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Development of therapeutic hepatitis peptide vaccine using a novel T cell receptor cloning system

Research Project

Project/Area Number 24791019
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Infectious disease medicine
Research InstitutionUniversity of Toyama

Principal Investigator

KOBAYASHI Eiji  富山大学, 大学院医学薬学研究部(医学), 助教 (70459733)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsペプチドワクチン / T細胞受容体 / Cytotoxic T lymphocyte / C型肝炎ウイルス
Research Abstract

We have recently reported hTEC10 system (human TCR efficient cloning within 10 days) by which we can obtain TCR cDNAs from a single Ag-specific human T cell and determine their antigen specificity within 10 days. In this study, we applied this system to clone human Hepatitis C virus (HCV)-specific TCRs from patients with chronic hepatitis and compare affinities of cloned TCRs.
To this end, we first predicted HLA-A24-restricted candidate epitopes of HCV components (Core, E1, E2, P7, NS2, NS3, NS4, NS5A, NS5B) using BIMAS system, then stimulated peripheral blood lymphocytes (PBLs) from the 10 patients who had HLA-A24 allel with the candidate peptide mixtures. As a result, we detected activated CD8+ T cells from PBLs of 4 patients. We are going to clone TCRs of the CD8+ T cells and compare affinities of cloned TCRs.

Report

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

    (23 results)

All 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (12 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 2 results)

  • [Journal Article] A novel system for cloning human TCRs : Cutting short the way to TCR-based anticancer therapy2014

    • Author(s)
      Kobayashi E, Kishi H, Muraguchi A
    • Journal Title

      Oncoimmunology

      Volume: 3(1)

    • URL

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960297/

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Retroviral vectors for homologous recombination provide efficient cloning and expression in mammalian cells2014

    • Author(s)
      Kobayashi E, Kishi H, Ozawa T, Horii M, Hamana H, Nagai T, Muraguchi A
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 444 Issue: 3 Pages: 319-324

    • DOI

      10.1016/j.bbrc.2014.01.049

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A new cloning and expression system yields and validates TCRs from blood lymphocytes of patients with cancer within 10 days.2013

    • Author(s)
      Kobayashi E., et al
    • Journal Title

      Nature Medicne

      Volume: 19 Issue: 11 Pages: 1542-1546

    • DOI

      10.1038/nm.3358

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel rabbit immunospot array assay on a chip allows for the rapid generation of rabbit monoclonal antibodies with high affinity.2012

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

      PLoS One

      Volume: 7 Issue: 12 Pages: e52383-e52383

    • DOI

      10.1371/journal.pone.0052383

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Unbiased analysis of TCRα/β chains at the single-cell level in human CD8<sup>+</sup> T-cell subsets2012

    • Author(s)
      Sun X, Saito M, Sato Y, Chikata T, Naruto T, Ozawa T, Kobayashi E, Kishi H, Muraguchi A, Takiguchi M
    • Journal Title

      PLoS One

      Volume: 7 Issue: 7 Pages: e40386-e40386

    • DOI

      10.1371/journal.pone.0040386

    • URL

      https://pure.teikyo.jp/en/publications/4de66c37-9be7-48f7-8a21-dd8a125a0565

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The binding affinity of a soluble TCR-Fc fusion protein is significantly improved by crosslinkage with an anti-Cβ antibody2012

    • Author(s)
      Ozawa T ., Horii M., Kobayashi E., Jin A., Kishi H., and Muraguchi A
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 422 Issue: 2 Pages: 245-249

    • DOI

      10.1016/j.bbrc.2012.04.134

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Cloning and functional analysis of human telomerase reverse transcriptase (hTERT)-specific TCRs from peptide-vaccinated patients2013

    • Author(s)
      Eiji Kobayashi, Hidetoshi Nakagawa, Hiroshi Hamana, Hiroyuki Kishi, Tatsuhiko Ozawa, Aishun Jin and Atsushi Muraguchi
    • Organizer
      第42回日本免疫学会総会
    • Place of Presentation
      幕張
    • Year and Date
      2013-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] A novel cloning system of human antigen-specific TCRs can confer the candidates for cancer gene therapy2013

    • Author(s)
      E.kobayashi, Mizukoshi E., Kishi H., Hamana H., Nagai T., Ozawa T., Nakagawa H., Jin A., Kaneko S., and Muraguchi A
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-03
    • Related Report
      2013 Final Research Report
  • [Presentation] Cloning of human antigen-specific TCRs can confer the candidates for cancer gene therapy2013

    • Author(s)
      Eiji Kobayashi, Eishiro Mizukoshi, Hiroyuki Kishi, Hiroshi Hamana, Terumi Nagai, Tatsuhiko Ozawa , Hidetoshi Nakagawa, Aishun Jin, Shuichi Kaneko and Atsushi Muraguchi
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milan
    • Year and Date
      2013-08-22
    • Related Report
      2013 Final Research Report
  • [Presentation] A novel cloning system of human antigen-specific TCRs can confer the candidates for cancer gene therapy2013

    • Author(s)
      Eiji Kobayashi, Eishiro Mizukoshi, Hiroyuki Kishi, Tatsuhiko Ozawa, Hiroshi Hamana, Terumi Nagai, Hidetoshi Nakagawa, Aishun Jin, Shuichi Kaneko and Atsushi Muraguchi
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Cloning of human antigen-specific TCRs can confer the candidates for cancer gene therapy2013

    • Author(s)
      Eiji Kobayashi, Eishiro Mizukoshi, Hiroyuki Kishi, Hiroshi Hamana, Terumi Nagai, Tatsuhiko Ozawa ,Hidetoshi Nakagawa, Aishun Jin, Shuichi Kaneko and Atsushi Muraguchi
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Miilan, Italy
    • Related Report
      2013 Annual Research Report
  • [Presentation] マイクロウェルアレイチップを用いたウサギモノクローナル抗体の迅速作製法の開発2012

    • Author(s)
      小澤龍彦, 朴 秀虹, 小林栄治, 周越, 櫻井宏明, 安東嗣修, 金 艾順, 岸 裕幸, 村口 篤
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] Comparison of TCR repertoires in EBV-specific T cells detected by three different staining methods2012

    • Author(s)
      浜名 洋, 小林栄治, 岸 裕幸, 小澤龍彦, 金 艾順, 村口 篤
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2012-12-05
    • Related Report
      2013 Final Research Report
  • [Presentation] The binding affinity of a soluble TCR-Fc fusion protein is significantly improved by crosslinkage with an anti-Cβ antibody2012

    • Author(s)
      小澤龍彦, 小林栄治, 金 艾順, 岸裕幸, 村口 篤
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2012-12-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Detection of antigen-stimulated cytokine secretion in human T-cells at single cell levels on a live cell chip2012

    • Author(s)
      岸 裕幸, 金 艾順, 小林栄治, 小澤龍彦, 浜名 洋, 村口 篤
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2012-12-05
    • Related Report
      2013 Final Research Report
  • [Presentation] A novel human TCR efficient cloning system confers candidate for TCR gene therapy within 10 days2012

    • Author(s)
      E.kobayashi, Mizukoshi E., Kishi H., Hamana H., Nagai T., Ozawa T., Nakagawa H., Jin A., Kaneko S., and Muraguchi A
    • Organizer
      27th Annual Meeting of Society for Immunotherapy of Cancer
    • Place of Presentation
      North Bethesda
    • Year and Date
      2012-10-26
    • Related Report
      2013 Final Research Report
  • [Presentation] がんのTCR 遺伝子治療にむけた候補TCR 遺伝子の迅速クローニング法2012

    • Author(s)
      岸 裕幸, 小林栄治, 水腰英四郎, 小澤龍彦, 金子周一, 村口 篤
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 抗原特異的T 細胞受容体遺伝子の超迅速クローニングシステムの構築2012

    • Author(s)
      小林栄治, 水腰英四郎, 岸 裕幸, 小澤龍彦, 浜名 洋, 長井輝美, 金 艾順, 金子周一, 村口 篤
    • Organizer
      第16回日本がん免疫学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-07-26
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 抗原特異的T細胞受容体の取得方法2014

    • Inventor(s)
      小林栄治, 岸裕幸, 村口篤
    • Industrial Property Rights Holder
      国立大学法人富山大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-007576
    • Filing Date
      2014-01-20
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] T細胞受容体のクローニング方法2013

    • Inventor(s)
      村口篤, 岸裕幸, 小林栄治, 小澤龍彦
    • Industrial Property Rights Holder
      国立大学法人富山大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-07-24
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] T細胞の刺激方法およびその利用2013

    • Inventor(s)
      岸裕幸, 村口篤, 浜名洋, 小林栄治, 小澤龍彦
    • Industrial Property Rights Holder
      国立大学法人富山大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-03-06
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 外来遺伝子導入用ベクター及び外来遺伝子が導入されたベクターの製造方法2013

    • Inventor(s)
      堀井雅恵, 岸裕幸, 小林栄治, 小澤龍彦, 村口篤
    • Industrial Property Rights Holder
      国立大学法人富山大学
    • Industrial Property Rights Type
      特許
    • Acquisition Date
      2013-04-19
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] T細胞受容体のクローニング方法2012

    • Inventor(s)
      村口篤, 岸裕幸, 小林栄治, 小澤龍彦
    • Industrial Property Rights Holder
      国立大学法人富山大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-164442
    • Filing Date
      2012-07-25
    • Related Report
      2013 Final Research Report

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

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