Fol. Biol. 2000, 46, 191-193
Intratumoral IL-2 Gene Transfer Improves the Therapeutic Efficacy of IL-12 but Not IL-18
We have compared the therapeutic activity of IL-12 and IL-18 in mice carrying IL-2 gene-transduced syngeneic sarcoma Mc12. The IL-2 gene-transduced sarcoma has previously been utilized as an irradiated, genetically modified tumour vaccine. Murine recombinant IL-12 was capable of suppressing growth of the IL-2 gene-modified sarcoma Mc12 in syngeneic mice more efficiently than growth of the parental Mc12 sarcoma. In contrast, murine recombinant IL-18 could neither inhibit growth of the parental Mcl2 sarcoma, nor suppress growth of its IL-2 gene-modified transfectant. These results suggest that although both of these cytokines are functionally related and participate in the induction of IFNγ production as well as in cell-mediated immune cytotoxicity, in the murine sarcoma system only IL-12 is therapeutically active 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 adjuvant in IL-2 gene therapy with irradiated, genetically modified tumour vaccines.
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Funding
This work was supported by grants Nos. NC 5526-3 and NC 4501-3 from the Grant Agency of the Ministry of Health of the Czech Republic, Nos. 301/00/P021, 312/98/0826, 312/99/0542, and 301/00/0114 from the Grant Agency of the Czech Republic, No. A7052002 from the Grant Agency of the Academy of Sciences of the Czech Republic, and by Czech Terry Fox Foundation.
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