Gmcsf and Ifnα gene therapy improves the response to BCG immunotherapy in a murine model of bladder cancer.

Aim: To develop a strategy to improve response to bacillus Calmette-Gueri (BCG) using cytokine gene therapy (Gmcsf + Ifnα). Materials & methods: MB49-PSA tumor-bearing C57BL/6N mice were assigned into four groups: control; Gmcsf + Ifnα therapy; BCG therapy or combined therapy (Gmcsf + Ifnα and BCG). In schedule 1, cytokine gene therapy was delivered before BCG therapy (eight instillations). In schedule 2, cytokine gene and BCG therapy were instilled alternatively (eight instillations). Tumors were analyzed by immunohistochemistry and mRNA analysis and urinary immune cells by flow cytometry. Results: Combined therapy in schedule 2 reduced tumor growth, increased immune cell recruitment and was associated with reduced inflammation when compared with BCG therapy. Conclusion: Alternating cytokine gene delivery with BCG therapy modulates the tumor environment increasing receptivity to BCG.