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Disabled infectious single cycle herpes simplex virus (DISC‐HSV) is a candidate vector system for gene delivery/expression of GM‐CSF in human prostate cancer therapy
Author(s) -
Parkinson Richard J.,
Mian Shahid,
Bishop Michael C.,
Gray Trevor,
Li Geng,
McArdle Stephanie E.B.,
Ali Selman,
Rees Robert C.
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10207
Subject(s) - herpes simplex virus , genetic enhancement , prostate cancer , vector (molecular biology) , hsl and hsv , virology , gene , medicine , alphaherpesvirinae , virus , prostate , viral vector , gene expression , cancer research , biology , herpesviridae , immunology , pathology , cancer , viral disease , recombinant dna , genetics
BACKGROUND DISC‐HSV is a replication incompetent herpes simplex virus that is a highly efficient vector for the transduction of genes in vivo and in vitro. We examine the ability of DISC‐HSV to infect human prostate cancer cell‐lines and xenograft tumor models, and induce expression of reporter and therapeutic cytokine genes. METHODS Infection was confirmed by cellular staining for the beta‐galactosidase reporter gene product, and by EM. Human GM‐CSF production following DISC‐hGMCSF infection was measured using ELISA. The metabolic activity of infected cells was determined by NADP/NADPH assay. Cell death was estimated by cell‐cycle analysis using flow cytometry with propidium iodide staining. RESULTS Infection of DU145, PC3 and LNCaP cells with DISC‐HSV was dose dependent. Cells infected with DISC‐hGM‐CSF released significant levels of hGM‐CSF for 3 days. NADP/NADPH assay suggested that infected cells continued to be metabolically active for 3 days post‐infection, which was consistent with flow cytometry findings that cell death did not occur within 7 days of infection. Tumor xenografts injected with DISC‐HSV expressed beta‐galactosidase, and intracellular viral particles were demonstrated using EM. CONCLUSIONS We have previously reported the rejection of established tumors following intra‐tumoral injection of DISC‐GMCSF. This study demonstrates the ability of DISC‐HSV to infect prostate cancer and express GMCSF at significant levels. We suggest that prostate cancer is a potential target for therapy using DISC‐HSV containing GM‐CSF. Prostate 56: 65–73, 2003. © 2003 Wiley‐Liss, Inc.