SECRETED TYPE OF MODIFIED INTERLEUKIN-18 GENE TRANSDUCED INTO MOUSE RENAL CELL CARCINOMA CELLS INDUCES SYSTEMIC TUMOR IMMUNITY
2001; Lippincott Williams & Wilkins; Volume: 165; Issue: 6 Part 1 Linguagem: Inglês
10.1016/s0022-5347(05)66290-8
ISSN1527-3792
AutoresShoji Hara, Hiroshi Nagai, Hideaki Miyake, Kazuki Yamanaka, Soichi Arakawa, Masamitsu Ichihashi, Sadao Kamidono, Isao Hara,
Tópico(s)T-cell and B-cell Immunology
ResumoNo AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Jun 2001SECRETED TYPE OF MODIFIED INTERLEUKIN-18 GENE TRANSDUCED INTO MOUSE RENAL CELL CARCINOMA CELLS INDUCES SYSTEMIC TUMOR IMMUNITY SHOJI HARA, HIROSHI NAGAI, HIDEAKI MIYAKE, KAZUKI YAMANAKA, SOICHI ARAKAWA, MASAMITSU ICHIHASHI, SADAO KAMIDONO, and ISAO HARA SHOJI HARASHOJI HARA More articles by this author , HIROSHI NAGAIHIROSHI NAGAI More articles by this author , HIDEAKI MIYAKEHIDEAKI MIYAKE More articles by this author , KAZUKI YAMANAKAKAZUKI YAMANAKA More articles by this author , SOICHI ARAKAWASOICHI ARAKAWA More articles by this author , MASAMITSU ICHIHASHIMASAMITSU ICHIHASHI More articles by this author , SADAO KAMIDONOSADAO KAMIDONO More articles by this author , and ISAO HARAISAO HARA More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)66290-8AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Interleukin (IL)-18 is a novel cytokine that has been identified as a strong interferon-γ inducer. IL-18 has bioactivity similar to that of IL-12 and demonstrates antitumor effects. Since IL-18 does not have a signal sequence, we constructed the gene, consisting of the signal sequences of interferon-β and mature IL-18 complementary (c) DNA. The modified gene was subsequently transduced into a mouse renal cell carcinoma cell line to induce IL-18 secretion from tumor cells to establish whether this IL-18 secreting tumor cell line may induce systemic tumor immunity. Materials and Methods: Modified IL-18 cDNA consisting of the signal sequences of interferon-β and mature type of IL-18 cDNA was constructed by the overlap extension method. The modified and original IL-18 cDNA was transduced into the RenCa mouse renal cell carcinoma cell line. Expression of IL-18 messenger RNA and concentration of IL-18 in the culture supernatant were determined. Direct antitumor and tumor vaccine effects were investigated in syngeneic Balb/c mice. To determine the mechanism of the antitumor effect immunodeficient mice were challenged with IL-18 secreting RenCa cells. Results: Although the modified and original IL-18 genes transduced RenCa showed almost the same level of IL-18 messenger RNA expression, only RenCa cells transduced with modified IL-18 gene secreted IL-18 into the culture supernatant and were completely rejected when transplanted into syngeneic mice. T lymphocytes were involved in this antitumor effect. Moreover, the modified IL-18 transduced RenCa induced tumor vaccine effect against parental RenCa cells injected at a distant site. Conclusions: Immune gene therapy using modified IL-18 cDNA appears to be effective and IL-18 secreting cancer cells may be a candidate for tumor vaccine therapy. References 1 : Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature1995; 378: 88. Google Scholar 2 : In vivo antitumor effects of murine interferon-g-inducing factor/interleukin-18 in mice bearing syngeneic Meth A sarcoma ascites. Cancer Immunol Immunother1997; 43: 361. Google Scholar 3 : Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med1993; 178: 1223. Google Scholar 4 : Effectiveness of cancer vaccine therapy using cells transduced with the interleukin-12 gene combined with systemic interleukin-18 administration. Cancer Gene Ther2000; 7: 83. Google Scholar 5 : Activation of interferon-gamma inducing factor mediated by interleukin-1 beta converting enzyme. Science1997; 275: 206. Google Scholar 6 : Efficient cell surface expression of class II MHC molecules in the absence of associated invariant chain. J Exp Med1986; 164: 1478. Google Scholar 7 : Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet1982; 1: 327. Google Scholar 8 : Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now?. Immunol Today1994; 15: 48. Google Scholar 9 : Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA1993; 90: 3539. Google Scholar 10 : Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med1989; 170: 827. Google Scholar 11 : Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. Blood1994; 84: 4008. Google Scholar 12 : Interferon-gamma inducing factor gene transfection into Lewis lung carcinoma cells reduces tumorigenicity in vivo. Jpn J Cancer Res1997; 88: 501. Google Scholar 13 : Interferon-g-inducing factor elicits antitumor immunity in association with interferon-g production. J Immunother1998; 21: 48. Google Scholar 14 : Neuroblastoma cells expressing mature IL-18, but not pro IL-18, induces a strong and immediate antitumor immune response. J Immunother1999; 22: 324. Google Scholar 15 : Rejection of mouse renal cell carcinoma elicited by local secretion of interleukin-2. Jpn J Cancer Res1996; 87: 724. Google Scholar 16 : Interferon-g-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-g production. Eur J Immunol1996; 26: 1647. Google Scholar 17 : IFN-g-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J Immunol1997; 158: 1541. Google Scholar From the Departments of Urology and Dermatology, Kobe University School of Medicine, Kobe, Japan© 2001 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byFurukawa J, Hara I, Nagai H, Yao A, Oniki S and Fujisawa M (2018) Interleukin-21 Gene Transfection Into Mouse Bladder Cancer Cells Results in Tumor Rejection Through the Cytotoxic T Lymphocyte ResponseJournal of Urology, VOL. 176, NO. 3, (1198-1203), Online publication date: 1-Sep-2006. Volume 165Issue 6 Part 1June 2001Page: 2039-2043 Advertisement Copyright & Permissions© 2001 by American Urological Association, Inc.Keywordsinterleukin-18gene therapykidneycarcinoma, renal cellMetricsAuthor Information SHOJI HARA More articles by this author HIROSHI NAGAI More articles by this author HIDEAKI MIYAKE More articles by this author KAZUKI YAMANAKA More articles by this author SOICHI ARAKAWA More articles by this author MASAMITSU ICHIHASHI More articles by this author SADAO KAMIDONO More articles by this author ISAO HARA More articles by this author Expand All Advertisement PDF downloadLoading ...
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