Inhibition of colon tumor growth by IL-15 immunogene therapy

Abstract

Interleukin-15 is a pleiotropic cytokine that has potential for cancer immunegene therapy. We previously reported the construction and characterization of IL-15 overexpression vectors pHi2-IL15-CMV-tat (L1) and pHi2-spIL15-CMV-tat (L3), as well as carcinoembryonic antigen promoter-amplified IL-15 expression plasmid vectors pHi2-IL15-CEA-tat (L2) and pHi2-spIL15-CEA-tat (L4). In the current study, we evaluated the expression and therapeutic efficacy of these vectors using a mouse colon carcinoma model. Plasmid vectors were transfected into SW480 and MCF-7 cells, and IL-15 overexpression was confirmed. IL-15 expressed by transfected tumor cells stimulated spleen cell proliferation in vitro. Intraperitoneal injection of plasmid pHi2-spIL15-CMV-tat (L3) into mice resulted in transgene expression by peritoneal mesothelial cells, inhibited CT-26 tumor growth and prolonged the survival of tumor-bearing mice. In addition, the in vivo transfection of plasmid pHi2-spIL15-CMV-tat (L3) via electroporation slowed the tumor formation of subcutaneously inoculated CT-26 cells. These data suggest that IL-15 overexpression achieves therapeutic effects in a mouse cancer model and that these gene transfer approaches should be further evaluated for use in the treatment of human cancers.