| Autor: |
Sonoda-Fukuda E; Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Nishinomiya 663-8501, Japan., Takeuchi Y; Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Nishinomiya 663-8501, Japan.; Departments of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda 669-1330, Japan., Ogawa N; Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Nishinomiya 663-8501, Japan.; Departments of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda 669-1330, Japan., Noguchi S; Laboratory of Veterinary Radiology, Graduate School of Veterinary Science, Osaka Metropolitan University, Izumisano 598-8531, Japan., Takarada T; Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Nishinomiya 663-8501, Japan.; Laboratory of Functional Molecular Chemistry, Kobe Pharmaceutical University, Kobe 658-8558, Japan., Kasahara N; Departments of Neurological Surgery and Radiation Oncology, University of California, San Francisco, CA 94143, USA., Kubo S; Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Nishinomiya 663-8501, Japan. |
| Abstrakt: |
Cancer in dogs has increased in recent years and is a leading cause of death. We have developed a retroviral replicating vector (RRV) that specifically targets cancer cells for infection and replication. RRV carrying a suicide gene induced synchronized killing of cancer cells when administered with a prodrug after infection. In this study, we evaluated two distinct RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV) in canine tumor models both in vitro and in vivo. Despite low infection rates in normal canine cells, both RRVs efficiently infected and replicated within all the canine tumor cells tested. The efficient intratumoral spread of the RRVs after their intratumoral injection was also demonstrated in nude mouse models of subcutaneous canine tumor xenografts. When both RRVs encoded a yeast cytosine deaminase suicide gene, which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil, they caused tumor-cell-specific 5-FC-induced killing of the canine tumor cells in vitro. Furthermore, in the AZACF- and AZACH-cell subcutaneous tumor xenograft models, both RRVs exerted significant antitumor effects. These results suggest that RRV-mediated suicide gene therapy is a novel therapeutic approach to canine cancers. |
