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Mutanome analyses by next generation sequencing and individualized cancer vaccine development in gastric cancer

Research Project

Project/Area Number 25462014
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Wada Ikuo  東京大学, 医学部附属病院, 届出診療医 (80401082)

Co-Investigator(Kenkyū-buntansha) SETO Yasuyuki  東京大学, 医学部附属病院, 教授 (00260498)
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) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords胃がん / 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 / TIL / 個別化がん免疫治療 / 胃癌 / ネオアンチゲン / エクソームシーケンス / ミスセンス変異 / 変異ペプチド / アフィニティ / MHC binding prediction法
Outline of Final Research Achievements

We established the method to identify unique antigens from cancer specific mutations using murine gastric cancer model by combining next generation sequencing with MHC class I binding algorism. We obtained cancer tissues and peripheral blood mononuclear cells (PBMCs) from 29 gastric cancer patients. We analyzed the expression of immune checkpoint molecules and the infiltration of regulatory T cells (Tregs) to understand the immune suppressive tumor microenvironment in 10 patients. We successfully cultured tumor infiltrating lymphocytes (TILs) specifically recognizing autologous tumor cells from 3 patients. We created the system predicting candidate unique antigens and obtained promising samples including cancer tissues and TILs, which are a prerequisite for individualized cancer immunotherapy development in gastric cancer patients.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (30 results)

All 2016 2015 2014 2013 Other

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 2 results,  Open Access: 2 results) Presentation (20 results) (of which Invited: 7 results) Remarks (2 results)

  • [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 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Neoantigen Load, Antigen Presentation Machinery, and Immune Signatures Determine Prognosis in Clear Cell Renal Cell Carcinoma.2016

    • Author(s)
      Matsushita H, Sato Y, Karasaki T, Nakagawa T, Kume H, Ogawa S, Homma Y, Kakimi K.
    • Journal Title

      Cancer Immunol Res.

      Volume: Epub

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2014 Research-status 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 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vaccination With NY-ESO-1 Overlapping Peptides Mixed With Picibanil OK-432 and Montanide ISA-51 in Patients With Cancers Expressing the NY-ESO-1 Antigen2014

    • Author(s)
      Wada H, Isobe M, Kakimi K, Mizote Y, Eikawa S, Sato E, Takigawa N, Kiura K, Tsuji K, Iwatsuki K, Yamasaki M, Miyata H, Matsushita H, Udono H, Seto Y, Yamada K, Nishikawa H, Pan L, Venhaus R, Oka M, Doki Y, Nakayama E.
    • Journal Title

      J Immunother

      Volume: 37(2) Issue: 2 Pages: 84-92

    • DOI

      10.1097/cji.0000000000000017

    • Related Report
      2014 Research-status 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] 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
    • Peer Reviewed
  • [Journal Article] 癌免疫細胞治療(総説)2013

    • Author(s)
      和田 郁雄, 瀬戸 泰之
    • Journal Title

      消化器外科学レビュー2013-'14

      Volume: 2013-'14 Pages: 233-237

    • Related Report
      2013 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(東京都文京区)
    • Year and Date
      2016-02-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [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、川島光明、檜山紀子、村山智紀、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
      2015-11-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] 胃癌患者における腫瘍浸潤リンパ球の免疫チェックポイント分子の発現2015

    • Author(s)
      大平公亮、松下博和、瀬戸泰之、垣見和宏
    • Organizer
      第74回 日本癌学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research 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 Annual Research Report
    • Invited
  • [Presentation] In silico prediction of neoantigen for lung cancer tarageting shared somatic mutations2015

    • Author(s)
      Takahiro Karasaki, Kazuhiro Nagayama, Manami Miyai, Hirokazu Matsushita, Shingo Kikugawa, Ryo Matoba, Paul Horton, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
    • Organizer
      第19回日本がん免疫学会総会(ICCIM2015)
    • Place of Presentation
      伊藤国際学術センター(東京都文京区)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Expression of immune-checkpoint molecules on tumor infiltrating lymphocytes in patients with gastric cancer2015

    • Author(s)
      Kosuke Odaira , Hirokazu Matsushita, Ikuo Wada, Yasuyuki Seto, Nao Fujieda, Yukari Kobayashi, Kazuhiro Kakimi
    • Organizer
      第19回日本がん免疫学会総会(ICCIM2015)
    • Place of Presentation
      伊藤国際学術センター(東京都文京区)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Expression of candidate neoantigens in ccRCC patients and its implication on prognosis2015

    • Author(s)
      Hirokazu Matsushita, Manami Miyai, Yusuke Sato, Tohru Nakagawa, Haruki Kume, Seishi Ogawa, Yukio Homma, Kazuhiro Kakimi
    • Organizer
      第19回日本がん免疫学会総会(ICCIM2015)
    • Place of Presentation
      伊藤国際学術センター(東京都文京区)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Annual Research Report
  • [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 Research-status Report
  • [Presentation] Autologous tumor lysate-loaded dendritic cell vaccination combined with Sunitinib for metastatic renal cell carcinoma2014

    • Author(s)
      Kazuhiro Kakimi, Hirokazu Matsushita, Yutaka Enomoto, Tohru Nakagawa, Haruki Kume and Yukio Honma
    • Organizer
      SITC (Society for immunotherapy of Cancer) 2014
    • Place of Presentation
      Gaylord National Hotel & Convention Center, National Harbor, MD, USA
    • Year and Date
      2014-11-07 – 2014-11-09
    • Related Report
      2014 Research-status Report
  • [Presentation] 食道がんに対するDCF療法と活性化自己γδT細胞治療の併用による治療効果の検討2014

    • Author(s)
      森和彦、松下博和、平野康介、山田和彦、山下裕玄、野村幸代、瀬戸泰之、垣見和宏
    • Organizer
      第52回日本癌治療学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-08-29
    • Related Report
      2014 Research-status 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 Research-status Report
  • [Presentation] TCRディープシーケンスによるNY-ESO-1特異的T細胞のモニタリング2014

    • Author(s)
      垣見和宏、榮川伸吾、磯辺みどり、松下博和、宮井まなみ、細井亮宏、藤枝奈緒、鵜殿平一郎、上中明子、中山睿一
    • 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 Research-status Report
  • [Presentation] 腫瘍内の免疫抑制性環境の制御による腫瘍特異的CTL移入治療の増強2014

    • Author(s)
      細井亮宏、平野康介、松下博和、瀬戸泰之、前川隆司、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 Research-status 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 Research-status 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 Research-status Report
    • Invited
  • [Presentation] Killing and IFN-γ-dependent G1 cell cycle arrest is the mechanism of regulation of tumor growth by Cytotoxic T Lymphocytes.2013

    • Author(s)
      Kazuhiro Kakimi, Hirokazu Matsushita, Akihiro Hosoi, Ryuji Maekawa, and Osamu Ohara
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 腹水貯留を伴う治療抵抗性胃癌に対するγδT細胞腹腔内投与治療の第1相臨床試験2013

    • Author(s)
      和田 郁雄, 松下 博和, 垣見 和宏, 小野山 温那, 李 基成, 奥村 康弘, 谷島 翔, 神保 敬一, 土田 泰昭, 愛甲 丞, 山形 幸徳, 山下 裕玄, 森 和彦, 清水 伸幸, 野村 幸世, 瀬戸 泰之
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡県福岡市
    • Related Report
      2013 Research-status Report
  • [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
    • Related Report
      2013 Research-status 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

    • 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
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] ヒトがん免疫病態の解明と免疫バイオマーカーの同定

    • Author(s)
      河上裕、徐明利、谷口智憲、野地しのぶ、南雲春菜、岡本正人、桜井敏晴、藤田知信、鳥越俊彦、佐藤昇志、中面哲也、垣見和宏、池田裕明、珠玖洋、奥野清隆、杉浦史哲、中山睿一、硲彰一、岡正朗、伊東恭吾
    • Organizer
      第17回日本がん免疫学会総会
    • Place of Presentation
      山口県宇部市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Remarks] 免疫細胞治療学研究室のHP

    • URL

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

    • Related Report
      2014 Research-status Report
  • [Remarks] 免疫細胞治療学(メディネット)講座

    • URL

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

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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