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Accession number;07A0254970
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| Title;Potent Anti-tumor effects of Combination therapy using Interleukin-23 and .ALPHA.-galactosylceramide |
| Author;
KANEDA HIDE
(Nihon Univ. School Of Medicine)
SATO MARIMO
(Univ. Tokyo)
NANGO YOKO
(Nihon Univ. School Of Medicine)
KUSAFUKA TAKESHI
(Nihon Univ. School Of Medicine)
TAHARA HIDEAKI
(Univ. Tokyo)
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Journal Title;Journal of Nihon University Medical Association
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Journal Code:F0911A
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ISSN:0029-0424
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VOL.66;NO.1;PAGE.60-69(2007)
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| Figure&Table&Reference; |
| Pub. Country;Japan |
| Language;English |
| Abstract;Co-administration of .ALPHA.-galactosylceramide (.ALPHA.-GalCer) with Interleukin (IL)-12 augmented the anti-metastatic effects of either treatment alone in mice. This treatment was associated with the elevation of natural killer (NK) activity though the increase of interferon (IFN)-.GAMMA. activity. IL-23 is a relatively novel cytokine, which consists of a heterodimer of the IL-12p40 subunit and a novel p19 subunit. IL-23 has biological activities similar to but distinct from IL-12. IL-23 can enhance the proliferation of memory T cells and the production of IFN-.NU., IL-12, and tumor necrosis factor (TNF)-.ALPHA. from activated CD4+ T-cells. IL-23 is produced by dendritic cells and possesses potent anti-tumor and anti-metastatic activity in murine tumor models. We investigated the combined therapeutic effect of IL-23 and .ALPHA.-GalCer against highly metastatic B16F10 melanoma. This combinetion treatment of tumor-bearing mice induced an elevation of the serum IFN-.GAMMA. concentration at a much lower dose compared with the IL-12 treatment alone. IFN-.GAMMA. production was observed in CD4+ and CD8+ T-cells in the lymph nodes obtained from these mice upon stimulation with immobilized anti-CD3 mAb. In parallel with the augmented IFN-.GAMMA. production, the tumor-specific cytotoxic and NK activities were significantly augmented with the combined therapy. Furthermore, lymph nodes cells cultured with anti-CD3 mAb alone, or with .ALPHA.-GalCer and anti-CD3 mAb, produced high levels of IFN-.GAMMA. and IL-17. These findings suggest that the combination treatment using IL-23 and .ALPHA.-GalCer may activate both NKT cells and NK cells, and may have potent anti-metastatic effects. (author abst.) |
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