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Characterization of HBZ specific T cells for new anti-HTLV-1 therapy

Research Project

Project/Area Number 26860301
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Virology
Research InstitutionKyoto University

Principal Investigator

SUGATA Kenji  京都大学, ウイルス研究所, 研究員 (10650616)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsHTLV-1 / 成人T細胞白血病 / HBZ / 細胞障害性T細胞 / 遺伝子組換えワクシニアウイルス / HBZ特異的CTL / ワクチン
Outline of Final Research Achievements

HTLV bZIP factor (HBZ) is consistently expressed in HTLV-1 infected cells and ATL cells. Therefore, HBZ is a potential therapeutic target for immunotherapy of HTLV-1 related diseases and adult T cell leukemia (ATL). In this study, we generated and characterized HBZ-specific CTLs using HBZ-expressing recombinant vaccine virus (rVV-HBZ). HBZ-specific CTLs were induced in rVV-HBZ immunized mice (C57BL/6) and produced effector cytokines (IFN-γ and TNF-α) by HBZ peptide stimulation. HBZ specific T cell response was also observed in rVV-HBZ-immunized Rhesus macaque. These HBZ-specific CTLs were produced effector cytokines by HBZ157-176 peptide stimulation. Furthermore we generated human HBZ specific CTLs from HLA-A2 and HLA-A24 positive healthy donor using HBZ157-176 peptide. The HBZ specific CTLs produce effector cytokines when stimulated with HBZ157-176 peptide-pulsed BLCL. This study suggests that HBZ specific CTLs could be useful for ATL treatment.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (7 results)

All 2016 2015 2014

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] HTLV-1 bZIP Factor Impairs Anti-viral Immunity by Inducing Co-inhibitory Molecule, T cell Immunoglobulin and ITIM Domain (TIGIT).2016

    • Author(s)
      Yasuma K, Yasunaga JI, Takemoto K, Sugata K, Takenouchi N, Nakagawa M, Suzuki Y, and Matsuoka M.
    • Journal Title

      PLoS Pathogens

      Volume: 12 Issue: 1 Pages: e1005372-e1005372

    • DOI

      10.1371/journal.ppat.1005372

    • NAID

      120005763385

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Protective effect of cytotoxic T lymphocytes targeting HTLV-1 bZIP factor.2015

    • Author(s)
      Sugata K, Yasunaga JI, Mitobe Y, Miura M, Miyazato P, Kohara M, and Matsuoka M.
    • Journal Title

      Blood

      Volume: 126 Issue: 9 Pages: 1095-1105

    • DOI

      10.1182/blood-2015-04-641118

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HTLV-1感染の疫学と病原性発現機構2015

    • Author(s)
      菅田謙治、松岡雅雄
    • Journal Title

      日本臨床

      Volume: 1087 Pages: 49-54

    • Related Report
      2015 Annual Research Report
  • [Presentation] HBZはCCR4発現を誘導する2015

    • Author(s)
      菅田謙治、安永純一朗、古田梨愛、松岡雅雄
    • Organizer
      第2回日本HTLV-1学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-08-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Anti-CCR4 antibody activates virus-specific immune response in STLV-1 infected Japanese monkey2015

    • Author(s)
      Kenji Sugata, Junichirou Yasunaga, Kisato Nosaka and Masao Matsuoka
    • Organizer
      17th International Conference on Human Retrovirology : HTLV & Related Viruses
    • Place of Presentation
      France, Martinique
    • Year and Date
      2015-06-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Anti-CCR4抗体はTregと感染細胞を同時に標的にすることで、STLV-1自然感染ニホンザルでのウイルス特異的免疫反応を活性化させる2014

    • Author(s)
      菅田謙治, 安永純一朗, 三浦未知, 明里宏文, 小柳義夫, 小原道法, 松岡雅雄
    • Organizer
      日本ウイルス学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-11
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] HTLV-1関連疾患の予防及び/又は治療用ワクチン2014

    • Inventor(s)
      松岡雅雄・菅田謙治
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-07-31
    • Acquisition Date
      2016-03-10
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2017-05-10  

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