Intratumoral IL-12 gene transfer improves the therapeutic efficacy of IL-12 but not IL-19.
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 Mc12 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 IFN gamma 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.
Sobota
V
V
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague.
Bubeník
J
J
Símová
J
J
Jandlová
T
T
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018664:Interleukin-12 / Q000627:therapeutic use*; D020382:Interleukin-18 / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000627:therapeutic use; D014162:Transfection; D014407:Tumor Cells, Cultured
D020382:Interleukin-18; D007376:Interleukin-2; D011994:Recombinant Proteins; D018664:Interleukin-12