Induced immunity by expression of interleukin-2 or GM-CSF gene in murine neuroblastoma cells can generate antitumor response to established tumors

We examined whether antitumor immunity could be generated by the inoculation of cytokine-producing murine neuroblastoma cells (C1300), and whether the immunity might be effective for the established tumors of wild-type (wt) cells. For that purpose, we transduced low immunogenic C1300 cells with interleukin-2 (IL-2) GM-CSF, or IL-4 genes. A loss of tumorigenicity in syngeneic mice was observed using IL-2- and GM-CSF- but not IL-4-producing C1300 cells, although their in vitro growth rates were not affected by the transduction. The syngeneic mice that had rejected IL-2 or GM-CSF producers did not develop tumors of wt cells inoculated subsequently, but formed tumors of irrelevant syngeneic mammary tumor cells. Accordingly, the inoculation of IL-2 or GM-CSF producers into immunocompetent mice generated tumor-specific acquired immunity. The induced immunity using IL-2 or GM-CSF producers was also effective in eradicating established subcutaneous tumors of wt cells and in reducing the number of preexisting metastatic foci in the liver. These data suggest a potential application of IL-2- or GM-CSF-producing syngeneic tumor cells for the treatment of low immunogenic neuroblastomas.