Gene Delivery for Metastatic Prostate Cancer Cells

Abstract

Abstract : We have constructed a diphtheria toxin A (DTA) gene expression vector driven by the PSAR-PSAR promoter. The prostate-specific expression of the DTA gene specifically destroyed prostate cancer cell line LNCaP in vitro. Enhanced by the bystander effect, the specific expression of the DTA gene causes significant cell death in prostate cancer cell cultures, with very low background cell eradication in control cell lines. The highly specific and efficient cytopathicity of the DTA vector will potentially be valuable for systemic treatment of patients with metastatic prostate cancer. We also constructed prostate-specific lentiviral vectors and used nude mice carrying human prostate cancer cell line LNCaP as animal model (Cancer Gene Therapy, in press). Significant tumor regression has been demonstrated in mice injected by the prostate-specific DTA vector while no pathogenic effects have been demonstrated. Our results demonstrated that vectors that are constructed by combining our prostate tissue-specific promoter and the DTA gene offer target-specific prostate cancer cell eradication in both cell culture and in vivo.