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Development of cancer vaccine therapy targeting individual genetic mutations identified by next generation sequencing

Research Project

Project/Area Number 24659625
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Thoracic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

NAKAJIMA Jun  東京大学, 医学部附属病院, 教授 (90188954)

Co-Investigator(Kenkyū-buntansha) MURAKAWA Tomohiro  東京大学, 医学部附属病院, 講師 (50359626)
SANO Atsushi  東京大学, 医学部附属病院, 登録研究員 (20569834)
KAKIMI Kazuhiro  東京大学, 医学部附属病院, 特任教授 (80273358)
MATSUSHITA Hirokazu  東京大学, 医学部附属病院, 特任講師 (80597782)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺がん / 次世代シーケンス / 遺伝子変異 / MHCクラスI結合予測法 / 固有抗原 / 変異ペプチド / 免疫反応 / 個別化がん免疫治療 / 肺癌 / 膵臓癌 / 全エクソームシーケンス / 全RNAシーケンス / ミスセンス変異 / 膵がん / 全RNAシーケンス / RNAシーケンス / エクソームシーケンス
Outline of Final Research Achievements

We established the method to identify candidate unique antigens from cancer specific mutations in pancreatic cancer specimens by combining next generation sequencing with MHC class I binding algorism. We also developed an assay to verify immune responses against those candidate unique antigens in mice. In total 6 lung cancer patients consisting of 3 smokers and 3 non-smokers, the numbers of genetic mutations (missense mutations) were 280 on average in former versus 75 in latter. Accordingly, the numbers of candidate unique antigen-derived T cell epitopes predicted by the algorism were 535 on average in former versus 140 in latter. We successfully created the system predicting candidate unique antigens and verifying them, which is a prerequisite for individualized cancer immunotherapy development in lung cancer patients.

Report

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

    (22 results)

All 2015 2014 2013 Other

All Journal Article (11 results) (of which Peer Reviewed: 9 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Invited: 5 results) Remarks (3 results)

  • [Journal Article] γδ T cell therapy for the treatment of non-small cell lung cancer.2014

    • Author(s)
      Kakimi K, Matsushita H, Murakawa T, Nakajima J.
    • Journal Title

      Translational Lung Cancer Research

      Volume: 3 Pages: 23-33

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A pilot study of autologous tumor lysate-loaded dendritic cell vaccination combined with sunitinib for metastatic renal cell carcinoma2014

    • Author(s)
      Matsushita H, Enomoto Y, Kume H, Nakagawa T, Fukuhara H, Suzuki M, Fujimura T, Homma Y, Kakimi K.
    • Journal Title

      J Immunother Cancer.

      Volume: 2 Issue: 1 Pages: 30-30

    • DOI

      10.1186/s40425-014-0030-4

    • URL

      https://pure.teikyo.jp/en/publications/65394b91-7107-4d15-bb78-e05330dd78ff

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Intraperitoneal injection of in vitro expanded Vγ9Vδ2 T cells together with zoledronate for the treatment of malignant ascites due to gastric cancer.2014

    • Author(s)
      Wada I, Matsushita H, Noji S, Mori K, Yamashita H, Nomura S, Shimizu N, Seto Y, Kakimi K
    • Journal Title

      Cancer Med

      Volume: 3 Issue: 2 Pages: 362-375

    • DOI

      10.1002/cam4.196

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] γδ T cell therapy for the treatment of non-small cell lung cancer.2014

    • Author(s)
      Kakimi K, Matsushita H, Murakawa T, Nakajima J.
    • Journal Title

      Transl Lung Cancer Res

      Volume: 3 Pages: 23-33

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Adoptive cytotoxic T lymphocyte therapy triggers a counter-regulatory immunosuppressive mechanism via recruitment of myeloid-derived suppressor cells.2014

    • Author(s)
      Hosoi A, Matsushita H, Shimizu K, Fujii SI, Ueha S, Abe J, Kurachi M, Maekawa R, Matsushima K, Kakimi K.
    • Journal Title

      Int J Cancer.

      Volume: 134 Issue: 8 Pages: 1810-22

    • DOI

      10.1002/ijc.28506

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advances in the study of biomarkers of idiopathic pulmonary fibrosis in Japan2013

    • Author(s)
      Huang H1, Peng X, Nakajima J.
    • Journal Title

      BioScience Trends

      Volume: 7 Issue: 4 Pages: 172-177

    • DOI

      10.5582/bst.2013.v7.4.172

    • NAID

      130005054655

    • ISSN
      1881-7815, 1881-7823
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] High-grade Lung Adenocarcinoma With Fetal Lung-like Morphology: Clinicopathologic, Immunohistochemical, and Molecular Analyses of 17 Cases2013

    • Author(s)
      Morita S, Yoshida A, Goto A, Ota S, Tsuta K, Yokozawa K, Asamura H, Nakajima J, Takai D, Mori M, Oka T, Tamaru J, Itoyama S, Furuta K, Fukayama M, Tsuda H.
    • Journal Title

      Am J Surg Pathol

      Volume: 37(6) Issue: 6 Pages: 924-932

    • DOI

      10.1097/pas.0b013e31827e1e83

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer.2013

    • Author(s)
      Kawakami M, Morita S, Sunohara M, Amano Y, Ishikawa R, Watanabe K, Hamano E, Ohishi N, Nakajima J, Yatomi Y, Nagase T, Fukayama M, Takai D.
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 6 Pages: 598-612

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ex vivo characterization of γδ T-cell repertoire in patients after adoptive transfer of Vγ9Vδ2 T cells expressing the interleukin-2 receptor β-chain andthe common γ-chain.2013

    • Author(s)
      Izumi T, Kondo M, Takahashi T, Fujieda N, Kondo A, Tamura N, Murakawa T, Nakajima J, Matsushita H, Kakimi K.
    • Journal Title

      Cytotherapy

      Volume: 15(4) Issue: 4 Pages: 481-491

    • DOI

      10.1016/j.jcyt.2012.12.004

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] がん免疫編集機構における自然免疫系と適応免疫系の役割2013

    • Author(s)
      松下博和
    • Journal Title

      実験医学増刊2013

      Volume: 31 Pages: 92-99

    • Related Report
      2013 Research-status Report
  • [Journal Article] がん免疫編集機構2013

    • Author(s)
      松下博和
    • Journal Title

      医学のあゆみ

      Volume: 244 Pages: 739-744

    • Related Report
      2012 Research-status Report
  • [Presentation] 肺癌に対する免疫療法2015

    • Author(s)
      中島 淳
    • Organizer
      4月度 香川県内科医会呼吸器疾患談話会
    • Place of Presentation
      香川県社会福祉総合センター(香川県高松市番町)
    • Year and Date
      2015-04-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] CTL治療における腫瘍内免疫応答の解析2015

    • Author(s)
      垣見和宏
    • Organizer
      第12回日本免疫治療学研究会学術集会
    • Place of Presentation
      東京ガーデンパレス(東京都文京区)
    • Year and Date
      2015-02-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗mesothelin-キメラ型抗原受容体導入γδTリンパ球による免疫療法の有用性2014

    • Author(s)
      井上雄太、村山智紀、此枝千尋、一瀬淳二、日野春秋、長山和弘、松下博和、似鳥純一、安樂真樹、村川知弘、垣見和宏、中島淳
    • Organizer
      第55回日本肺癌学会定期学術集会
    • Place of Presentation
      国立京都国際会館(京都市左京区)
    • Year and Date
      2014-11-14 – 2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] γδT細胞を用いたがん免疫細胞治療におけるTIM-3とGalectin-9の相互作用2014

    • Author(s)
      神原佳織、藤枝奈緒、大平公亮、近藤篤、近藤真、泉謙道、高橋卓也、松下博和、和田郁雄、瀬戸泰之、垣見和宏
    • Organizer
      第18回日本がん免疫学会総会
    • Place of Presentation
      ひめぎんホール(愛媛県松山市)
    • Year and Date
      2014-07-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] Development of γδ T cell-based cancer immunotherapy2014

    • Author(s)
      垣見和宏
    • Organizer
      第18回日本がん免疫学会総会
    • Place of Presentation
      ひめぎんホール(愛媛県松山市)
    • Year and Date
      2014-07-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] がん免疫治療新時代に向けて2014

    • Author(s)
      垣見和宏
    • Organizer
      平成26年度沖縄県委託事業「先端医療産業開発拠点形成事業
    • Place of Presentation
      琉球大学(沖縄県中頭郡西原町)
    • Year and Date
      2014-05-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] クリニカルゲノミクスへの期待:がん免疫治療の見地から2013

    • Author(s)
      垣見 和宏
    • Organizer
      かずさDNA 研究所/産総研 生命情報工学研究センター共催ワークショップ
    • Place of Presentation
      東京都江東区産総研 臨海副都心センター 別館
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 癌免疫治療新時代に向けて2013

    • Author(s)
      垣見 和宏
    • Organizer
      第34回癌免疫外科研究会
    • Place of Presentation
      岡山県岡山市岡山プラザホテル
    • Related Report
      2013 Research-status Report
    • Invited
  • [Remarks] 東大病院呼吸器外科 ホームページ

    • URL

      http://cts.m.u-tokyo.ac.jp/thoracic-surgery

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京大学免疫細胞治療学講座ホームページ

    • URL

      http://immunoth.umin.jp/result/index_03.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京大学免疫細胞治療学(メディネット)ホームページ

    • URL

      http://immunoth.umin.jp/result/index_03.html

    • Related Report
      2013 Research-status Report

URL: 

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

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