Viral vector delivery in solid-state vehicles: Gene expression in a murine prostate cancer model

D. Robert Siemens, James (Christopher) Austin, Sean P. Hedican, James Tartaglia, Timothy L. Ratliff

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Background: Although there are increasingly more clinical trials involving gene therapy, efficient gene transfer remains a major hurdle to success. To enhance the efficiency of delivery of viral vectors in gene therapy protocols, we evaluated the effect of various matrices to act as a vehicle for recombinant virus during intratumoral injection. Methods: The ability of several vehicles (catgut spacer, polyglycolic acid, chromic catgut, and gelatin sponge matrix) to deliver the canarypox virus ALVAC to the cells of the murine prostate cancer cell line RM-1 was studied in vitro and in vivo. ALVAC recombinants encoding the murine cytokines interleukin 2 (IL-2), interleukin 12 (IL-12), and tumor necrosis factor-α (TNF-α) were used to assess enhancement of antitumor activity after intratumoral inoculation. Confirmatory experiments were conducted by use of another mouse prostate cancer cell line, RM-11, and a mouse bladder cancer cell line, MB- 49. All statistical tests were two-sided. Results: The gelatin sponge matrix proved to be the most effective solid-state vehicle for delivering viral vectors to cells in culture. In addition, this matrix statistically significantly enhanced expression of ALVAC-delivered reporter genes in tumor models when compared with fluid-phase delivery of virus (P = .037 for the RM- 1 model and P = .03 for the MB-49 model). Statistically significant growth inhibition of established tumors was observed when a combination of the three recombinant ALVAC viruses expressing IL-2, IL-12, and TNF-α was delivered with the matrix in comparison with 1) fluid-phase intratumoral injection of the ALVAC recombinants, 2) no treatment, or 3) treatment with parental ALVAC (all P

Original languageEnglish (US)
Pages (from-to)403-412
Number of pages10
JournalJournal of the National Cancer Institute
Volume92
Issue number5
StatePublished - Mar 1 2000
Externally publishedYes

Fingerprint

Catgut
Prostatic Neoplasms
Porifera
Gelatin
Interleukin-12
Viruses
Gene Expression
Cell Line
Genetic Therapy
Interleukin-2
Canarypox virus
Tumor Necrosis Factor-alpha
Polyglycolic Acid
Injections
Reporter Genes
Urinary Bladder Neoplasms
Neoplasms
Cell Culture Techniques
Clinical Trials
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Viral vector delivery in solid-state vehicles : Gene expression in a murine prostate cancer model. / Siemens, D. Robert; Austin, James (Christopher); Hedican, Sean P.; Tartaglia, James; Ratliff, Timothy L.

In: Journal of the National Cancer Institute, Vol. 92, No. 5, 01.03.2000, p. 403-412.

Research output: Contribution to journalArticle

Siemens, D. Robert ; Austin, James (Christopher) ; Hedican, Sean P. ; Tartaglia, James ; Ratliff, Timothy L. / Viral vector delivery in solid-state vehicles : Gene expression in a murine prostate cancer model. In: Journal of the National Cancer Institute. 2000 ; Vol. 92, No. 5. pp. 403-412.
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