Transrectal gene therapy of the prostate in the canine model

Kyle J. Weld, Brant E. Mayher, James A. Allay, Jody L. Cockroft, Christopher P. Reed, Mildred M. Randolph, Yi Lu, Mitchell S. Steiner, Jeffrey R. Gingrich

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 β-galactosidase (β-gal) was delivered under transrectal ultrasound guidance. Two prostate biopsies, followed by concurrent injection of 4.8 × 109 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 β-gal activity. Rectal swabs were transiently positive, whereas urine and sputum samples showed no detectable vector throughout the experiment. β-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.

Original languageEnglish (US)
Pages (from-to)189-196
Number of pages8
JournalCancer Gene Therapy
Volume9
Issue number2
DOIs
StatePublished - Jan 1 2002

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Genetic Therapy
Canidae
Prostate
Injections
Sputum
Prostatic Neoplasms
Galactosidases
Urine
Virus Shedding
Biopsy
Therapeutics
Rectum
Adenoviridae
Animal Models
Viruses
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Weld, K. J., Mayher, B. E., Allay, J. A., Cockroft, J. L., Reed, C. P., Randolph, M. M., ... Gingrich, J. R. (2002). Transrectal gene therapy of the prostate in the canine model. Cancer Gene Therapy, 9(2), 189-196. https://doi.org/10.1038/sj.cgt.7700425

Transrectal gene therapy of the prostate in the canine model. / Weld, Kyle J.; Mayher, Brant E.; Allay, James A.; Cockroft, Jody L.; Reed, Christopher P.; Randolph, Mildred M.; Lu, Yi; Steiner, Mitchell S.; Gingrich, Jeffrey R.

In: Cancer Gene Therapy, Vol. 9, No. 2, 01.01.2002, p. 189-196.

Research output: Contribution to journalArticle

Weld, KJ, Mayher, BE, Allay, JA, Cockroft, JL, Reed, CP, Randolph, MM, Lu, Y, Steiner, MS & Gingrich, JR 2002, 'Transrectal gene therapy of the prostate in the canine model', Cancer Gene Therapy, vol. 9, no. 2, pp. 189-196. https://doi.org/10.1038/sj.cgt.7700425
Weld KJ, Mayher BE, Allay JA, Cockroft JL, Reed CP, Randolph MM et al. Transrectal gene therapy of the prostate in the canine model. Cancer Gene Therapy. 2002 Jan 1;9(2):189-196. https://doi.org/10.1038/sj.cgt.7700425
Weld, Kyle J. ; Mayher, Brant E. ; Allay, James A. ; Cockroft, Jody L. ; Reed, Christopher P. ; Randolph, Mildred M. ; Lu, Yi ; Steiner, Mitchell S. ; Gingrich, Jeffrey R. / Transrectal gene therapy of the prostate in the canine model. In: Cancer Gene Therapy. 2002 ; Vol. 9, No. 2. pp. 189-196.
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