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Adenovirus-mediated combination suicide and cytokine gene therapy for bladder cancer
C T Freund1, M A Sutton, T Dang
1Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
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.
Insights
Murine interleukin-2 (mIL-2) gene therapy, alone or with HSV-tk suicide gene therapy, did not improve antitumorigenic response in the MBT-2 model. The combination therapy showed only transient tumor growth inhibition, not superior to single-dose treatments.
Area of Science:
- Oncology
- Gene Therapy
- Immunotherapy
Background:
- Adenovirus-mediated transfer of murine interleukin-2 (ADV/RSV-mIL-2) was investigated for its potential to enhance antitumorigenic responses.
- The study also evaluated the combination of mIL-2 gene therapy with herpes simplex virus-thymidine kinase (HSV-tk) suicide gene therapy and ganciclovir (GCV).
Purpose of the Study:
- To test the hypothesis that mIL-2 gene therapy, alone or combined with HSV-tk/GCV, improves antitumorigenic response in the murine MBT-2 model.
- To assess the efficacy and toxicity of mIL-2 gene therapy in combination with suicide gene therapy.
Main Methods:
- Murine IL-2 (mIL-2) production and toxicity were assessed in vitro using ELISA and cell proliferation assays.
- Tumor-bearing mice were treated with ADV/RSV-tk and ADV/RSV-mIL-2, with some groups receiving sequential treatments.
Main Results:
- Transduced MBT-2 cells successfully expressed mIL-2 in vitro in a time- and dose-dependent manner.
- No significant improvement in antitumorigenic response was observed with mIL-2 gene therapy alone or in combination with HSV-tk suicide gene therapy compared to HSV-tk therapy alone.
Conclusions:
- Despite in vitro mIL-2 production, ADV/RSV-mIL-2 gene therapy did not significantly inhibit tumor growth when added to suicide gene therapy.
- Sequential suicide and cytokine gene therapy demonstrated transient growth inhibitory effects that were not superior to single-dose treatments.