Tumor secreting high levels of IL-15 induces specific immunity to low immunogenic colon adenocarcinoma via CD8+ T cells.
Although interleukin (IL)-15 augments innate and acquired immunities, IL-15 expression is controlled at the levels of transcription, translation and intracellular trafficking. We constructed plasmid vectors encoding the murine mature-IL-15 cDNA linked to an Igkappa leader sequence and full-length murine IL-15 cDNA to evaluate the efficacy of the mature-IL-15 vector. Weakly immunogenic colon 26 cells were transfected with the above-mentioned vectors or with empty vector (mock). Transfectants with mature-IL-15 produced significantly higher levels of IL-15 than did transfectants with full-length IL-15. When injected into syngeneic BALB/c mice, transfectants secreting high levels of IL-15 were rejected completely. Depletion of natural killer cells or CD4+ T cells did not affect the growth of transfectants. In contrast, transfectants treated with anti-CD8 antibody re-grew 1 month later after implantation. These findings indicate that CD8+ T cells are required for complete rejection of the tumor. Gene therapy with transfectants expressing mature-IL-15 containing the Igkappa leader sequence may be useful as a tumor vaccine.
Araki
Atsuhiro
A
Department of Surgery II, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Hazama
Shoichi
S
Yoshimura
Kiyoshi
K
Yoshino
Shigefumi
S
Iizuka
Norio
N
Oka
Masaaki
M
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D015704:CD4 Antigens; D016827:CD8 Antigens; D019496:Cancer Vaccines; D019409:Interleukin-15; D012333:RNA, Messenger