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Preparation of activated dendritic cells capable of priming tumor-specific cytotoxic T lymphocytes in patients with metastatic cancer using penicillin-killed streptococcus pyogenes (OK432) and anti-CD40 antibody

Research Project

Project/Area Number 17591475
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKagawa University

Principal Investigator

KONTANI Keiichi  Kagawa University, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (90314153)

Co-Investigator(Kenkyū-buntansha) YOKOMISE Hiroyasu  Kagawa University, Faculty of Medicine, Professor, 医学部, 教授 (80231728)
HUANG Cheng-long  Kagawa University, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (10271511)
YAMAUCHI Akira  Kagawa University, Faculty of Medicine, Professor, 医学部, 教授 (00291427)
木原 実  香川大学, 医学部附属病院, 助手 (50322269)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordscancer vaccine / immunotherapy / dendritic cell / tumor antigen / cytokine / 外科 / 樹状制帽 / 細胞ワクチン / 乳癌・肺癌
Research Abstract

In order to achieve sufficient therapeutic potency, it has been proposed that vaccine therapy with dendritic cells needs to be combined with manipulation of immunological checkpoints, such as inhibition of regulatory T cells and blockade of negative signals, and enhancement of T cell trafficking to tumor sites. In the combinatorial cancer immunotherapy, use of matured/activated dendritic cells (DCs) with more potent antigen presenting capacity seems to be essential for eliciting anti-tumor immune responses. We herein established an ex vivo induction strategy for activated DCs capable of eliciting efficient tumor antigen-specific cytotoxic T lymphocytes (CTLs) from patients with metastatic cancer as well as healthy donors. Immature DCs were matured by 48 h-culture in the presence of anti-CD40 antibody and penicillin-killed streptococcus pyogenes (0K432). Supplementation with both anti-CD40 antibody and OK432 resulted in induction of activated DCs with higher surface expression of CD80, CD83, CD86 and major histocompatibility complex (MHC) class II antigens, compared with other mature DCs that were induced by the combination of anti-CD40 with tumor necrosis factor-alpha (TNF-a) or lipopolysaccharide (LPS). In analysis of the produced cytokine profiles, the activated DCs produced the highest T-helper 1 (Th1)-type cytokines for at least 72 h. Furthermore, the activated DCs, pulsed with tumor-associated antigen (TAA) peptide, elicited in vitro tumor-specific CTLs, but DCs prepared with other combinations did not in cancer patients. Therefore, we suggest that the activated DCs shown here might be used as a basic element for the combinatorial cancer immunotherapy.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (8 results)

All 2006 2005

All Journal Article (8 results)

  • [Journal Article] Successful tumor eradication was achieved by collaboration of augmented cytotoxic activity and anti-angiogenic effects following therapeutic vaccines containing helper-activating analog-loaded DCs and tumor antigen DNA2006

    • Author(s)
      Teramoto K, Kontani K, Fujita T, Sawai S, Tezuka N, Fujino S
    • Journal Title

      Cancer Immunol. Immunother. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Spontaneous elicitation of potent anti-tumor immunity and eradication of established tumors by administration of DNA encoding soluble transforming growth factor-beta II receptor without active antigen-sensitization2006

    • Author(s)
      Kontani K, Fujita T, Sawai S, Tezuka N, Fujino S., Yamauchi A, Yokomise H
    • Journal Title

      Cancer Immunol. Immunother. 55

      Pages: 579-587

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Successful tumor eradication was achieved by collaboration of augmented cytotoxic activity and anti-angiogenic effects following therapeutic vaccines containing helper-activating analog-loaded DCs and tumor antigen DNA2006

    • Author(s)
      Teramoto K, Kontani K, Fujita T, Sawai S, Tezuka N, Fujino S.
    • Journal Title

      Cancer Immunol. Immunother. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Spontaneous elicitation of potent anti-tumor immunity and eradication of established tumors by administration of DNA encoding soluble transforming growth factor-beta II receptor without active antigen-sensitization2006

    • Author(s)
      Kontani K, Fujita T, Sawai S, Tezuka N, Fujino S.Yamauchi A, Yokomise H.
    • Journal Title

      Cancer Immunol. Immunother. 55

      Pages: 579-587

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Successful tumor eradication was achieved by collaboration of augmented cytotoxic activity and anti-angiogenic effects following therapeutic vaccines containing helper-activating analog-loaded dendritic cells and tumor antigen DNA2006

    • Author(s)
      Teramoto K, Kontani K, Fujita T, Sawai S, Tezuka N, Fujino S
    • Journal Title

      Cancer Immunol.Immunother. 56

      Pages: 331-342

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Galectin-9 induces maturation of human monocyte-derived dendritic cells2005

    • Author(s)
      Dai SY, Kontani K, Yamauchi A, Hirashima M
    • Journal Title

      J. Immunol. 175

      Pages: 2974-2981

    • NAID

      10020414811

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Galectin-9 induces maturation of human monocyte-derived dendritic cells2005

    • Author(s)
      Dai SY, Kontani K, Yamauchi A, Hirashima M.
    • Journal Title

      J. Immunol. 175

      Pages: 2974-2981

    • NAID

      10020414811

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 転移再発癌患者からの活性型成熟樹状細胞誘導法2005

    • Author(s)
      紺谷桂一, 小笠原一誠
    • Journal Title

      Biotherapy 19

      Pages: 339-346

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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