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CHARACTERIZATION OF TCR Vβ REPERTOIRE AND TH1/TH2 CYTOKINE RELEASE OF TUMOR-SPECIFIC CYTOTOXIC T CELLS

Research Project

Project/Area Number 09671340
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionTOKYO WOMEN'S MEDICAL UNIVERSITY

Principal Investigator

ARUGA Atsushi  TOKYO WOMEN'S MEDICAL UNIVERSITY, DEPARTMENT OF GASTROENTEROLOGICAL SURGERY, ASSISTANT PROFESSOR, 医学部, 講師 (40221056)

Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsTCR Vβ / CTL / Dendritic cell / Cytokine / Immunotherapy / サイトカイン / 樹状細胞 / 抗原ペプチド / TCRVβ / 免疫療法
Research Abstract

In animal study, tumor-primed lymph node cells or splenocyte activated with tumor or anti-CD3 plus IL-2 mediated tumor regression in adoptive immunotherapy models and release tumor-reactive Type 1 cytokines in tumor specific manner. These cytotoxic T cells (CTL) consist of the several TCR Vβ subpopulations. The majority of the whole population were composed of Vβ3, 5, 7, 8 and 11+cells. TCR Vβ8+cells released high amounts of IFNγ with minimal amounts of IL-10 in response to tumor and mediated tumor regression in vivo. In contrast, TCR Vβ5, 7, 11+cells released low amounts of IFNγ with high level of IL-10 and had no in vivo antitumor reactivity. In human study, tumor-specific CTLs could be generated with tumor lysate or synthetic peptide-pulsed dendritic cells in vitro. These CTLs released high amount of IFNγ with minimal amounts of IL-10 and mediated tumor lysis in vitro cytotoxic assay. TCR Vβ usage of the patients with synthetic peptide-pulsed dendritic cell as cancer vaccine indicated the different profiles of TCR Vβ usage after vaccination. In this study, I demonstrated that Th1/Th2 cytokine patterns are expressed by immune T cells based upon TCR Vβ usage in mouse and human. Selective activation of effective Vβ subpopulation would be required for adoptive immunotherapy.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] 有賀淳: "MUC-1ペプチド提示樹状細胞を用いたCTLの誘導"Biotherapy. 13(5). 547-549 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 有賀淳: "樹状細胞を用いたヒト胃癌に対する特異的CTLの誘導"Biotherapy. 13(1). 105-107 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga: "Enhanced adjuvant effect of granulocyte-macrophage colony stimlating factor plus interleukin-12 compared with either alone in vaccine-induced tumor immunity."Cancer Gene Therapy. 6(1). 89-95 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 有賀淳: "樹状細胞を用いたCTLの抗腫瘍効果増強"Biotherapy. 12(5). 875-877 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga: "Type 1 versus Type 2 cytokine release by Vβ T cell subpopulations determine in vivo antitumor reactivity."Journal of Immunology. 159. 664-673 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga: "Reduced efficacy of allogeneic versus syngeneic fibroblasts modified to secrete cytolines as a tumor vaccine adjuvant."Cancer Research. 57. 3230-3237 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga: "Different cytokine profiles released by CD4+ and CD8+ tumor-draining lymph node cells involved in mediating tumor regression"Journal of Leukocyte Biology. 61. 507-516 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga, Keishi Tanigawa, Etsuko Aruga, Hua Yu, and Alfred E.Chang: "Enhanced adjuvant effect of granulocyte-macrophage colony stimulating factor plus interleukin-12 compared with either alone in vaccine-induced tumor immunity."Cancer Gene Therapy. 6(1). 89-95 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga, Yoshihito Kodera, Takashi Hatori, Takaji Furukawa, and Ken Takasaki: "Induction of MUC-1 specific CTL stimulated with peptide-pulsed dendritic cells."Biotherapy. 13(5). 547-549 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga, Yoshihito Kodera, Shingo Takeshita, Takaji Furukawa, and Ken Takasaki: "Induction of tumor-specific CTLs stimulated with tumor-pulsed dendritic cells in human gastric cancer."Biotherapy. 13(1). 105-107 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga, Shingo Takeshita, Takaji Furukawa, and Ken Takasaki: "Enhancement of in vitro cytolytic reactivity of T cells stimulated with tumor-pulsed dendritic cells."Biotherapy. 12(5). 875-877 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga, Etsuko Aruga, Keishi Tanigawa, D.Keith Bishop, Vernon K.Sondak, and Alfred E.Chang: "Type 1 versus Type 2 cytokine release by Vβ T cell subpopulations determines in vivo antitumor reactivity."J Immunology. 159. 664-673 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga, Etsuko Aruga, and Alfred E.Chang: "Reduced efficacy of allogeneic versus syngeneic fibroblasts modified to secrete cytokines as a tumor vaccine adjuvant."Cancer Research. 57. 3230-3237 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga, Etsuko Aruga, Mark J.Cameron, and Alfred E.Chang: "Different cytokine profiles released by CD4+ and CD8+ tumor-draining lymph node cells involved in mediating tumor regression."J Leukocyte Biology. 61. 507-516 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga, Koichi Shimizu, Keishi Tanigawa, Ken Takasaki: "Immunological and Clinical Response of Vaccination with synthetic MUC1 peptide-pulsed dendritic cells in patients with pancreatic cancer."Clinical Cancer Research. (submitted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga, Koichi Shimizu, Keishi Tanigawa, Ken Takasaki: "The Effect of Dendritic Cells In the generation of Tumor-specific Type1 cytotoxic T cells In the patients with B7-negative Hepatocellular carcinoma"Int J cancer. (submitted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Aruga, Koichi Shimizu, Keishi Tanigawa, Ken Takasaki: "TCR Vβ usage of antigen-specific CTLs generated with peptide-pulsed dendritic cells."J Immunology. (now preparing).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary

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Published: 1997-04-01   Modified: 2016-04-21  

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