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An experimental study on cancer vaccine therapy using dendritic cells genetically transduced with the tumor antigen gene and the ubiquitin gene

Research Project

Project/Area Number 17591342
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionWakayama Medical University

Principal Investigator

NAKAMURA Masaki  Wakayama Medical University, School of Medicine, Second Department of Surgery, Assistant (80364090)

Co-Investigator(Kenkyū-buntansha) YAMAUE Hiroki  Wakayama Medical University, School of Medicine, Second Department of Surgery, Professor (20191190)
IWAHASHI Makoto  Wakayama Medical University, School of Medicine, Second Department of Surgery, Instructor (70244738)
HOTTA Tsukasa  Wakayama Medical University, School of Medicine, Second Department of Surgery, Instructor (50244744)
MATSUDA Kenji  Wakayama Medical University, School of Medicine, Second Department of Surgery, Assistant (30398458)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,880,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsDendritic cells (DCs) / CEA / Adnovirus vector / Ubiquitin / アデノウイルベクター
Research Abstract

Cancer immunotherapy using dendritic cells (DCs) adenovirally transduced with the whole tumor-associated antigen (TAA) gene is an effective approach. In this study, we established the carcinoembryonic antigen (CEA) -specific cytotoxic T lymphocytes (CTLs) using an in vitro stimulation with adenovirally modified human DCs that express CEA. Moreover, DCs were transduced with the fusion gene of the CEA gene and the ubiquitin gene, and we showed the more potent cytotoxic activity against CEA-expressing targets (A24). Streptococcal preparation OK-432 is useful for stimulating DCs in terms of the maturation. To augment therapeutic antitumor effect, we investigated whether the OK-432 stimulation would be more effective on inducing CEA-specific CTLs compared with the other typical stimuli. DCs were cultured under various conditions, tumor necrosis factor (TNF) -a, lipopolysaccharide (LPS) or OK-432. A cytotoxic assay using peripheral blood mononuclear cells (PBMCs) -derived CTLs was performed in a 4h^<-51>Cr release assay. OK-432 stimulated immature DCs to acquire mature phenotype and to produce significant amounts of T-helper 1 cytokines. In all groups (immature DCs, TNF-a/DCs, LPS/DCs, OK-432/DCs), CEA-specific CTLs were generated. OK-432-stimulated DCs (HLA-A24) induced the most potent cytotoxic activity against CEA-expressing targets (A24), and not against controls. OK-432/DCs could induce markedly potent CTLs specific to the target cells pulsed with CEA652 peptide (HLA-A24-restricted peptide), although others failed to induce potent CTLs. In conclusion, the CTLs induction protocol using adenovirally modified DCs transduced with the fusion gene of the CEA gene and the ubiquitin gene or after maturation with OK-432 showed a potent antitumor activity against CEA-expressing target cells, and is therefore promising for clinical applications as a cancer vaccine therapy.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (28 results)

All 2008 2007 2006 2005

All Journal Article (23 results) (of which Peer Reviewed: 10 results) Presentation (5 results)

  • [Journal Article] Streptococcal preparation OK-432 promotes the capacity of dendritic cells(DCs)to prime carcinoembryonic antigen(CEA)-specific cytotoxic T lymphocyte responses induced with genetically modified DCs that express CEA2008

    • Author(s)
      Ojima Toshiyasu
    • Journal Title

      Int J Oncol 32(2)

      Pages: 459-466

    • 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] Tumor vaccine therapy against recrudescent tumor using dendritic cells simultaneo usly transfected with tumor RNA and granulocyte macrophage colony-stimulating factor RNA2008

    • Author(s)
      Naka Teiji
    • Journal Title

      Cancer Sci 99(2)

      Pages: 407-413

    • 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] Streptococcal preparation OK-432 promotes the capacity of dendritic cells(DCs) to prime carcinoembryonic antigen(CEA)-specific cytotoxic T lymphocyte responses induced with genetically modified DCs that express CEA2008

    • Author(s)
      Ojima T, et. al.
    • Journal Title

      Int J Oncol 32(2)

      Pages: 459-466

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Tumor vaccine therapy against recrudescent tumor using dendritic cellsimultaneously transfected with tumor RNA and granulocyte macrophage colony-stimulating factor RNA2008

    • Author(s)
      Naka T, et. al.
    • Journal Title

      Cancer Sci 99(2)

      Pages: 407-413

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Tumor vaccine therapy against recrudescent tumor using dendritic cells simultaneously transfected with tumor RNA and granulocyte macrophage colony-stimulating factor RNA.2008

    • Author(s)
      Naka Teiji
    • Journal Title

      Cancer Sci 99(2)

      Pages: 407-413

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Streptococcal preparation OK-432 promotes the capacity of dendritic cells(DCs)to prime carcinoembryonic antigen(CEA)-specific cytotoxic T lymphocyte responses induced with genetically modified DCs that express CEA.2008

    • Author(s)
      Ojima Toshiyasu
    • Journal Title

      Int J Oncol 32(2)

      Pages: 459-466

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells.2008

    • Author(s)
      Ojima Toshiyasu
    • Journal Title

      Int J Oncol 31(4)

      Pages: 931-939

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells2007

    • Author(s)
      Ojima Toshiyasu
    • Journal Title

      Int J Oncol 31(4)

      Pages: 931-939

    • 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] Successful cancer vaccine therapy for carcinoembryonic antigen(CEA)-expressing colon cancer using genetically modified dendritic cells that express CEA and Thelper-type1 cytokines in CEA transgenic mice2007

    • Author(s)
      Ojima Toshiyasu
    • Journal Title

      Int J Cancer 120(3)

      Pages: 585-93

    • 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] Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells2007

    • Author(s)
      Ojima T, et. al.
    • Journal Title

      Int J Oncol 31(4)

      Pages: 931-939

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Successful cancer vaccine therapy for carcinoembryonic antigen(CEA)-expressing colon cancer using genetically modified dendritic cells that express CEA and T helper-type 1 cytokines in CEA transgenic mice2007

    • Author(s)
      Ojima T, et. al.
    • Journal Title

      Int J Cancer 120(3)

      Pages: 585-593

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Successful cancer vaccine therapy for carcinoembryonic antigen (CEA) -expressing colon cancer using genetically modified dendritic cells that express CEA and Thelper-type 1 cytokines in CEA transgenic mice2007

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

      Int J Cancer 120(3)

      Pages: 585-93

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The boosting effect of co-transduction with cytokine genes on cancer vaccine the rapy using genetically modified dendrite cells expressing tumor-associated antigen2006

    • Author(s)
      Ojima Toshiyasu
    • Journal Title

      Int J Oncol 28(4)

      Pages: 947-53

    • 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] Surgical management of small gastrointestinal stromal tumors of the stomach2006

    • Author(s)
      Iwahashi Makoto
    • Journal Title

      World J Surg 30(1)

      Pages: 28-35

    • 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] The boosting effect of co-transduction with cytokine genes on cancer vaccine therapy using genetically modified dendrite cells expressing tumor-associated antigen2006

    • Author(s)
      Ojima T, et. al.
    • Journal Title

      Int J Oncol 28(4)

      Pages: 947-953

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Surgical management of small gastrointestinal stromal tumors of the stomach2006

    • Author(s)
      Iwahashi M, et. al.
    • Journal Title

      World J Surg 30(1)

      Pages: 28-35

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Clinical impact of adjuvant chemotherapy on patients with stage III colorectal cancer : 1-LV/5FU chemotherapy as a modified RPMI regimen is an independent prognostic factor for survuval2006

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

      Anticancer Res 26(2B)

      Pages: 1425-32

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The boosting effect of co-transduction with cytokine genes on cancer vaccine therapy using genetically modified dendrite cells expressing tumor-associated antigen.2006

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

      Int J Oncol 28(4)

      Pages: 947-953

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Dendritic cells transduced with tumor-associated antigen gene elicit potent therape utic antitumor immunity: comparison with immunodorninant peptide-pulsed DCs2005

    • Author(s)
      Nakamura M
    • Journal Title

      Oncology 68(2-3)

      Pages: 163-70

    • 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] Dendritic cells transduced with tumor-associated antigen gene elicit potent therapeutic antitumor immunity : comparison with immunodominant peptide-pulsed DCs2005

    • Author(s)
      Nakamura M, et. al.
    • Journal Title

      Oncology 68(2-3)

      Pages: 163-170

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Dendritic cells transduced with tumor-associated antigen gene elicit potent therapeutic antitumor immunity : comparison with immunodominant peptide-pulsed DCs.2005

    • Author(s)
      Nakamura M et al.
    • Journal Title

      Oncology 68(2-3)

      Pages: 163-170

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Individualized adjuvant chemotherapy guided by chemosensitivity test sequential to extended surgery for advanced gastric cancer.2005

    • Author(s)
      Iwahashi M et al.
    • Journal Title

      Anticancer Res 25(5)

      Pages: 3453-3459

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Evaluation of chemosensitivity testing with highly purified tumor cells in 435 patients with gasytric cancer using an MTT assay.2005

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

      Anticancer Res 25(2A)

      Pages: 931-937

    • Related Report
      2005 Annual Research Report
  • [Presentation] 膵IPMN由来浸潤癌におけるMSLNの発現形式2007

    • Author(s)
      宮澤 基樹
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-04
    • Related Report
      2007 Annual Research Report
  • [Presentation] 膵IPMN由来浸潤癌におけるMSLNの発現形式2007

    • Author(s)
      宮澤 基樹
    • Organizer
      日本消化器外科学会
    • Place of Presentation
      東京
    • Year and Date
      2007-07-19
    • Related Report
      2007 Annual Research Report
  • [Presentation] 膵IPMN由来浸潤癌におけるMSLNの発現形式2007

    • Author(s)
      宮澤 基樹
    • Organizer
      日本膵臓学会
    • Place of Presentation
      福岡
    • Year and Date
      2007-06-28
    • Related Report
      2007 Annual Research Report
  • [Presentation] OK-432 promotes the capacity of DCs to prime TAA-specific CTLs induced with genetically modified DCs expressing TAA2007

    • Author(s)
      Toshiyasu Ojima
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] OK-432 promotes the capacity of DCs to prime TAA-specific CTLs induced with genetically modified DCs expressing TAA2007

    • Author(s)
      Ojima T, et. al.
    • Organizer
      66 Japanese Cancer Association
    • Place of Presentation
      Ynknhama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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

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