title: Oncolytic adenovirus delivering herpes simplex virus thymidine kinase suicide gene reduces the growth of human retinoblastoma in an in vivo mouse model.
abstract: Oncolytic conditionally replicating adenoviruses (CRAd) can exclusively replicate in and lyse tumor cells and are therefore promising tools in cancer therapy. In this study, we combined the oncolytic potential of a CRAd with its ability to deliver a suicide gene (herpes simplex virus thymidine kinase suicide gene, HSVtk) in order to further enhance tumor cell killing in a human retinoblastoma (RB) mouse model. We could demonstrate that CRAd driven by the human telomerase reverse transcriptase (hTERT) promoter and armed with the HSV thymidine kinase suicide gene/ganciclovir (HSVtk/GCV) could very effectively reduce growth of human RB in an orthotopic nude mouse model. These findings suggest that hTERT promoter-driven CRAd in combination with HSVtk/GCV gene therapy could be a promising new approach for the treatment of RB. In addition, we found that hTERT promoter-driven CRAd replication occurred exclusively in human RB cells but not in primary human retinal pigment epithelial cells (hRPE), indicating that application of hTERT promoter-driven CRAd for the treatment of RB would be safe.
authors.affiliation: Experimental Center, The First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Xunda
authors.initials: X
authors.lastname: Ji
authors.forename: Jufeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.forename: Fang
authors.initials: F
authors.lastname: Wei
authors.forename: Huiming
authors.initials: H
authors.lastname: Li
authors.forename: Xinjian
authors.initials: X
authors.lastname: Liu
authors.forename: Xiafang
authors.initials: X
authors.lastname: Chen
authors.forename: Chuanyuan
authors.initials: C
authors.lastname: Li
authors.forename: Yufei
authors.initials: Y
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang