RT Journal Article SR Electronic T1 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 JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2861 OP 2867 VO 24 IS 5A A1 CHRISTIAN LIEBAU A1 CHRISTIAN ROESEL A1 SEBASTIAN SCHMIDT A1 CHRISTIAAN KARREMAN A1 JOHANNES BERND PRISACK A1 HANS BOJAR A1 HARRY MERK A1 NEUMANN WOLFRAM A1 AXEL W.A. BALTZER YR 2004 UL http://ar.iiarjournals.org/content/24/5A/2861.abstract AB Background: 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. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved