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/RSV-mIL-2) alone or in combination with HSV-tk+GCV will improve antitumorigenic response in the murine MBT-2 model. Materials and Methods. mIL-2 production and toxicity were determined in vitro using an ELISA and a cell proliferation assay. Tumor-bearing animals were randomly assigned into four treatment groups and directly injected with combinations of ADV/RSV-tk and ADV/RSV-mIL-2. In a separate experiment, the above-mentioned groups were followed by two subsequent treatments with ADV/RSV-mIL-2. Results. Transduced MBT-2 cells were able to express mIL-2 in a time and dose dependent fashion. We could not demonstrate any improvement in antitumorigenic response with mIL-2 gene therapy alone or in combination with HSV-tk-suicide gene therapy over HSV-tk suicide gene therapy alone. Conclusions. Although ADV/RSV-mIL-2 transduced MBT-2 cells were able to produce large amounts of mIL-2 in vitro, we could not demonstrate significant tumor growth inhibition by adding mIL-2 gene therapy to suicide gene therapy. The growth inhibitory effects of sequential suicide and cytokine gene therapy were transient and not superior to single dose suicide and cytokine gene therapy.