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 Fiscal Year Final Research Report

• Project/Area Number: 19790671
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Fukuoka University (2008); Kagoshima University (2007)
• Principal Investigator: KOZAKO Tomohiro Fukuoka University, 薬学部, 助教 (40398300)
• Project Period (FY): 2007 – 2008
• Keywords: 免疫制御学 / 免疫療法

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。

Research Products

• [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
  • 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
  • Peer Reviewed
• [Journal Article] CTL exhaustion in persistent HTLV-1 infection and ATLL is rest ored through PD-1/PD-L1 pathwa (2008)
  • Author(s): Kozako T., Yoshimitsu M., et al.
  • Journal Title: Blood 110 Pages: 511
  • 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
  • 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 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Exhaustion of HTLV-lTax specific CTL in HTLV-1 carriers and adultTcellleukemiapatientsbyPD-1/PD-Llpathway (2007)
  • 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
• [Presentation] Deficiency of CTL function in adult T-cell leukemia patientsmediated by interaction of PD-l and PD-Ll (2007)
  • 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
• [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