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Viral Vector Delivery in Solid-State Vehicles: Gene Expression in a Murine Prostate Cancer Model

Viral Vector Delivery in Solid-State Vehicles: Gene Expression in a Murine Prostate Cancer Model AbstractBACKGROUND: Although there are increasingly more clinical trials involving genetherapy, efficient gene transfer remains a major hurdle to success. To enhance the efficiency ofdelivery of viral vectors in gene therapy protocols, we evaluated the effect of various matrices toact as a vehicle for recombinant virus during intratumoral injection. METHODS: Theability of several vehicles (catgut spacer, polyglycolic acid, chromic catgut, and gelatin spongematrix) to deliver the canarypox virus ALVAC to the cells of the murine prostate cancer cell lineRM-1 was studied in vitro and in vivo. ALVAC recombinants encoding themurine 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 intratumoralinoculation. Confirmatory experiments were conducted by use of another mouse prostate cancercell line, RM-11, and a mouse bladder cancer cell line, MB-49. All statistical tests weretwo-sided. RESULTS: The gelatin sponge matrix proved to be the most effectivesolid-state vehicle for delivering viral vectors to cells in culture. In addition, this matrixstatistically significantly enhanced expression of ALVAC-delivered reporter genes in tumormodels when compared with fluid-phase delivery of virus (P = .037 for theRM-1 model and P = .03 for the MB-49 model). Statistically significant growthinhibition of established tumors was observed when a combination of the three recombinantALVAC viruses expressing IL-2, IL-12, and TNF-α was delivered with the matrix incomparison with 1) fluid-phase intratumoral injection of the ALVAC recombinants, 2) notreatment, or 3) treatment with parental ALVAC (all P<.05). CONCLUSIONS:Viral vector delivery in a solid-state vehicle resulted in improved recombinant gene expression in vivo and translated to greater inhibition of tumor growth in an immunotherapyprotocol for heterotopic tumor nodules. The efficient delivery of reporter genes described hereinmay prove useful in many solid tumor gene therapy protocols. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of the National Cancer Institute Oxford University Press

Viral Vector Delivery in Solid-State Vehicles: Gene Expression in a Murine Prostate Cancer Model

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References (40)

Publisher
Oxford University Press
Copyright
Oxford University Press
ISSN
0027-8874
eISSN
1460-2105
DOI
10.1093/jnci/92.5.403
Publisher site
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Abstract

AbstractBACKGROUND: Although there are increasingly more clinical trials involving genetherapy, efficient gene transfer remains a major hurdle to success. To enhance the efficiency ofdelivery of viral vectors in gene therapy protocols, we evaluated the effect of various matrices toact as a vehicle for recombinant virus during intratumoral injection. METHODS: Theability of several vehicles (catgut spacer, polyglycolic acid, chromic catgut, and gelatin spongematrix) to deliver the canarypox virus ALVAC to the cells of the murine prostate cancer cell lineRM-1 was studied in vitro and in vivo. ALVAC recombinants encoding themurine 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 intratumoralinoculation. Confirmatory experiments were conducted by use of another mouse prostate cancercell line, RM-11, and a mouse bladder cancer cell line, MB-49. All statistical tests weretwo-sided. RESULTS: The gelatin sponge matrix proved to be the most effectivesolid-state vehicle for delivering viral vectors to cells in culture. In addition, this matrixstatistically significantly enhanced expression of ALVAC-delivered reporter genes in tumormodels when compared with fluid-phase delivery of virus (P = .037 for theRM-1 model and P = .03 for the MB-49 model). Statistically significant growthinhibition of established tumors was observed when a combination of the three recombinantALVAC viruses expressing IL-2, IL-12, and TNF-α was delivered with the matrix incomparison with 1) fluid-phase intratumoral injection of the ALVAC recombinants, 2) notreatment, or 3) treatment with parental ALVAC (all P<.05). CONCLUSIONS:Viral vector delivery in a solid-state vehicle resulted in improved recombinant gene expression in vivo and translated to greater inhibition of tumor growth in an immunotherapyprotocol for heterotopic tumor nodules. The efficient delivery of reporter genes described hereinmay prove useful in many solid tumor gene therapy protocols.

Journal

Journal of the National Cancer Institute – Oxford University Press

Published: Mar 1, 2000

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