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.