Development of adoptive immunotherapy by RNF43 specific T cell transfer in combination with dendritic cell
| Project/Area Number |
18590688
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kyushu University |
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Principal Investigator |
SUEHIRO Youko (2007) Kyushu University, Medical insitute of Bioregulation, Molecular Genetics, Assistant Professor (50380522)
久野 晃聖 (2006) 九州大学, 大学病院, 助手 (40380399)
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| Co-Investigator(Kenkyū-buntansha) |
TANI Kenzaburo KYUSHU UNIVERSITY, Medical institute of Bioregulation, Molecular Genetics, Professor (00183864)
末廣 陽子 九州大学, 生体防御医学研究所, 助手 (50380522)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | adoptive immunotherapy / RNF 43 peptide / regulatory T cells / dendritic cells / IL-2 / Colon cance / cyclophosphamide / 活性化リンパ球 / RNF43 / 特異的活性化リンパ球 / シクロフォスファミド |
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| Research Abstract |
The purpose of this Phase I clinical study is to observe the safety and the immunological and clinical responses induced by the combined administration of cyclophosphamide, tumor antigen RNF43 pulsed autologous dendritic cells, RNF43 specific autologous T cells and interleukin-2. Our preclinical data demonstrated that the T cells cocultured with RNF43 peptide pulse dendritic cells from peripheral blood of cancer patients had cytotoxic activity to RNF43 positive cell line, and the number of CD45RO and CCR7 was increased which suggested the induction of memory T cell population. After the start of clinical trial, RNF43 mRNA expression levels of 24 solid tumor candidate patients' biopsied samples were determined using real time PCR method. Only 5 colon cancer patients satisfied the inclusion criteria of elevated RNF43 mRNA expression level. So far, one patient of 60-year-old man with colon cancer with metastasis to lung and liver, was enrolled in this clinical trial and received RNF43 specific T cells with dendritic cells and IL-2. [CY 300 mg/m^2 (day-4), DC pulsed T cells 2x10^8 cells (day0), DC 1x10^7cells (day0, 7, 14), IL-2 (day 0, 1, 2, 7, 8, 9, 14, 15, 16)]. The patient was well tolerated and no major adverse events were observed. RNF43 specific CTL was observed after the adoptive cell administration. His clinical response was PD, namely the size of his lung metastasis was stable but that of liver metastasis was increased and the appearance of new brain metastasis. He passed away because of the liver failure after 2 months. Further study is required to determine the safety and clinical effects of this trial.
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Report
(3 results)
Research Products
(11 results)
