Potent antitumor effects mediated by local expression of the mature form of the interferon-γ inducing factor, interleukin-18 (IL-18)

A novel isoform of pro-interleukin-18 expressed in ovarian tumors is resistant to caspase-1 and -4 processing

“…The altered capability to produce biologically active forms of IL-15 or of IL-18 may perhaps confer an immune privilege to tumors during neoplastic transformation. Indeed tumor cells genetically engineered to express biologically active IL-15 (Meazza et al, 2000) or IL-18 (Osaki et al, 1999;Tatsumi et al, 2002) show a reduction in their tumorigenicity in experimental tumor models and induce immune reactions, in relationship to the induction of IFNg production (Coughlin et al, 1998;Meazza et al, 2000;Tatsumi et al, 2002). IFNg is not spontaneously secreted by ovarian tumors (Nash et al, 1998), which release several other cytokines involved in tumor progression or autocrine loops (Naylor et al, 1993;Wu et al, 1993;Hartenbach et al, 1997;Mesiano et al, 1998).…”

In vivo electroporation-mediated transfer of interleukin-12 and interleukin-18 genes induces significant antitumor effects against melanoma in mice

“…pGEG.mIL-12 contains a bicistronic expression cassette with murine IL-12 p35 and p40 genes, 18 while pGEG.mIL-18 contains murine IL-18 cDNA fused with the leader sequence of the human parathyroid hormone gene. 18 pGEG.EGFP carries the enhanced green fluorescent protein (EGFP) gene (SalINotI 0.7 kb fragment derived from pEGFP.N3 (Clontech, Palo Alto, CA, USA)). pG.luc, pG.mIL-12 and pG.mIL-18 were constructed from pGEG.luc, pGEG.mIL-12 and pGEG.mIL-18, respectively, by deleting both CAG-EBNA1 and oriP.…”

“…1 Osaki et al 18 reported a synergistic antitumor effect of IL-18 gene transduction and recombinant IL-12 administration. However, most of these earlier studies employed retrovirus, [18][19][20][21] or adenovirus vectors, 22,23 while cationic liposome was also used in some studies. 24 In the present study, IL-12 and IL-18 genes were trans-ferred into B16 solid tumors via electroporation, as a novel approach to gene therapy of cancer.…”

A Functional SNP of the Interleukin-18 Gene Is Associated with the Presence of Hepatocellular Carcinoma in Hepatitis B Virus-Infected Patients

“…The beneficial effects of IL-18 production at the tumor site are mediated by NK cells and cytotoxic T cells, which elicit antitumor immune responses [6,7]. Chang et al [8] demonstrated that intratumoral injection of IL-18 DNA enhanced IFN-c production and caused regression of liver tumors.…”