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Immunotherapy for childhood leukemia and solid tumors using dendritic cells

Research Project

Project/Area Number 18591191
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKyushu University

Principal Investigator

MATSUZAKI Akinobu  Kyushu University, Graduate School of Medical Sciences, Professor (90238999)

Co-Investigator(Kenkyū-buntansha) SUMINOE Aiko  Kyushu University, Kyushu University Hospital, Assistant Professor (80335968)
KOGA Yuhki  Kyushu University, Kyushu University Hospital, Assistant Professor (60398071)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
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)
Keywordsdendritic cell / tumor antigen / child / immunotherapy / leukemia
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.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (36 results)

All 2008 2007 2006

All Journal Article (29 results) (of which Peer Reviewed: 14 results) Presentation (6 results) Book (1 results)

  • [Journal Article] Treatment-related acute myelomonocytic leukemia with t(11;19) in a child following chemotherapy for hepatoblastoma2008

    • Author(s)
      Koga Y, Matsuzaki A, Suminoe A, Tajiri T, Washitoh N, Hara T, Taguchi T, Hara T
    • Journal Title

      Pediatric Blood & Cancer 50

      Pages: 943-944

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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
    • Journal Title

      Pediatric Hematology/Oncology 25

      Pages: 237-242

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression of cytokine-associated genes in dendritic cells (DCs): Comparison betweenadult peripheral blood- and umbilical cord blood-derived DCs by cDNA microarray2008

    • Author(s)
      Koga Y, Matsuzaki A, Suminoe A, Hattori H, Hara T
    • Journal Title

      Immunology Letters 116

      Pages: 55-63

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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
    • Journal Title

      Pediatr Blood Cancer 50

      Pages: 943-944

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Journal Title

      Pediatr Hematol Oncol 25

      Pages: 237-242

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of cytokine associated genes in dendritic cells (DCs) : Comparison between adult peripheral blood- and umbilical cord blood-derived DCs by cDNA microarray2008

    • Author(s)
      Koea, Y, Matsuzaki, A, Suminoe, A, Hattori, H, Hara, T
    • Journal Title

      Immunol Lett 116

      Pages: 55-63

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of cytokine-associated genes in dendritic cells(DCs):Comparison between adult peripheral blood-and umbilical cord blood-derived DCs by cDNA microarray2008

    • Author(s)
      Koga Y, Matsuzaki A, Suminoe A, Hattori H, Hara T
    • Journal Title

      Immunology Letters 116

      Pages: 55-63

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      British Journal of Haematology 136

      Pages: 297-300

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Outcome of non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation from family donors in children and adolescents2007

    • Author(s)
      Yoshihara T, Okada K, Matsuzaki A, et. al.
    • Journal Title

      International Journal of Hematology 85

      Pages: 246-255

    • NAID

      10019489005

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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
    • Journal Title

      Leukemia Research 31

      Pages: 1437-1440

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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
    • Journal Title

      Leukemia Research 31

      Pages: 1633-1640

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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、査賀 友紀、住江 愛王、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
    • Journal Title

      臨床血液 48

      Pages: 315-320

    • NAID

      10019923754

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Human herpesvirus 6 (HHV-6)-associated pleurisy after unrelated cord blood transplantation in children with chemotherapy-resistant malignant lymphoma2007

    • Author(s)
      Suminoe A, Matsuzaki A, Koaa Y, Kusuhara K, Hara T
    • Journal Title

      Journal of Pediatric Hematology/Oncology 29

      Pages: 709-712

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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
    • Journal Title

      Br J Haematol 136

      Pages: 297-300

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Outcome of non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation from family donors in children and adolescents2007

    • Author(s)
      Yoshihara, T, Okada, K, Matsuzaki, A, et. al.
    • Journal Title

      Int J Hematol 85

      Pages: 246-255

    • NAID

      10019489005

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Journal Title

      Leuk Res 31

      Pages: 1437-1440

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Journal Title

      LeukRes 31

      Pages: 1633-1640

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Human herpesvirus 6 (HHV-6)-associated pleurisy after unrelated cord blood transplantation in children with chemotherapy-resistant malignant lymphoma2007

    • Author(s)
      Suminoe, A, Matsuzaki, A, Koea, Y, Kusuhara, K, Hara, T
    • Journal Title

      J Pediatr Hematol Oncol 29

      Pages: 709-712

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of matrix metalloproteinase(MMP)and tissue inhibitor of MMP(TIMP)genes in blasts of infant acute lymphoblastic leukemia with orsan involvement2007

    • Author(s)
      Suminoe A, Matsuzaki A, Hattori H, Koea Y. Ishii E, Hara T
    • Journal Title

      Leukemia Research 31

      Pages: 1437-1440

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      Leukemia Research 31

      Pages: 1633-1640

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      Br J Haematol 136

      Pages: 297-300

    • Related Report
      2006 Annual Research Report
  • [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
    • Journal Title

      Leukemia Res (in press)

    • Related Report
      2006 Annual Research Report
  • [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
    • Journal Title

      臨床血液 (印刷中)

    • NAID

      10019923754

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Long-term use of peripherally inserted central venous catheters (PICCs) for cancer chemotherapy in children2006

    • Author(s)
      Matsuzaki A, Suminoe A, Koea Y, Hatano M, Hattori S, Hara T
    • Journal Title

      Supportive Care in Cancer 14

      Pages: 153-160

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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
    • Journal Title

      Pediatric Hematology Oncology 23

      Pages: 115-127

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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
    • Journal Title

      Support Care Cancer 14

      Pages: 153-160

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Journal Title

      Pediatr Hematol Oncol 23

      Pages: 115-127

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Long-term use of peripherally inserted central venous catheters (PICCs) for cancer chemotherapy in children2006

    • Author(s)
      Matsuzaki A, Suminoe A, Koga Y, Hatano M, Hattori S, Hara T
    • Journal Title

      Supportive Care in Cancer 14

      Pages: 153-160

    • Related Report
      2006 Annual Research Report
  • [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, Koga Y, Tashiro K, Hara T
    • Journal Title

      Pediatr Hematol Oncol 23

      Pages: 115-127

    • Related Report
      2006 Annual Research Report
  • [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(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Related Report
      2007 Final Research Report Summary
  • [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
      2007 Final Research Report Summary
  • [Presentation] Treatment results of relapsed childhood ALL: A report from the Kyushu-Yamaguchi Children's Cancer Study Group2006

    • Author(s)
      Matsuzaki A
    • Organizer
      The 26th Korean Society of Pediatric Hematology Oncology Spring Meeting
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2006-04-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Treatment results of relapsed childhood ALL : A report from the Kyushu-Yamaguchi Children's Cancer Study Group2006

    • Author(s)
      Matsuzaki, A
    • Organizer
      The 26th Korean Society of Pediatric Hematology Oncology Spring Meeting
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2006-04-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 治療成績に影響を及ぼす要因:II.宿主要因:薬理動態および薬理遺伝学日本小児血液学会編:小児白血病・リンパ腫の診療ガイドライン2007年版2007

    • Author(s)
      松崎 彰信
    • Publisher
      金原出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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