Immunotherapy by gene transfer with plasmids encoding IL-12/IL-18 is superior to IL-23/IL-18 gene transfer in a rat osteosarcoma model

Abstract

Osteosarcomas are primary malignant tumors of bone or soft parts arising from bone-forming mesenchymal cells. Despite dramatic therapeutic advances, namely neo-adjuvant and adjuvant chemotherapy, progress is at a plateau. Cytokine-mediated gene therapy might represent a further advance in the therapy of the osteosarcoma. Materials and Methods: We transfected UMR 108 osteosarcoma cells with different plasmids encoding IL-12, IL-23, proIL-18 and ICE (Interleukin-converting enzyme). IFN-γ induction, which is known to induce antitumor effects mediated by the immune system, and cytotoxic effects of various cytokine combination were investigated. Results: Our results show that local secretion of IL-12 by UMR 108 cells led to an induction of cytotoxic effects mediated by mononuclear cells, which were enhanced by additional administration of recombinant IL-18. In contrast to IL-18, IL-23 showed a moderate increase of IFN-γ induction when transfected alone and could only slightly increase the IFN-γ induction mediated by IL-12. IL-18 enhanced IFN-γ induction when applied alone and was able to increase the IFN-γ production that was induced by IL-12. Conclusion: IL-23 seems to be a less effective immuno-therapeutic for adjuvant treatment of osteosarcomas than IL-12 and IL-18, when taking only IFN-γ induction into consideration.