Immunotherapy for childhood leukemia and solid tumors using dendritic cells
| Project/Area Number |
18591191
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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 |
Pediatrics
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| Research Institution | Kyushu University |
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Principal Investigator |
MATSUZAKI Akinobu Kyushu University, Graduate School of Medical Sciences, Professor (90238999)
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| Co-Investigator(Kenkyū-buntansha) |
SUMINOE Aiko Kyushu University, Kyushu University Hospital, Assistant Professor (80335968)
KOGA Yuhki Kyushu University, Kyushu University Hospital, Assistant Professor (60398071)
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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 | dendritic cell / tumor antigen / child / immunotherapy / leukemia |
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| Research Abstract |
(1)Generation of leukemia cell-derived dendritic cells (DCs): In order to establish the effective immunotherapy using DCs, DCs were generated directly from leukemia cells. When primary leukemia blasts were cultured in the presence of GM-CSF, TNF- a , Flt-3 ligand, and IL-4, the blasts from the patients with AML M4 and M5a expressed CD 11c, CD80, CD83, CD86. These findings suggested that the leukemia cells of some AML subtypes can differentiate into DCs and might present leukemia-specific antigens directly to T lymphocytes.
(2) Expression of cytokine-associated genes in DCs: The expression of cytokine-associated genes in DCs derived from umbilical cord blood (UCB) and adult peripheral blood (APB) was compared. The expression of the Th1 response-related genes and chemokine genes was significantly lower in UCB-DCs than in APB-DC in both maturation states. Calgranulins A and B, which are speculated to induce immune tolerance, showed higher expression in UCB-DCs. The expression of particular genes related to immune responses was significantly different between UCB-and APB-DCs, which may cause functional difference in DC-mediated immunity between newborns and adults.
(3)The utility of recombinant Sendai virus(rSeV) for effective DC-mediated immunotherapy against childhood cancer; The ex vivo infection of immature DCs with rSeV induces their spontaneous maturation and activation. We tried to apply this result to the treatment for patients with childhood cancer to setablish a new powerful DC-mediated immunotherapy. Peripheral blood mononuclear cells were isolated from the children with cancer and were cultured in the presence 10% autologous serum, GM-CSF, IL-4 and TNF-α to generate DCs. When the generated DCs were infected with rSeV, the expression of CD80, CD83 and CD86 was markedly enhanced. These findings suggested that rSeV could be a powerful booster for DC-mediated cancer immunotherapy, which might improve the prognosis of children with cancer.
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Report
(3 results)
Research Products
(36 results)
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[Journal Article] Treatment-related acute myelomonocytic leukemia with t(11 ; 19) in a child following chemotherapy for hepatoblastoma2008
Author(s)
Koea, Y, Matsuzaki, A, Suminoe, A, Tajiri, T, Washitoh, N, Hara, T, Taguchi, T, Hara, T
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Journal Title
Pediatr Blood Cancer 50
Pages: 943-944
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Fatal visceral varicella-zoster virus infection without skin involvement in a child with acute lymphoblastic leukemia2008
Author(s)
Matsuzaki, A, Suminoe, A, Koga, Y, Kusuhara, K, Hara, T, Ogata, R, Sata, T, Hara, T
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Journal Title
Pediatr Hematol Oncol 25
Pages: 237-242
Description
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[Journal Article] Expression and production of aberrant PAX5 with deletion of exon 8 in B-lineage acute lymphoblastic leukaemia of children2007
Author(s)
Sadakane, Y, Zaitsu, M, Nishi, M, Sugita, K, Mizutani, S, Matsuzaki, A, Sueoka, E, Hamasaki, Y, Ishii, E
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Journal Title
Br J Haematol 136
Pages: 297-300
Description
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[Journal Article] Expression of matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) genes in blasts of infant acute lymphoblastic leukemia with organ involvement2007
Author(s)
Suminoe, A, Matsuzaki, A, Hattori, H, Koga, Y, Ishii, E, Hara, T
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Journal Title
Leuk Res 31
Pages: 1437-1440
Description
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[Journal Article] Regulatory polymorphisms of multidrug resistance 1 (MDR1) gene are associated with the development of childhood acute lymphoblastic leukemia2007
Author(s)
Hattori, H, Suminoe, A, Wada, M, Koga, Y, Kohno, K, Okamura, J, Hara, T, Matsuzaki, A
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Journal Title
LeukRes 31
Pages: 1633-1640
Description
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[Journal Article] 初発時に急性白血病様の骨髄像を呈した原発不明胞巣型横紋筋肉腫2007
Author(s)
山口敢, 古賀友紀, 住江愛子, 齋藤祐介, 松崎彰信, 神野俊介, 瀧本智仁, 須田正洋, 小田義直, 武藤敏孝, 高月浩, 原寿郎
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Journal Title
NAID
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[Journal Article] Long-term use of peripherally inserted central venous catheters for cancer chemotherapy in children2006
Author(s)
Matsuzaki, A, Suminoe, A, Koga, Y, Hatano, M, Hattori, S, Hara, T
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Journal Title
Support Care Cancer 14
Pages: 153-160
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of novel genes with prognostic value in childhood leukemia using cDNA microarray and quantitative RT-PCR2006
Author(s)
Hattori, H, Matsuzaki, A, Suminoe, A, Koea, Y, Tashiro, K, Hara, T
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Journal Title
Pediatr Hematol Oncol 23
Pages: 115-127
Description
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[Presentation] Association of regulatory polymorphisms of multidrug resistance 1(MDR1) gene with the development of childhood acute lymphoblastic leukemia2007
Author(s)
Hattori, H, Suminoe, A, Wada, M, Koga, Y, Okamura, J, Hara, T, Matsuzaki, A
Organizer
The 3rd Congress of Asian Society for Pediatric Research
Place of Presentation
Tokyo, Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Expression of matrix metalloproteinase(MMP).and tissue inhibitor of MMP(TIMP) genes in blasts of infant ALL with organ involvement2007
Author(s)
Suminoe, A, Matsuzaki, A, Hattori, H, Koga, Y, Hara, T
Organizer
The 3rd Congress of Asian Society for Pediatric Research
Place of Presentation
Tokyo, Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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