title: Interleukin (IL)-21 and IL-15 genetic transfer synergistically augments therapeutic antitumor immunity and promotes regression of metastatic lymphoma.
abstract: IL-21 supports proliferation of mature T and B cells and facilitates expansion and maturation of natural killer (NK) cells in synergy with IL-15. However, the biological implications of IL-21 in vivo have not been fully elucidated. IL-21 and IL-15 expression plasmids were intravenously injected under high pressure into the tail veins of mice, which were subsequently challenged by an intravenous injection of RLmale1 lymphoma cells. The IL15 gene transfection significantly reduced the numbers of metastatic tumor foci in the liver. In contrast, when IL21 and IL15 genes were cotransfected, complete regression was achieved in 80% of the mice. The cytokine gene therapy was also performed in mice that had been intravenously inoculated with the tumor cells. Forty percent of mice that received a single injection of a mixture of cytokine genes successfully rejected the preestablished metastatic lymphoma and showed tumor-free survival for more than 300 days. IL-21 significantly elevated the cytotoxic T lymphocyte activity in the spleens of tumor-inoculated mice, while the two cytokines augmented NK killing activity in a synergistic manner. These results strongly suggest that the codelivery of IL-21 and IL-15 elicits powerful antitumor immune responses, resulting in marked therapeutic efficacy against metastatic tumors.
authors.affiliation: Department of Microbiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Asada
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Itokawa
authors.forename: Feng-De
authors.initials: FD
authors.lastname: Cui
authors.forename: Masaharu
authors.initials: M
authors.lastname: Shin-Ya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Gojo
authors.forename: Kakei
authors.initials: K
authors.lastname: Yasutomi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ueda
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Yamagishi
authors.forename: Jiro
authors.initials: J
authors.lastname: Imanishi
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
mesh_terms: D000818:Animals; D015316:Genetic Therapy; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008223:Lymphoma / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D000098546:Interleukin-21
chemical_list: D019409:Interleukin-15; D007378:Interleukins; D000098546:Interleukin-21