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Irtercellular molecular transfer of OX40 in novel anti-tumor immunotherapy

Research Project

Project/Area Number 14570417
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

BABA Eishi  KYUSHU UNIVERSITY, University Hospital, Research Associate, 大学病院, 助手 (00315475)

Co-Investigator(Kenkyū-buntansha) MORISAKI Takashi  KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究院, 助手 (90291517)
KATANO Mitsuo  KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Professor, 大学院・医学研究院, 教授 (10145203)
TANAKA Yuetsu  Ryukyu University, Faculty of Medicine, Professor, 医学部, 教授 (30163588)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsTumor Immunoloav / T lymphocytes / Antigen presenting cells / OX40 / Intercellular molecular transfer / Dendritic cells / 癌ワクチン療法
Research Abstract

Various immunotherapy against malignant tumors by using antigen presenting cells, such as monocytes-derived dendritic cells, had been examined. The present study was designed to analyze the mechanism of intercellular molecular transfer of OX40 between T lymphocytes and antigen presenting cells in order to improve the clinical efficacy of the immunotherapies. OX40/OX40L interaction was known to provide an important regulatory mechanism in both T cell-vascular endothelial cell adhesion and antigen-specific immune reactions. In this study, we showed that OX40, originally expressed on activated CD4^+ T cells, can be transferred to the cell surface of OX40L-expressing cells. In addition, we found that not only a 50 kDa authentic OX40 (p50) but also a 35 kDa OX40-related glycoprotein (p35 OX40rgp), which had altered glycosilations, were expressed on the surface of primary activated CD4^+ T cells and OX40-expressing cell lines. Intercellular transfer analysis showed that OX40L-dependent intercellular OX40-transfer occurs under physiological conditions, and that the transfer is possibly mediated by two istinct manners. We also analyzed the interaction between T lymphocytes and monocyte-derived dendritic cells obtained from malignant tumor patients who had autologous tumor lysate-pulsed dendritic cells therapy. Cancer patients were revealed to possess the subpopulation of monocyte-derived dendritic cell with impaired cell survival, cytokine production and antigen-presentation. These findings might provide information of the difficulties of immunotherapy for cancer patients.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (25 results)

All 2004 2003 2002 Other

All Journal Article (20 results) Publications (5 results)

  • [Journal Article] Monocyte-derived dendritic cells that capture dead tumor cells secrete IL-12 and TNF-alpha through IL-12/TNF-alpha/NF-kappaB autocrine loop2004

    • Author(s)
      Onishi H et al.
    • Journal Title

      Cancer Immunol Immunother 53

      Pages: 1093-1100

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Phase I study of CPT-11 and bolus 5-FU/1-leucovorin in patients with metastatic colorectal cancer2004

    • Author(s)
      Fujishima et al.
    • Journal Title

      Int J Clin Oncol. 9

      Pages: 92-97

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Three-dimensional two-layer collagen matrix gel culture model for evaluating complex biological functions of monocyte-derived dendritic cells2004

    • Author(s)
      Tasaki A et al.
    • Journal Title

      J Immunol Methods 287

      Pages: 79-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Protection against methotrexate toxicity by a soybean protein- and omega-3 fatty acid-containing diet : comparative study with a casein-containing diet.2004

    • Author(s)
      Mitsugi K et al.
    • Journal Title

      Oncol Rep. 12

      Pages: 41-45

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Phase I study of CPT-11 and bolus 5-FU/1-leucovorin in patients with metastatic colorectal cancer.2004

    • Author(s)
      Fujishima H, Kikuchi I, Miyanaga 0 Ueda A, Baba-E, Mitsugi K, Harada M, Nakano S.
    • Journal Title

      Int J Clin Oncol. 2004 9(2)

      Pages: 92-97

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Monocyte-derived dendritic cells that capture dead tumor cells secrete IL-12 and TNF-alpha through IL-12/ TNF-alpha/ NF-kappaB autocrine loop.2004

    • Author(s)
      Onishi H, Kuroki H, Matsumoto K, Haba.E, Sasaki N, Kuga H, Tanaka M, Katano M, Morisaki T.
    • Journal Title

      Cancer Immunol Immunother 53

      Pages: 1093-1100

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Protection against methotrexate toxicity by a soybean protein- and omega-3 fatty acid-containing diet : comparative study with a casein-containing diet.2004

    • Author(s)
      Mitsugi K, Nakamura T, Kashiwabara N, Ariyama H, Tanaka R, Baba-F, Nakamura M, Harada M, Nakano S.
    • Journal Title

      Oncol Rep. 12(1)

      Pages: 41-45

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Three-dimensional two-layer collagen matrix gel culture model for evaluating complex biological functions of monocyte-derived dendritic cells.2004

    • Author(s)
      Tasaki A, Yamanaka N, Kubo M, Matsumoto K, Kuroki H, Nakamura K, Nakahara C, Onishi H, Kuga H, Baba E, Tanaka M, Morisaki T, Katano M.
    • Journal Title

      J Immunol Methods 287(1-2)

      Pages: 79-90

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Cyclosporin-A enhances docetaxel-induced apoptosis through inhibition of NF-kB activation in human gastric carcinoma cells2003

    • Author(s)
      Nakahara et al.
    • Journal Title

      Clinical Cancer Research 9

      Pages: 5409-5416

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Combination of adoptive immunotherapy with herceptin for patients with Her2-expressing breast cancer2003

    • Author(s)
      Kubo et al.
    • Journal Title

      Anticancer Research 23

      Pages: 4443-4449

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Combined immunotherapy with intracavital injection of activated lymphocytes, monocyte-derived dendritic cells and low-dose2003

    • Author(s)
      Morisaki T et al.
    • Journal Title

      Anticancer Research 23

      Pages: 4459-4465

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Streptococcal preparation OK-432: a new maturation factor of monocyte-derived dendritic cells for clinical use2003

    • Author(s)
      Kuroki H et al.
    • Journal Title

      Cancer Immunology Immunother 52

      Pages: 561-568

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Dendritic cell-based combined immunotherapy with autologous tumor-pulsed dendritic cell vaccine and activated T cells for cancer patients : rationale, current progress, and perspectives2003

    • Author(s)
      Morisaki T et al.
    • Journal Title

      Human Cell 16

      Pages: 175-182

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Cyclosporin-A enhances docetaxel-induced apoptosis through inhibition of nuclear factor-kB activation in human gastric carcinoma cells.2003

    • Author(s)
      Nakahara C, Nakamura K, Yamanaka N, Haba E, Wada M, Matsunaga H, Noshiro H, Tanaka M, Morisaki T, Katano M.
    • Journal Title

      Clin Cancer Res. 9(14)

      Pages: 5409-5416

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Streptococal preparation OX-432 : a new maturation factor of monocyte-derived dendritic cells for clinical use.2003

    • Author(s)
      Kuroki H, Morisaki T, Matsumoto K, Onishi H, Baba F, Tanaka M, Katano M.
    • Journal Title

      Cancer Immunol Immunother 52

      Pages: 561-568

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Combined immunotherapy with intracavital injection. of activated lymphocytes, monocyte-derived dendritic cells and low-dose OK-432 in patients with malignant effusion.2003

    • Author(s)
      Morisaki T, Matsumoto K, Kuroki H, Kubo M, Baba E, Onishi H, Tasaki A, Nakamura M, Inaba S, Katano M.
    • Journal Title

      Anticancer Res. 23(6a)

      Pages: 4459-4465

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Combination of adoptive immunotherapy with Herceptin for patients with HER2-expressing breast cancer.2003

    • Author(s)
      Kubo M, Morisaki T, Kuroki H, Tasaki A, Yamanaka N, Matsumoto K, Nakamura K, Onishi H, BabaE, Katano M.
    • Journal Title

      Anticancer Res. 23(6a)

      Pages: 4443-4449

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Dendritic cell-based combined immunotherapy with autologous tumor-pulsed dendritic cell vaccine and activated T cells for cancer patients : rationale, current progress, and perspectives. Review.2003

    • Author(s)
      Morisaki T, Matsumoto K, Onishi H, Kuroki H, BabaE, Tasaki A, Kubo M, Nakamura M, Inaba S, Yamaguchi K, Tanaka M, Katano M.
    • Journal Title

      Hum Cell 16(4)

      Pages: 175-182

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Dysfunctional and short-lived subsets in monocyte-derived dendritic cells from patients with advanced cancer2002

    • Author(s)
      Onishi H et al.
    • Journal Title

      Clin Immunol 105

      Pages: 286-295

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Dysfunctional and short-lived subsets in monocyte-derived dendritic cells from patients with advanced cancer2002

    • Author(s)
      Hideya Onishi, Takashi Morisaki, Eishi Baba, Hirotaka Kuga, Hideo Kuroki, Kotaro Matsumoto, Masao Tanaka, Mitsuo Katano
    • Journal Title

      Clin Immunol 105

      Pages: 286-295

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakahara et al.: "Cyclosporin-A enhances docetaxel-induced apoptosis through inhibition of NF-kB activation in human gastric carcinoma cells"Clinical Cancer Research. 9. 5409-5416 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kubo et al.: "Combination of adoptive immunotherapy with herceptin for patients with Her2-expressing breast cancer"Anticancer Research. 23. 4443-4450 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Morisaki T et al.: "Combined immunotherapy with intracavital injection of activated lymphocytes, monocyte-derived dendritic cells and low-dose OK432 in patients"Anticancer Research. 23. 4459-4466 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuroki H et al.: "Streptococcal preparation OK-432 : a new maturation factor of monocyte-derived dendritic cells for clinical use"Cancer Immunology Immunotherapy. 52. 561-568 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Onishi H, Baba E, et al.: "Dysfunctional short-lived subsets in monocyte-derived dendritic cells from patients with advanced cancer"Clinical Immunology. 105. 286-295 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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