Intravesical interleukin-12 Gene Therapy in an Orthotopic Bladder Cancer Model

Urology. 2005 Aug;66(2):461-6. doi: 10.1016/j.urology.2005.03.052.

Abstract

Objectives: To evaluate the antitumor effect of intravesical cationic liposome-mediated interleukin-12 (IL-12) gene delivery in an orthotopic murine bladder cancer model, and to investigate the immunologic memory against tumors between IL-12 gene therapy and bacille Calmette-Guérin (BCG) therapy.

Methods: Orthotopic murine bladder tumors were established by implanting 5 x 10(5) MBT-2 cells into the bladder of syngeneic female C3H mice. Intravesical IL-12 gene therapy was evaluated at varying doses: 0 microg (control) and 3, 5, and 10 microg (n = 8 for each group). Intravesical treatments were performed every 3 days and repeated six times beginning 5 days after tumor implantation. To compare the long-term, tumor-specific immunity between IL-12-treated mice (n = 18) and BCG-treated mice (n = 20), the animals surviving at day 60 and 10 new control mice were rechallenged with MBT-2 cells and received no additional treatment. On day 120, all surviving mice were killed and underwent necropsy.

Results: In the IL-12 groups at doses of 0, 3, 5, and 10 microg, 0, 2, 3, and 3 mice survived, respectively. Mice in the 5-microg and 10-microg IL-12 groups survived significantly longer than did the control group. All mice cured by IL-12 treatment successfully rejected the rechallenge with MBT-2 cells; however, mice cured by BCG and the new control mice died of the rechallenged bladder tumors.

Conclusions: Intravesical IL-12 gene therapy, which induced long-lasting tumor-specific immunologic memory compared with BCG therapy, improved survival in an orthotopic bladder cancer model.

MeSH terms

  • Animals
  • BCG Vaccine / therapeutic use*
  • Female
  • Genetic Therapy*
  • Interleukin-12 / genetics*
  • Interleukin-12 / therapeutic use*
  • Liposomes
  • Mice
  • Neoplasm Transplantation
  • Urinary Bladder Neoplasms / drug therapy*

Substances

  • BCG Vaccine
  • Liposomes
  • Interleukin-12