Adenovirus-mediated combination suicide and cytokine gene therapy for bladder cancer

Background. The present study tests the hypothesis that adenovirus-mediated transfer of murine IL-2 (ADV/RSVmIL-2) alone or in combination with HSV-tk +GCV will improve antitumorigenic response in the murine MBT-2 model Materi als and Methods, mIL-2 production and toxicity were determined in vitro usi ng an ELISA and a cell proliferation assay. Tumor-bearing animals were rand omly assigned into four treatment groups and directly injected with combina tions of ADV/RSV-tk and ADV/RST-mIL-2. In a separate experiment, the above- mentioned groups were followed by two subsequent treatments with ADV/RSV-mI L-2. Results. Transduced MBT-2 cells were able to express mIL-2 in a time a nd dose dependent fashion. We could not demonstrate any improvement in anti tumorigenic response with mIL-2 gene therapy alone or in combination with H SV-tk-suicide gene therapy over HSV-tk suicide gene therapy alone. Conclusi ons. Although ADV/RSV-mIL-2 transduced MBT-2 cells were able to produce lar ge amounts of mIL-2 in vitro, we could not demonstrate significant tumor gr owth inhibition by adding mIL-2 gene therapy to suicide gene therapy. The g rowth inhibitory effects of sequential suicide and cytokine gene therapy we re transient and not superior to single dose suicide and cytokine gene ther apy.