Amplified interleukin-15 expression vectors for cancer immunogene therapy

Interleukin-15 (IL-15) is a pleiotropic cytokine that plays a key role in the regulation of both innate and adaptive immune responses. It promotes the survival, proliferation, activation and maintenance of natural killer and CD8+ T cells. It also stimulates the function of neutrophils, macrophages and dendritic cells, and could therefore be a potential cytokine for cancer immune therapy. The therapeutic effects of cytokines are related to their expression levels. In this study, we investigated an amplified IL-15 expression plasmid vector, pHi2-spIL15-CMV-tat, and a carcinoembryonic antigen (CEA)-positive tumor-specific amplified IL-15 expression plasmid vector, pHi2-spIL15-CEA-tat. In pHi2-spIL15-CMV-tat, IL-15 expression was driven by HIV2 LTR, which was transactivated by CMV promoter-controlled expression of HIV tat. In addition, the native IL-15 signal peptide was replaced by the IL-2 signal peptide to enhance its secretion. A significant amount of IL-15 expression was achieved when transfected into tumor cells in vitro. In order to target IL-15 expression in CEA-positive cells, the CEA promoter positively-controlled IL-15 expression plasmid vector pHi2-spIL15-CEA-tat was constructed by replacing the CMV with the CEA promoter. Efficient and targeted IL-15 expression was achieved in CEA-positive tumor cells by pHi2-spIL15-CEA-tat.