| Autor: |
Hasegawa, K, Tagawa, M, Takagi, K, Tsukamoto, H, Tomioka, Y, Suzuki, T, Nishioka, Y, Ohrui, T, Numasaki, M |
| Zdroj: |
Cancer Gene Therapy; August 2016, Vol. 23 Issue: 8 p266-277, 12p |
| Abstrakt: |
Interleukin (IL)-28A/interferon (IFN)-?2 and IL-29/IFN-?1 have been demonstrated to elicit direct and indirect anti-tumor actions. In this study, we constructed an adenovirus vector expressing either IL-28A/IFN-?2 (AdIL-28A) or IL-29/IFN-?1 (AdIL-29) to evaluate the therapeutic properties of intratumoral injection of recombinant adenovirus to apply for the clinical implementation of cancer gene therapy. Despite the lack of an anti-proliferative effect on MCA205 and B16-F10 cells, a retarded growth of established subcutaneous tumors was observed following multiple injections of either AdIL-28A or AdIL-29 when compared with AdNull. In vivocell depletion experiments displayed that both NK cells and CD8+T cells have a major role in AdIL-28A-mediated tumor growth suppression. A significant increase in the number of infiltrating CD8+T cells into the tumors treated with either AdIL-28A or AdIL-29 was observed. Moreover, specific anti-tumor cytotoxic T lymphocyte reactivity was detected in spleen cells from animals treated with either AdIL-28A or AdIL-29. In IFN-?-deficient mice, anti-tumor activities of AdIL-28A were completely impaired, indicating that IFN-? is critically involved in the tumor growth inhibition triggered by AdIL-28A. IL-12 provided a synergistic anti-tumor effect when combined with AdIL-28A. These results indicate that AdIL-28A and AdIL-29 could be successfully utilized as an alternative cancer immunogene therapy. |
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