Project/Area Number |
16390352
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General surgery
|
Research Institution | Tohoku University |
Principal Investigator |
EGAWA Shinichi Tohoku University, Tohoku University, Associate Professor (00270679)
|
Co-Investigator(Kenkyū-buntansha) |
FUKUYAMA Shoji Tohoku University, Hospital, Assistant Professor (10344673)
MOTOI Fuyuhiko Tohoku University, Hospital, Assistant Professor (30343057)
OKADA Takaho Tohoku University, Hospital, Assistant Professor (10375074)
SAKATA Naoaki Tohoku University, Hospital, Assistant Professor (50431565)
砂村 眞琴 東北大学, 大学院医学系研究科, 非常勤講師 (10201584)
阿部 忠義 東北大学, 病院・助手 (50361077)
武田 和憲 東北大学, 大学院・医学系研究科, 助教授 (20171639)
横山 忠明 東北大学, 病院・助手
|
Project Period (FY) |
2004 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥15,250,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2007: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥3,700,000 (Direct Cost: ¥3,700,000)
|
Keywords | pancreatic cancer / SEREX method / cancer antigen / immunotherrapy / dendritic cells / interferon alpha / clinical trial / intralymphatic injection / IL-12 / WT1 / survivin / 腫瘍抗原 / IFN-α / 抗原負荷 / ティッシューアレイ / 免疫療法 / SEREX / マイクロアレイ / 発現プロファイル |
Research Abstract |
We have performed intra-operative local injection of autologous dendritic cell immediately after intra-operative irradiation of the primary tumor in patients with pancreatic cancer with liver metastases. This preliminary immunotherapy resulted in a partial regression of liver metastases and prolongation of survival in two patients. Using sera of patients with pancreatic cancer in SEREX method, we have identified a novel cancer-testis antigen, KU-CT-1, that was expressed in 30% of this deadly disease. Of 20 patients with pancreatic cancer, 3 patients harbored specific antibody for KU-CT-1. We made tissue miro-array to confirm the frequency of KU-ST-1 and broad-spectrum cancer antigen, such as WT1 and survivin. Although the expression frequency and intensity was not so high, these data suggested the possible targeting immunotherapy against pancreatic cancer. Dendritic cells were induced from the peripheral monocytes from patients with advanced pancreatic cancer and maturated in the presence of IFN-alpha, IFN-gamma, TNF-alpha, IL-1beta and poly I:C. The phenotype and the ability to produce IL-12p70 of these dendritic cells indicated that dendritic cells from advanced disease can be skewed to be cytotoxic. Phase I trial of intralymphatic administration of cytotoxically skewed dendritic cells showed safety and warranted antigen loaded specific immunotherapy for pancreatic cancer.
|