Immuno-gene Therapy Using Colon Cancer Cells Transfeeted with Mature-interleukin-18 cDNA and Ig k Leader Sequence

Interleukin (IL)-18 is a novel cytokine that induces interferon (IFN)-ν secretion and plays an important role in anti-tumor immunity. In the present study, we constructed plasmid vectors encoding the murine mature-IL-18 cDNA linked with the Igk leader sequence and the pro-IL-18-producing estimate the efficacy of the mature-IL-18 vector and to evaluate IL-18=producing tumor cells as a tumor vaccine. Colon 26 cells were transfected with the above mentioned vectors or with vector alone (mock). The ability of the culture supernatants of mature-IL-18 transfectants to induce IFN-ν secretion was extremely high in comparison to that of pro-IL-18 transfectants. When injected into syngeneic BALB/c mice, the growth of mature-IL-18 transfectants, but not pro-IL-18 transfectants, was significantly less than that in mock transfected cells (p＜0.01, by ANOVA and analysis of covariance). Depletion of natural killer cells did not affect the growth of transfectants. The growth inhibitory effects were partially abrogated following treatment with anti-CD4＋ and anti-CD8＋ antibodies. These date suggest that the rejection of mature-IL-18/colon 26 cells was mediated through T cell activation. Gene therapy using mature-IL-18 transfectants containing a plasmid vector and the Igκ　leader sequence may be a useful tumor vaccine.

IL-18

gene therapy

plasmid

immunotherapy