Project/Area Number |
23591613
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Dermatology
|
Research Institution | University of Yamanashi |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
INOZUME Takashi 山梨大学, 医学部附属病院, 助教 (80334853)
HANAWA Fumie 山梨大学, 医学部附属病院, 助教 (80535592)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
|
Keywords | 腫瘍免疫 / 悪性黒色腫 / ワクチン / 皮膚腫瘍 / 癌免疫療法 / STAT3 / メラノーマ / がん免疫 |
Research Abstract |
We revealed that STAT3-restricted cytokines, especially IL-6 from B16 melanoma cells suppressed IFN-gamma-production in both CD4+ and CD8+ T-cells. In culture, IL-6 from B16 cells was reduced by pretreatment with rR9-GRIM19. In vivo, although intratumoral injections of rR9-GRIM19 elicited anti-B16 effects with frequencies of IL-6-producing T-cell phenotypes, complete B16 regression was not observed. 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 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 production occurred in COG-treated B16-bearing. We finally confirmed that rIFN exposure could significantly enhance rR9-GRIM19-treated anti-B16 melanoma effects in vitro and in vivo.
|