ANTITUMOR VACCINE EFFECT OF IRRADIATED MURINE NEUROBLASTOMA-CELLS PRODUCING INTERLEUKIN-2 OR GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR

We have examined vaccination effects of cytokine-producing murine neur oblastoma cells (C1300). C1300 cells retrovirally transduced with inte rleukin-2 (IL-2) or granulocyte macrophage-colony stimulation factor ( GMCSF) gene were established. Their in vitro proliferation rates and t he class I expression of major histocompatibility complex were not dif ferent from those of wild-type cells. Five-Gy irradiation of the respe ctive cytokine producers slightly reduced the in vitro cell growth but treatment with 15 Gy significantly impaired the proliferation. In con trast, the secretion of both cytokines from the respective transduced cells was retained compared with the cell growth. We immunized syngene ic mice with irradiated wild-type cells as a control or cytokine-produ cing cells and challenged the mice with unirradiated wild-type cells. The control mice developed tumors of the challenged wild-type cells, o n the contrary, the mice which had received irradiated IL-2 or GM-CSF producers did not. Thus, IL-2 or GM-CSF-expressing syngeneic tumor cel ls can be potentially used as a tumor vaccine by inducing protective i mmunity against low immunogenic neuroblastomas in the inoculated hosts .