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Efficient Induction of HTLV-1-specific CTL by HTLV-1/HBc Chimeric Particle without Adjuvant as a Prophylactic for HTLV-1-associated T-cell Leukemia

Research Project

Project/Area Number 19790671
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionFukuoka University (2008)
Kagoshima University (2007)

Principal Investigator

KOZAKO Tomohiro  Fukuoka University, 薬学部, 助教 (40398300)

Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥1,840,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥240,000)
Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥800,000 (Direct Cost: ¥800,000)
Keywords免疫制御学 / 免疫療法 / HTLV-1 / ATL / CTL / ワクチン / HLA / 腫瘍免疫
Research Abstract

成人T細胞白血病(ArL)の原因ウイルス(HTLv-1)に特異的なcTLの誘導を抗腫瘍免疫療法のモデルとして、効率的なHTLV-1特異的CTLの誘導法をin vivo及びin vitroにおいて解析した。Hepatitis B core(HBc)粒子にHLA-A*0201が認識するHTLV-l Taxエピトープを挿入したHTLV-1/HBcキメラ粒子を作製した後、HLA-A*0201改変トランスジェニックマウスに本キメラ粒子を免疫し、その免疫原性を検討した。本粒子免疫群においてHTLV-1特異的なIFN-γ反応がみられ、テトラマー法によりHTLV-1特異的CD8陽性細胞が確認できた。またマウス骨髄樹状細胞と本粒子を共培養した結果、CD86、HLA-A*02、MHCクラス2、TLR4分子の発現が有意に増加した。これらの結果より、粒子のヘルパー活性によりアジュバント無しで樹状細胞の成熟化が促進し効率的CTL誘導能を有する可能性が示唆された。本研究により、免疫細胞療法によるHTLv-1特異的cTLの誘導を目的とするATL発症予防・治療のための免疫療法の臨床応用への基盤が確立できた。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (30 results)

All 2009 2008 2007 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (21 results) Remarks (1 results)

  • [Journal Article] PD-1/PD-L1 e xpression in HTLV-1 carriers and adult T-cell leuk emia/lymphoma patients.2009

    • Author(s)
      Kozako T., Yoshimitsu M., et al.
    • Journal Title

      Leukemia 23

      Pages: 75-382

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] PD-1/PD-L1 expression in HTLV-1 carriers and adult T-cell leukemia/lymphoma patients2009

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

      Leukemia 23

      Pages: 375-382

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-apoptotic roles of PAI-1 as a neurotrophic factor in the central nervous system.2008

    • Author(s)
      Soeda S., Koyanagi S., Yukako K., KozakoT., et al.
    • Journal Title

      Thrombosis and Haemostasis 100

      Pages: 1014-1020

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] CTL exhaustion in persistent HTLV-1 infection and ATLL is rest ored through PD-1/PD-L1 pathwa2008

    • Author(s)
      Kozako T., Yoshimitsu M., et al.
    • Journal Title

      Blood 110

      Pages: 511-511

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-apoptotic roles of PAI-1 as a neurotrophic factor in the central nervous system2008

    • Author(s)
      Soeda S., et.al.
    • Journal Title

      Thrombosis and Haemostasis 100

      Pages: 1014-1020

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-HTLV-1 Taxantibody and Tax-specific cytotoxic T lymphocyte are associated with a reduction in HTLV-1 proviral load in asymptomatic carriers.2007

    • Author(s)
      Akimoto M, Kozako T, et al.
    • Journal Title

      Journal of Medical Virology 79

      Pages: 977-986

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-HTLV-1 Tax antibody and Tax-specific cytotoxic T lymphocyte are associated with a reduction in HTLV-1 proviral load in asymptomatic carriers2007

    • Author(s)
      Akimoto M, Kozako T, et. al.
    • Journal Title

      Journal of Medical Virology 79

      Pages: 977-986

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CTL exhaustion in persistent HTLV-1 infection and ATLL is restored through PD-1/PD-L1 pathway2007

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

      Blood 110

      Pages: 511-511

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Efficient Induction of HTLV-1-specific CTL by HTLV-1/HBc Chimeric Particle without Adjuvant as a Prophylactic for HTLV-1-associated T-cell Leukemia2008

    • Author(s)
      Kozako T., et.al.
    • Organizer
      The American Society of Hematology 50th Annual Meeting
    • Place of Presentation
      San Francisco, CA
    • Year and Date
      2008-12-07
    • Related Report
      2008 Annual Research Report
  • [Presentation] Immunological Function against Human T-lymphotrophic virus type I in Carriers with Collagen Diseases and HAM/TSP2008

    • Author(s)
      Kozako T., et.al.
    • Organizer
      The American Society of Hematology 50th Annual Meeting
    • Place of Presentation
      San Francisco, CA
    • Year and Date
      2008-12-07
    • Related Report
      2008 Annual Research Report
  • [Presentation] Efficient Induction of HTLV-1-specific CTL by HTLV-1/HBc Chimeric Particle without Adjuvant as a Prophylactic for HTLV-1-associated T-cell Leukemia.2008

    • Author(s)
      Kozako T., Fukada K., et al.
    • Organizer
      The American Society of Hematology 50th Annual Meeting
    • Place of Presentation
      San Francisco、CA
    • Year and Date
      2008-12-06
    • Related Report
      2008 Final Research Report
  • [Presentation] Immunological Function against Human T-lymphotrophic virus type I in Carriers with Collagen Diseases and HAM/TSP.2008

    • Author(s)
      Kozako T., Yoshimitsu M., et al.
    • Organizer
      he American Society of Hematology 50th Annual Meeting
    • Place of Presentation
      San Francisco, CA
    • Year and Date
      2008-12-06
    • Related Report
      2008 Final Research Report
  • [Presentation] TLV-1/HBcキメラ粒子による効率的HTLV-1特異的CTL誘導法2008

    • Author(s)
      小迫知弘、平田真哉ら
    • Organizer
      第67回日本癌学会総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2008-10-28
    • Related Report
      2008 Final Research Report
  • [Presentation] HTLV-1/HBcキメラ粒子による効率的HTLV-1特異的CTL誘導法2008

    • Author(s)
      小迫知弘ら
    • Organizer
      第67回日本癌学会総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] HTLV」1特異的CTL疲弊におけるPD-1/PD-Ll経路の関与2008

    • Author(s)
      小迫知弘、吉満誠ら
    • Organizer
      第1回HTLV-1研究会
    • Place of Presentation
      東京都
    • Year and Date
      2008-08-23
    • Related Report
      2008 Final Research Report
  • [Presentation] HTLV-1特異的CTL疲弊におけるPD-1/PD-L1経路の関与2008

    • Author(s)
      小迫知弘ら
    • Organizer
      第1回HTLV-1研究会
    • Place of Presentation
      東京都
    • Year and Date
      2008-08-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] 無症候性HTLV-1キャリアとHTLV-1感染膠原病患者におけるHTLV-1特異的細胞傷害性T細胞認識エピトープの比較2008

    • Author(s)
      秋元正樹、小迫知弘ら
    • Organizer
      第53回日本リウマチ学会総会・学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2008-04-05
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] ATLLにみられるHTLV-1特異的CTLの機能不全におけるPD-1/PD-Ll経路の関与2007

    • Author(s)
      小迫知弘、吉満誠ら
    • Organizer
      第1回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      東京都
    • Year and Date
      2007-12-15
    • Related Report
      2008 Final Research Report
  • [Presentation] ATLLにみられるHTLV-1特異的CTLの機能不全におけるPD-1/PD-L1経路の関与2007

    • Author(s)
      小迫知弘、吉満誠, ら
    • Organizer
      第1回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      東京都
    • Year and Date
      2007-12-15
    • Related Report
      2007 Annual Research Report
  • [Presentation] CTL exhaustion in persistent HTLV-1 infection and ATLL is restored through PD-1/PD-L1 pathway.2007

    • Author(s)
      Kozako, T., Yoshimitsu, M., et al.
    • Organizer
      The American Society of Hematology 49th Annual Meeting
    • Place of Presentation
      Atlanta, Georgia
    • Year and Date
      2007-12-08
    • Related Report
      2008 Final Research Report
  • [Presentation] CTL exhaustion in persistent HTLV-1 infection and ATLL is restored through PD-1/PD-L1 pathway2007

    • Author(s)
      Kozako. T., Yoshimitsu, M., et. al.
    • Organizer
      The American Society of Hematology 49th Annual Meeting
    • Place of Presentation
      Atlanta, Georgia
    • Year and Date
      2007-12-08
    • Related Report
      2007 Annual Research Report
  • [Presentation] 膠原病合併HTLV-1キャリアにおいて特異的CTLが認識するHTLV-1エピトープの解析2007

    • Author(s)
      北國うらら、小迫知弘ら
    • Organizer
      第24回日本薬学会九州支部大会
    • Place of Presentation
      福岡市
    • Year and Date
      2007-12-07
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] 成人T細胞白血病リンパ腫におけるPD-1/PD-L1経路の関与の検討2007

    • Author(s)
      吉満誠、小迫知弘ら
    • Organizer
      第69回日本血液学会総会・第49回日本臨床血液学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2007-10-10
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] Exhaustion of HTLV-1 Tax specific CTL in HTLV-1 carriers and adult T cell leukemia patients by PD-1/PD-L1 pathway2007

    • Author(s)
      小迫知弘、有馬直道
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2007-10-04
    • Related Report
      2007 Annual Research Report
  • [Presentation] Exhaustion of HTLV-lTax specific CTL in HTLV-1 carriers and adultTcellleukemiapatientsbyPD-1/PD-Llpathway2007

    • Author(s)
      小迫知弘、有馬直道
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2007-10-03
    • Related Report
      2008 Final Research Report
  • [Presentation] Deficiency of CTL function in adult T-cell leukemia patientsmediated by interaction of PD-l and PD-Ll2007

    • Author(s)
      Kozako,T.,Ybshimitsu,M.,etal
    • Organizer
      13th International Confbrence of Human Retrovivology
    • Place of Presentation
      Hakone, Japan
    • Year and Date
      2007-05-22
    • Related Report
      2008 Final Research Report
  • [Presentation] SerumAnti-Tax Antibody Correalates to Lowere Neutrophil Counts in Patientes with HTLV-lInfection.2007

    • Author(s)
      Hamada, H., Matsushita, K., Akimoto, M., Arima, N., Sawada, T., Kozako, T.,etal.
    • Organizer
      13th International Confbrence of Human Retrovivology
    • Place of Presentation
      HTLV Hakone,Japan
    • Year and Date
      2007-05-22
    • Related Report
      2008 Final Research Report
  • [Presentation] Deficiency of CTL function in adult T-cell leukemia patients mediated by interaction of PD-1 and PD-L12007

    • Author(s)
      Kozako. T. Yoshimitsu, M., et. al.
    • Organizer
      13th International Conference of Human Retrovivology; HTLV
    • Place of Presentation
      Hakone, Japan
    • Year and Date
      2007-05-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] Serum Anti-Tax Antibody Correalates to Lowere Neutrophil Counts in Patientes with HTLV-1 Infection.2007

    • Author(s)
      Hamada, H., Matsushita, K., Akimoto, M., Arima, N., Sawada, T., Kozako, T., et. al.
    • Organizer
      13th International Conference of Human Retrovivology; HTLV
    • Place of Presentation
      Hakone, Japan
    • Year and Date
      2007-05-22
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.kufm.kagoshima-u.ac.jp/~k-blood/

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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