000323676313
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D017353:Gene Deletion; D015316:Genetic Therapy; D006801:Humans; D007668:Kidney / Q000166:cytology; D051379:Mice; D009154:Mutation; D009369:Neoplasms / Q000628:therapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D012900:Smallpox Vaccine / Q000235:genetics / Q000627:therapeutic use; D013937:Thymidine Kinase / Q000235:genetics*; D014616:Vaccinia virus / Q000235:genetics*; D014779:Virus Replication
chemical_list: D012900:Smallpox Vaccine; D013937:Thymidine Kinase