Abstract
It is critical to develop new therapies to improve anti-tumor activity and decrease the toxicity to normal host cells. Gene therapy is a novel therapeutic approach with high potential to cure immune-resistant tumor cells. In this study, we used prostate cancer cell line, TRAMP-C1, as a research model and combined gene therapy using suicide gene system HSV1-tk/GCV and immunotherapy using murine interleukin-3 (mIL-3) to evaluate the anti-tumor effect. First, we constructed two transfected cell lines, TRAMP-C1/TK and TRAMP-C1/IL3-TK, by liposomal DNA delivery system. These transfected cell lines have high sensitivity to the cytotoxic effect of ganciclovir (GCV). The transfected tumor cells were subscutaneously inoculated into the right flank of C57BL/6J mice to establish a tumor model. The results show that the combination of HSV1-tk/GCV and mIL-3 treatment significantly delays the tumor growth rate. The treatment with HSV1-tk/GCV alone causes transient tumor growth delay in comparison to combined therapy. In immune functional assay, we didn’t observe expected enhancement of cytotoxic T lymphocyte response. However, the ability of CD4 T cells secreting IFN-γ is improved in combined treatment with HSV1-tk/GCV and mIL-3. These results indicate that this combined system can recover down-regulated immunity and enhance anti-tumor activity. In summary, we have already established a combined gene therapy system, which relies on the cytotoxicity of GCV treatment and immune responses stimulated by mIL-3. This system can active CD4 T cells to secret IFN-γand delay the tumor growth rate.