Combined suicide gene and immunostimulatory gene therapy using AAV-mediated gene transfer to HPV-16 transformed mouse cell: Decrease of oncogenicity and induction of protection

  • Authors:
    • O. Janousková
    • P. Síma
    • D. Kunke
  • View Affiliations

  • Published online on: March 1, 2003     https://doi.org/10.3892/ijo.22.3.569
  • Pages: 569-577
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

To test the effects of combined transduction of a suicide gene and genes coding for various immunostimulatory factors on the oncogenicity and immunogenicity of TC-1 cells (HPV-16 transformed C57BL/6 mouse cells), several bicistronic recombinant adeno-associated viruses (rAAV) were constructed. Each of these constructs carried, and in infected cells expressed, the herpes simplex type 1 thymidine-kinase gene (HSV-TK) and the gene of one of the following immunostimulatory factors: human monocyte chemoattractant protein 1 (MCP-1), mouse B7.1 costimulatory molecule (B7.1), or mouse granulocyte-macrophage colony-stimulating factor (GM-CSF). For control purposes, an rAAV carrying the HSV-TK gene and neomycin resistance gene (neo) and an rAAV containing the lacZ gene were used. All of these constructs proved functional both in mouse TC-1 and human 293T cells. For experiments in mice, TC-1 cells were infected in vitro with the AAV recombinants at an input multiplicity of 50 particles/cell; these cells were then administered to 5-week-old mice. As from day 5, half of the animals were given ganciclovir (GCV) (2.5 mg/day) for 10 days. With a single exception, none of the mice inoculated with cells treated with rAAV expressing HSV-TK + B7.1 or HSV-TK + MCP-1 developed tumour irrespective of GCV treatment. The tumour suppressive effect was less marked in animals inoculated with TC-1 cells infected with rAAV expressing HSV-TK + GM-CSF, and among these it was somewhat more pronounced in GCV-untreated animals. A clear antitumour effect of GCV treatment was only observed in mice inoculated with TC-1 cells transduced with rAAV expressing HSV-TK but no immunostimulatory factor. Mice that remained tumour-free on day 54 were challenged with untreated TC-1 cells. The tumour resistance rates found were related not only to the immunostimulatory gene used for the transduction, but also to GCV treatment. The best protection was recorded in mice pre-inoculated with TC-1 cells transduced with either B7.1 or MCP-1-expressing rAAV and not given GCV.

Related Articles

Journal Cover

March 2003
Volume 22 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Janousková O, Síma P and Kunke D: Combined suicide gene and immunostimulatory gene therapy using AAV-mediated gene transfer to HPV-16 transformed mouse cell: Decrease of oncogenicity and induction of protection. Int J Oncol 22: 569-577, 2003
APA
Janousková, O., Síma, P., & Kunke, D. (2003). Combined suicide gene and immunostimulatory gene therapy using AAV-mediated gene transfer to HPV-16 transformed mouse cell: Decrease of oncogenicity and induction of protection. International Journal of Oncology, 22, 569-577. https://doi.org/10.3892/ijo.22.3.569
MLA
Janousková, O., Síma, P., Kunke, D."Combined suicide gene and immunostimulatory gene therapy using AAV-mediated gene transfer to HPV-16 transformed mouse cell: Decrease of oncogenicity and induction of protection". International Journal of Oncology 22.3 (2003): 569-577.
Chicago
Janousková, O., Síma, P., Kunke, D."Combined suicide gene and immunostimulatory gene therapy using AAV-mediated gene transfer to HPV-16 transformed mouse cell: Decrease of oncogenicity and induction of protection". International Journal of Oncology 22, no. 3 (2003): 569-577. https://doi.org/10.3892/ijo.22.3.569