title: 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.
authors.affiliation: Department of General Surgery, Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin 300052, PR China. humphreyhe@163.com
authors.forename: Xianghui
authors.initials: X
authors.lastname: He
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Linan
authors.initials: L
authors.lastname: Hou
authors.forename: Liwei
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D003587:Cytomegalovirus / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010957:Plasmids; D014162:Transfection
chemical_list: D002272:Carcinoembryonic Antigen; D019409:Interleukin-15