Recombinant Interleukin-2 Enhanced the Antitumor Effect of ADV/RSV-HSV-tk/ACV Therapy in a Murine Bladder Cancer Model

Abstract

Background: Previous studies demonstrated the antitumor effects of IL-2 and ADV/RSV-HSV-tk in bladder tumor models. In our study, we employed the intramuscular injection of recombinant IL-2 combined with ADV/RSV-HSV-tk gene therapy in the MBT-2 murine bladder tumor model. Materials and Methods: In the in vitro study, after adenoviral gene transduction efficiency had been assessed, the cytotoxicity of ADV/RSV-HSV-tk/ACV was examined. In the in vivo study, ADV/RSV-HSV-tk was injected into MBT-2 subcutaneous tumors, ACV was injected intraperitoneally daily for 13 days and recombinant IL-2 was injected intramuscularly daily for 10 days. Results: The X-gal staining of MBT-2 cells infected with 125 multiplicity of injection (MOI) indicated >20% adenoviral gene transduction efficiency. The cell growth of MBT-2 infected with 125 MOI was significantly inhibited by 40 μM of ACV. In the in vivo study, the combination therapy significantly inhibited tumor growth in the MBT-2 tumor model. Conclusion: The systemic administration of recombinant IL-2 in combination with HSV-tk gene therapy exhibited an enhanced antitumor effect.