Transrectal gene therapy of the prostate in the canine model.
Direct transrectal delivery of therapeutic genes utilizing adenoviral vectors for advanced prostate cancer may offer effective treatment at the molecular level. Large animal models to assess feasibility and the intraprostatic and systemic dissemination patterns of these vectors have not been reported. For these studies, a replication-deficient (E1(-)/E3(-)) recombinant adenovirus (AdRSVlacZ) expressing bacterial beta-galactosidase (beta-gal) was delivered under transrectal ultrasound guidance. Two prostate biopsies, followed by concurrent injection of 4.8 x 10(9) pfu of the adenoviral vector divided into either 1 or 2 mL of diluent, were performed (n=4). Swabs of the rectum, sputum, and urine were collected and after 72 hours, the animals were sacrificed. Specimens were assayed for the presence of virus and beta-gal activity. Rectal swabs were transiently positive, whereas urine and sputum samples showed no detectable vector throughout the experiment. Beta-gal activity was observed at the prostate injection sites with detectable activity noted up to 7.5 mm away from the injection site. Systemic dissemination was observed regardless of the injected volume. In conclusion, transrectal prostate biopsy with concurrent prostate injection is a feasible method to deliver therapeutic adenoviral vectors for the treatment of prostate cancer; however, systemic distribution and temporary rectal shedding of virus should be anticipated.
Weld
Kyle J
KJ
Urologic Research Laboratories, University of Tennessee, Memphis, Tennessee 38163, USA.
Mayher
Brant E
BE
Allay
James A
JA
Cockroft
Jody L
JL
Reed
Christopher P
CP
Randolph
Mildred M
MM
Lu
Yi
Y
Steiner
Mitchell S
MS
Gingrich
Jeffrey R
JR
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D004247:DNA / Q000378:metabolism; D017931:DNA Primers; D004285:Dogs; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D008297:Male; D008954:Models, Biological; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000628:therapy; D012007:Rectum / Q000378:metabolism; D013183:Sputum / Q000378:metabolism; D014018:Tissue Distribution; D001616:beta-Galactosidase / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine
D017931:DNA Primers; D004247:DNA; D001616:beta-Galactosidase