| Project/Area Number |
25861253
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory surgery
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
ZHANG Rong 愛知県がんセンター(研究所), 腫瘍免疫学部, リサーチレジデント (00643719)
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| Research Collaborator |
KUZUSHIMA Kiyotaka 愛知県がんセンター研究所, 部長 (30311442)
UEMURA Yasushi 国立がんセンター, ユニット長 (40364781)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肺がん / 免疫 / 遺伝子療法 / 細胞療法 / がん / 遺伝子治療 / 癌 / 外科 |
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| Outline of Final Research Achievements |
Adoptive immunotherapy using TCR gene-modified T cells is an attractive strategy for targeting cancer. However, naturally occurring TCRs are of lower affinity, a fact that limits the ability of natural TCRs to recognize the low antigen-HLA levels typically expressed on tumor cells. To address this issue, we used invariant NKT (iNKT) cells, a unique subset of T cells that recognize α-GalCer presented by CD1d, as a cellular adjuvant. We found that soluble factors from iNKT cell/α-GalCer-dendritic cell (DC) interaction enhanced the HLA-I expression on cancer cells and upregulated both perforin and granzyme B in TCR gene-modified T cells, in turn enhancing the potency of cellular immunity. Furthermore, in vivo transfer of TCR gene-modified T cells in combination with iNKT/α-GalCer-DC inhibited the tumor growth and significantly prolonged the survival in xenograft model. Thus, the additional transfer of iNKT/α-GalCer-DC may improve the efficacy of TCR gene-modified T cells.
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