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Identification of neoantigens and development of a novel personalized lung cancer treatment targeting passenger mutations

Research Project

Project/Area Number 26462124
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory surgery
Research InstitutionThe University of Tokyo

Principal Investigator

Nagayama Kazuhiro  東京大学, 医学部附属病院, 助教 (00647935)

Co-Investigator(Kenkyū-buntansha) 中島 淳  東京大学, 医学部附属病院, 教授 (90188954)
村川 知弘  東京大学, 医学部附属病院, 登録研究員 (50359626)
安樂 真樹  東京大学, 医学部附属病院, 特任准教授 (70598557)
似鳥 純一  東京大学, 医学部附属病院, 助教 (40424486)
北野 健太郎  東京大学, 医学部附属病院, 助教 (70647073)
垣見 和宏  東京大学, 医学部附属病院, 特任教授 (80273358)
松下 博和  東京大学, 医学部附属病院, 特任講師 (80597782)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺癌 / 遺伝子変異 / パッセンジャー変異 / neoantigen / 個別化医療 / 網羅的遺伝子解析 / エクソーム / トランスクリプトーム / ネオアンチゲン / 肺癌個別化医療 / 肺癌遺伝子変異の網羅的同定 / 変異検出パイプライン構築
Outline of Final Research Achievements

We developed algorithm to predict tumor specific antigens derive from somatic mutations, so called neoantigens, mostly from passenger mutations. We first identified somatic missense mutations in 6 primary lung cancer patients using multiple mutation-call softwares. Next, we added MHC binding prediction software and predicted candidate neoantigens in 15 lung cancer patients. Most of the predicted neoantigens derived from passenger mutations and were not shared among other patients. Finally, we combined transcriptome (RNAseq) data to exome-analysis pipeline to reduce false positives of expressed mutant mRNA. Thus, we developed efficient pipeline to target passenger mutation that could become candidate neoantigens using exome and RNAseq data.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (15 results)

All 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 3 results) Presentation (11 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Prediction and prioritization of neoantigens: integration of RNA sequencing data with whole-exome sequencing.2017

    • Author(s)
      Karasaki T, Nagayama K, Kuwano H, Nitadori JI, Sato M, Anraku M, Hosoi A, Matsushita H, Takazawa M, Ohara O, Nakajima J, Kakimi K.
    • Journal Title

      Cancer Sci.

      Volume: 108(2) Issue: 2 Pages: 170-177

    • DOI

      10.1111/cas.13131

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 総説 NeoantigensとWhole-Exome Sequencing2016

    • Author(s)
      唐崎隆弘、中島淳、垣見和宏
    • Journal Title

      癌と化学療法

      Volume: 43(7) Pages: 791-797

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Identification of Individual Cancer-Specific Somatic Mutations for Neoantigen-Based Immunotherapy of Lung Cancer.2016

    • Author(s)
      Karasaki T, Nagayama K, Kawashima M, Hiyama N, Murayama T, Kuwano H, Nitadori J, Anraku M, Sato M, Miyai M, Hosoi A, Matsushita H, Kikugawa S, Matoba R, Ohara O, Kakimi K, Nakajima J
    • Journal Title

      Journal of Thoracic Oncology

      Volume: 11(3) Issue: 3 Pages: 324-33

    • DOI

      10.1016/j.jtho.2015.11.006

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Detection and Tracking of NY-ESO-1-Specific CD8+ T Cells by High-Throughput T Cell Receptor β (TCRB) Gene Rearrangements Sequencing in a Peptide-Vaccinated Patient.2015

    • Author(s)
      Miyai M, Eikawa S, Hosoi A, Iino T, Matsushita H, Isobe M, Uenaka A, Udono H, Nakajima J, Nakayama E, Kakimi K.
    • Journal Title

      PLoS One

      Volume: 10(8) Issue: 8 Pages: e0136086-e0136086

    • DOI

      10.1371/journal.pone.0136086

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Immunogramを用いた肺癌治療の最適化2017

    • Author(s)
      唐崎隆弘、長山和弘、中島淳
    • Organizer
      第14回日本免疫治療学研究会学術集会
    • Place of Presentation
      東京都文京区
    • Year and Date
      2017-02-11
    • Related Report
      2016 Annual Research Report
  • [Presentation] イムノグラムを用いた肺癌に対する個別化治療戦略2016

    • Author(s)
      唐崎隆弘、長山和弘、垣見和宏、中島淳
    • Organizer
      第57回日本肺癌学会学術集会
    • Place of Presentation
      福岡県福岡市
    • Year and Date
      2016-12-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] Immunogram for Cancer-Immunity Cycle towards Personalized Immunotherapy of Lung Cancer2016

    • Author(s)
      Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
    • Organizer
      IASLC 17th World Conference on Lung Cancer
    • Place of Presentation
      Messe Wien Exhibition & Congress Center
    • Year and Date
      2016-12-07
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Concomitant driver mutation determines the tumor growth in EGFR mutation positive lung adenocarcinoma2016

    • Author(s)
      Kazuhiro Nagayama, Takahiro Karasaki, Hideki Kuwano, Jun-ichi Nitadori, Masaaki Sato, Masaki Anraku, Hirokazu Matsushita, Kazuhiro Kakimi, Jun Nakajima
    • Organizer
      IASLC 17th World Conference on Lung Cancer
    • Place of Presentation
      Messe Wien Exhibition & Congress Center
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肺癌におけるmutational/neoantigen burdenと免疫チェックポイント、immune signatureに関する検討2016

    • Author(s)
      唐崎隆弘、長山和弘、垣見和宏、中島淳
    • Organizer
      第33回日本呼吸器外科学会総会
    • Place of Presentation
      京都府京都市
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] 腫瘍特異的遺伝子変異抗原(Neoantigen)を標的としたがん免疫治療2016

    • Author(s)
      垣見和宏
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 肺癌におけるneoantigen load、免疫チェックポイント、およびimmune signatureに関する検討2016

    • Author(s)
      唐崎 隆弘、長山 和弘、中島 淳
    • Organizer
      第13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ホテル(東京都文京区)
    • Year and Date
      2016-02-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 新生抗原をターゲットにしたがん免疫治療法の開発2016

    • Author(s)
      松下博和、垣見和宏
    • Organizer
      第13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ホテル(東京都文京区)
    • Year and Date
      2016-02-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 既存のデータベースから抽出した遺伝子変異をターゲットとした肺癌ペプチドワクチン開発の限界について2015

    • Author(s)
      唐崎隆弘,長山 和弘,桑野 秀規,似鳥 純一,安樂 真樹,佐藤 雅昭,垣見 和宏,中島 淳
    • Organizer
      第56回日本肺癌学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-11-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 腫瘍特異的遺伝子変異抗原(Neo-antigen)を標的としたがん免疫治療とモニタリング2015

    • Author(s)
      垣見和宏
    • Organizer
      第13回日本臨床腫瘍学会学術集会
    • Place of Presentation
      ロイトン札幌(北海道札幌市)
    • Year and Date
      2015-07-16
    • Related Report
      2015 Research-status Report
  • [Presentation] In silico prediction of neoantigen for lung cancer targeting shared somatic mutations2015

    • Author(s)
      唐崎 隆弘、長山 和弘、宮井 まなみ、松下 博和、喜久川 真悟、的場 亮、ポール・ホートン、小原 收、垣見 和宏、中島 淳
    • Organizer
      第19回日本がん免疫学会総会
    • Place of Presentation
      伊藤国際学術研究センター(東京都文京区)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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