Potent antitumor immunotherapy mediated by IL-18 gene transfection to PAM212 cells

点击翻译按钮获取中文摘要

Increased number of oral cancer patient is currently consideration, which in Spite of developing operation technique and chemotherapy. Cancer gene therapy is one of new approaches against oral cancer. Initiation of the adaptive immune response is believed to be a result of local necrotic and apoptotic death of tissues and release of inflammatory cytokines by resident macrophages and recruited plymorphonuclear leukocytes. The cytokines released at the tumor site include IL-1, IL-6, IL-12 and IL-18, and other cytokines and chemokines. Dendritic cell recruitment and maturation is required for the induction of immune response. IL-18, INF-g-inducing factor, is a stimulatory factor in activation of Th1 cells that are major INF-g producing cells at tumor site. INF-g is up-regulate MHC class I and II expression on tumor cells. MHC class I is activated NK cells and macrophages and to help generate CD8+ cytotoxic T cells. In this study, IL-18 gene transfer to mouse squamous cell carcinoma cell (PAM212) was used to deliver cytokine to the tumor microenvironment. IL-18 single gene transfection of tumor cell ex vivo resulted in minimum effect of tumor regression, To generate active form of IL-18, it needs to IL-1b converting enzyme (ICE) to cleaved intercellular cysteine residue. Thus, dual transfection of IL-18 and ICE was performed in this study. Dual gene transfection study of tumor cell ex vivo resulted in 20% effect of tumor regression that was out of our respect. The reason of these results may be related to the transfection efficiency of the genes to PAM212 cells. We also injected ICE to IL-18/PAM212 bearing mouse, resulted in death of all animals because of toxicity. Therefore, future study required for develop the technique of transfection efficiency in the squamous cell carcinoma.