Anti-cancer effect of engineered recombinant interleukin 18

Abstract

Background. Interleukin 18 (IL-18) is an inflammatory cytokine belonging to the interleukin 1 (IL-1) superfamily, and is known for its role in anti-cancer activity by promoting type 1 immune response, and thus may be applied to cancer immunotherapy. Our previous report has showed 16 times higher activity of engineered E6K+T63A IL-18 than of native IL-18 in vitro. However, no data has been acquired for its anti-cancer effect in animal model. Objectives. The objective of this study was to investigate the anti-cancer effect of engineered E6K+T63A IL-18 as an immune stimulant in vivo. Material and methods. Tumor-bearing mice were treated with native IL-18 or E6K or E6K+T63A IL-18 once a day for 10 days after the tumor reached the volume of 100 mm3. Tumor volume and the number of certain immune cell type in the tumor microenvironment were investigated in this study. Results. The results showed that tumor progression in mice treated with E6K+T63A was slower than in mice treated with E6K and native IL-18. The volume of the tumor was also smaller and the lifespan longer in the E6K+T63A IL-18-treated mice. The proportions of type 1 helper T cell (Th1) and cytotoxic T lymphocyte (CTL) were significantly higher in mice treated with E6K+T63A IL-18. Conclusions. These results suggest that our engineered IL-18 conferred strong anti-tumor immunity in the animal model.