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, HSV tk) 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 (HSV tk/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 HSV tk/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.