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Development of HTLV-I-specific anti-cancer therapy by using single chain T cell receptors and single chain trimers of MHC-I.

Research Project

Project/Area Number 24590547
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionHokkaido University

Principal Investigator

OHASHI Takashi  北海道大学, 遺伝子病制御研究所, 准教授 (10282774)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsHTLV-I / 成人T細胞白血病 / 動物モデル / 免疫治療 / ウイルス療法 / ATL / Tax / CTL / T細胞受容体 / single chain trimer / MHC-I / Single chain trimer
Outline of Final Research Achievements

The potential for novel therapies against Human T-cell leukemia virus type I (HTLV-I) induced-adult T-cell leukemia (ATL) has been assessed in an originally developed rat model of HTLV-I infection. The results indicate that combined treatment with m8Δ/RT1AlSCTax180L, which can express a single chain trimer of rat MHC-I with a Tax-epitope, and the epitope-specific CTL line, 4O1/C8, increased the cytolysis of FPM1V.EFGFP/8R cells, a CTL-resistant subclone of HTLV-I-infected FPM1 cells, compared with that using 4O1/C8 and m8Δ presenting an unrelated peptide, suggesting that the activation of 4O1/C8 by m8Δ/RT1AlSCTax180L further enhanced the killing of the HTLV-I-infected cells. Our results indicate that combined therapy of oncolytic m8Δ/RT1AlSCTax180L, and HTLV-I-specific CTLs may be effective for eradication of HTLV-I-infected cells, which evade from CTL lysis and potentially develop ATL. The present results should be useful for further verifying the strategies to fight against ATL.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (6 results)

All 2014 2012 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) Remarks (2 results)

  • [Journal Article] Effects of different promoters on the virulence and immunogenicity of a HIV-1 Env-expressing recombinant vaccinia vaccine.2014

    • Author(s)
      Isshiki M, Zhang X, Sato H, Ohashi T, Inoue M, and Shida H.
    • Journal Title

      Vaccine

      Volume: 32 Issue: 7 Pages: 839-845

    • DOI

      10.1016/j.vaccine.2013.12.022

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Combined Cytolytic Effects of a Vaccinia Virus Encoding a Single Chain Trimer of MHC-I with a Tax-Epitope and Tax-Specific CTLs on HTLV-I-Infected Cells in a Rat Model2014

    • Author(s)
      Ohashi T, Nakamura T, Kidokoro M, Zhang X, Shida H
    • Journal Title

      BioMed Research International.

      Volume: 2014 Pages: 902478-902478

    • DOI

      10.1155/2014/902478

    • NAID

      120005434503

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elicitation of both anti HIV-1 env humoral and cellular immunities by replication vaccinia prime sendai virus boost regimen and boosting by CD40Lm2012

    • Author(s)
      Zhang X
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 12 Pages: 1-11

    • DOI

      10.1371/journal.pone.0051633

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] HTLV-Iに感染したTax特異的CTL細胞株の性状解析2012

    • Author(s)
      大橋 貴、田中勇悦、志田壽利
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪国際会議場 ( 大阪府 )
    • Related Report
      2012 Research-status Report
  • [Remarks] 北海道大学遺伝子病制御研究所感染病態分野

    • URL

      http://www.igm.hokudai.ac.jp/molvir/B4489149-53E3-4C68-AE87-9D7AD29B0841/894F0691-7651-491D-8350-0710C44103A3.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 感染病態トップページ

    • URL

      http://www.igm.hokudai.ac.jp/molvir/B4489149-53E3-4C68-AE87-9D7AD29B0841/894F0691-7651-491D-8350-0710C44103A3.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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