Immunotherapy of bladder cancer

Abstract

In this study, we evaluated the feasibility and efficacy of cytokine gene therapy in a murine orthotopic model of TCC. Orthotopic tumor was established with 1 x 105 MB49 cells in C57BL/6 mice using a modified electro-cautery technique. In situ gene transfer to bladder tumors was accomplished via intravesical instillation of plasmid DNA/DOTAP/methyl-beta-cyclodextrin solubilized cholesterol after a single 2h transfection. Moreover, we developed a new model by modifying the bladder cancer cell line MB49 to secrete PSA. PSA could be detected in both serum and urine and its changes reflect the tumor burden in vivo. Therefore, tumor growth and response to treatment could be monitored over time. Tumor bearing mice were treated with plasmid DNA encoding cytokines complexed with liposome by intravesical instillation twice a week for 3 weeks. The results demonstrated that liposome-mediated cytokine gene therapy provides an effective therapy by significantly inhibiting tumor growth and improving survival.