| Project/Area Number |
24791145
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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 |
Dermatology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
HANAWA Fumie 山梨大学, 医学部附属病院, 助教 (80535592)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 皮膚科学 / 皮膚腫瘍学 / 悪性黒色腫 / 腫瘍免疫 / STAT3 / STAT3阻害薬 |
|---|
| Research Abstract |
Crosstalk between cancer cells and immune cells in established cancer microenvironment leads to the restriction of immune responses via phosphorylated STAT3 (pSTAT3). To inhibit STAT3-mediated signaling cascades in cancer microenvironment, we generated rR9-GRIM19 fusion proteins. To elicit complete B16 regression, we investigated the antitumor effects of combination immunotherapies with rR9-GRIM19. rR9-GRIM19 elicited enhanced antitumor effects when combined either with rR9-OVA (as our Th1/Tc1-inducible adjuvant) or CpG-ODN, but only the combination of CpG-ODN, rR9-OVA, and rR9-GRIM19 (COG therapy) elicited complete B16 tumor regression. Interestingly, melanoma-specific cytotoxic T lymphocyte (CTL) expansion with IFN-g production occurred in COG-treated B16-bearing. our results indicate that strong antitumor effects could be elicited when the cancer microenvironment was simultaneously exposed with STAT3 inhibitor and STAT1 activator (Tc1/Th1-inducible adjuvants).
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