Fundamental Study of Gene Therapy for Renal Cell Carcinoma Using IL-12

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Interleukin-12 (IL-12) is expected a cytokine which can induce a potent antitumor effect. To determine the possibility of IL-12 for gene therapy of renal cell carcinoma, we prepared genetically engineered murine renal cell carcinoma to secrete IL-12 using MFG retroviral vector. Renca IL-12 can secrete 146.7ng of bioactive IL-12/ml/1x10^6cell/48 hr. In vivo tumorigenecity of Renca IL-12 reduced significantly compared with Renca wild and lac Z,whereas in vitro growth and surface antigen, such as MHC class I,class II,or B7-1, of each cells did not alter. These results suggested that antitumor immune response induced by high concentration of IL-12 in local site might be responsible for loss of tumorigenecity of Renca IL-12. Renca IL-12 also inhibited the growth of Renca wild at a distant site. Furthermore, some mice rejected inoculated Renca IL-12 were determined to be immune to a rechallenge of Renca wild. We believe that these results support the feasibility of IL-12 gene therapy for the treatment of renal cell carcinoma.