Intratumoral IL-2 gene transfer improves the therapeutic efficacy of IL-12but not IL-18

We have compared the therapeutic activity of IL-12 and IL-18 in mice carryi ng IL-2 gene-transduced syngeneic sarcoma Mc12. The IL-2 gene-transduced sa rcoma has previously been utilized as an irradiated, genetically modified t umour vaccine. Murine recombinant IL-12 was capable of suppressing growth o f the IL-2 gene-modified sarcoma Mc12 in syngeneic mice more efficiently th an growth of the parental Mc12 sarcoma. In contrast, murine recombinant IL- 18 could neither inhibit growth of the parental Mc12 sarcoma, nor suppress growth of its IL-2 gene-modified transfectant. These results suggest that a lthough both of these cytokines are functionally related and participate in the induction of IFN gamma production as well as in cell-mediated immune c ytotoxicity, in the murine sarcoma system only IL-12 is therapeutically act ive and exerts its therapeutic effect in concert with the IL-2 gene. Thus, intratumoral IL-2 gene transfer improves the therapeutic efficacy of IL-12; administration of recombinant IL-12 should therefore be considered as adju vant in IL-2 gene therapy with irradiated, genetically modified tumour vacc ines.