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Investigation of acquired resistance of PD-1 inhibitor with recycle of CART system

Research Project

Project/Area Number 17K19591
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Tumor biology and related fields
Research InstitutionKyoto University

Principal Investigator

Hamanishi Junzo  京都大学, 医学研究科, 講師 (80378736)

Co-Investigator(Kenkyū-buntansha) 安彦 郁  独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究員 (20508246)
村上 隆介  京都大学, 医学研究科, 特定病院助教 (40782363)
Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords卵巣癌 / がん性腹水 / CART / 腫瘍免疫 / CARTシステム / 癌性腹水 / 腹水濾過濃縮再静注療法(CART) / 免疫逃避 / 癌 / 免疫学
Outline of Final Research Achievements

A large amount of cancer ascitic fluid could be filtrated and be concentrated by CART system in the patients with recurrent ovarian cancer. The optimal extraction of cancer cells and immune cells from the cancer ascites and next, we identified the several genes associated with chemotherapy-resistance. Mouse ovarian cancer cell lines whose expression was suppressed in syngeneic mouse ovarian cancer cell lines for these genes. Cancer ascites model and combined treatment with an inhibitor of these genes significantly reduced cancer ascites and prolonged survival. Similar results were obtained in an immunodeficient PDX model administered with cancer ascites cells collected by CART. The results show the usefulness of monitoring and reuse of the CART method for immune analysis.

Academic Significance and Societal Importance of the Research Achievements

本研究では卵巣癌だけでなく、がん性腹水を生じる他臓器がんにも応用可能であると考えられるため、CART法による、腫瘍局所の多角的な免疫状態のモニタリングや、新たな免疫抑制因子の発現メカニズムの解明、さらには同因子を標的とした新たな治療選択のシーズ開発の基盤として、様々な再利用(リサイクル)が複数のがん種に対して期待でき、限られた医療材料や資源を有効に活用することが示され、今後の腫瘍免疫研究の新たなツールとして期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (46 results)

All 2020 2019 2018 2017

All Journal Article (15 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 12 results,  Open Access: 10 results) Presentation (22 results) (of which Int'l Joint Research: 5 results,  Invited: 12 results) Book (9 results)

  • [Journal Article] Anti-VEGF therapy resistance in ovarian cancer is caused by GM-CSF-induced myeloid-derived suppressor cell recruitment.2020

    • Author(s)
      Horikawa N, Abiko K, Matsumura N, Baba T, Hamanishi J, Yamaguchi K, Murakami R, Taki M, Ukita M, Hosoe Y, Koshiyama M, Konishi I, Mandai M.
    • Journal Title

      Br J Cancer.

      Volume: 122(1) Issue: 6 Pages: 778-788

    • DOI

      10.1038/s41416-019-0725-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acquisition of a side population fraction augments malignant phenotype in ovarian cancer.2019

    • Author(s)
      Yamanoi K, Baba T, Abiko K, Hamanishi J, Yamaguchi K, Murakami R, Taki M, Hosoe Y, Murphy SK, Konishi I, Mandai M, Matsumura N.
    • Journal Title

      Sci Rep.

      Volume: 9(1) Issue: 1 Pages: 14215-14215

    • DOI

      10.1038/s41598-019-50794-w

    • NAID

      120006822513

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analytical performance of a new automated chemiluminescent magnetic immunoassays for soluble PD-1, PD-L1, and CTLA-4 in human plasma.2019

    • Author(s)
      Goto M, Chamoto K, Higuchi K, Yamashita S, Noda K, Iino T, Miura M, Yamasaki T, Ogawa O, Sonobe M, Date H, Hamanishi J, Mandai M, Tanaka Y, Chikuma S, Hatae R, Muto M, Minamiguchi S, Minato N, Honjo T
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 10144-10144

    • DOI

      10.1038/s41598-019-46548-3

    • NAID

      120006724630

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphorylation of STAT1 Serine 727 Enhances Platinum Resistance in Uterine Serous Carcinoma.2019

    • Author(s)
      Zeng X, Baba T, Hamanishi J, Matsumura N, Budiman K, Mise Y, Abiko K, Yamaguchi K, Horikawa N, Huntsman DG, Mulati K, Kitamura S, Taki M, Murakami R, Hosoe Y, Mandai M.
    • Journal Title

      Int J Cancer.

      Volume: 145(6) Issue: 6 Pages: 1635-1647

    • DOI

      10.1002/ijc.32501

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] VISTA expressed in tumour cells regulates T cell function2018

    • Author(s)
      Mulati Kumuluzi、Hamanishi Junzo、Matsumura Noriomi、Chamoto Kenji、Mise Nathan、Abiko Kaoru、Baba Tsukasa、Yamaguchi Ken、Horikawa Naoki、Murakami Ryusuke、Taki Mana、Budiman Kharma、Zeng Xiang、Hosoe Yuko、Azuma Miyuki、Konishi Ikuo、Mandai Masaki
    • Journal Title

      British Journal of Cancer

      Volume: 120 Issue: 1 Pages: 115-127

    • DOI

      10.1038/s41416-018-0313-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genomics to immunotherapy of ovarian clear cell carcinoma: Unique opportunities for management.2018

    • Author(s)
      Oda K, Hamanishi J, Matsuo K, Hasegawa K
    • Journal Title

      Gynecol Oncol

      Volume: 151 Issue: 2 Pages: 381-389

    • DOI

      10.1016/j.ygyno.2018.09.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antitumor Effect of Nivolumab on Subsequent Chemotherapy for Platinum‐Resistant Ovarian Cancer2018

    • Author(s)
      Inayama Yoshihide、Hamanishi Junzo、Matsumura Noriomi、Murakami Ryusuke、Abiko Kaoru、Yamaguchi Ken、Baba Tsukasa、Horie Katsuyuki、Konishi Ikuo、Mandai Masaki
    • Journal Title

      The Oncologist

      Volume: 23 Issue: 11 Pages: 1382-1384

    • DOI

      10.1634/theoncologist.2018-0167

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation.2018

    • Author(s)
      Taki M, Abiko K, Baba T, Hamanishi J, Yamaguchi K, Murakami R, Yamanoi K, Horikawa N, Hosoe Y, Nakamura E, Sugiyama A, Mandai M, Konishi I, Matsumura N.
    • Journal Title

      Nature communications

      Volume: Apr 27;9(1) Issue: 1 Pages: 1685-1685

    • DOI

      10.1038/s41467-018-03966-7

    • NAID

      120006462510

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression.2018

    • Author(s)
      Lin H, Wei S, Hurt EM, Green MD, Zhao L, Vatan L, Szeliga W, Herbst R, Harms PW, Fecher LA, Vats P, Chinnaiyan AM, Lao CD, Lawrence TS, Wicha M, Hamanishi J, Mandai M, Kryczek I, Zou W.
    • Journal Title

      J Clin Invest

      Volume: Apr 2;128(4) Issue: 4 Pages: 1708-1708

    • DOI

      10.1172/jci120803

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 免疫チェックポイント阻害薬―メカニズムと治療効果,有害事象2018

    • Author(s)
      濱西 潤三*, 万代 昌紀
    • Journal Title

      最新医学

      Volume: 73 Pages: 182-194

    • Related Report
      2017 Research-status Report
  • [Journal Article] 婦人科がん 婦人科がんに対するチェックポイント阻害薬の開発動向2018

    • Author(s)
      濱西 潤三*, 万代 昌紀
    • Journal Title

      腫瘍内科

      Volume: 21 Pages: 32-59

    • Related Report
      2017 Research-status Report
  • [Journal Article] 免疫チェックポイントPD-1経路阻害薬の展望2018

    • Author(s)
      濱西 潤三*, 万代 昌紀
    • Journal Title

      Cytometry Research

      Volume: 27 Pages: 39-44

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] がん免疫療法の臨床 がん種別治療 婦人科がんに対するがん免疫療法の新展開 PD-1経路阻害薬への期待2018

    • Author(s)
      濱西 潤三*, 万代 昌紀
    • Journal Title

      医学のあゆみ

      Volume: 263 Pages: 97-103

    • Related Report
      2017 Research-status Report
  • [Journal Article] Cancer immunotherapies targeting the PD-1 signaling pathway2017

    • Author(s)
      Iwai Yoshiko、Hamanishi Junzo、Chamoto Kenji、Honjo Tasuku
    • Journal Title

      J Biomed Sci.

      Volume: 24 Issue: 1 Pages: 26-26

    • DOI

      10.1186/s12929-017-0329-9

    • NAID

      120006309287

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exome Sequencing Landscape Analysis in Ovarian Clear Cell Carcinoma Shed Light on Key Chromosomal Regions and Mutation Gene Networks.2017

    • Author(s)
      Murakami R, Matsumura N, Brown JB, Higasa K, Tsutsumi T, Kamada M, Abou-Taleb H, Hosoe Y, Kitamura S, Yamaguchi K, Abiko K, Hamanishi J, Baba T, Koshiyama M, Okuno Y, Yamada R, Matsuda F, Konishi I, Mandai M.
    • Journal Title

      The American Journal of Pathology

      Volume: 187 Issue: 10 Pages: 2246-2258

    • DOI

      10.1016/j.ajpath.2017.06.012

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Immune checkpoint inhibition for Gynecologic cancers -Perspectives and Issues2019

    • Author(s)
      Junzo Hamanishi.
    • Organizer
      14th World Congress of the International Society for Immunology of Reproduction.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 「臨床研究視点から考える免疫原性の重要性」2019

    • Author(s)
      濵西 潤三
    • Organizer
      第23回 日本がん免疫学会 シンポジウム (日本バイオテラピー学会合同シンポジウム)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 「本邦の婦人科悪性腫瘍に対するトランスレーショナルリサーチ~本邦の婦人科悪性腫瘍に対するアンメットニーズと当科の取り組み~」2019

    • Author(s)
      濵西 潤三
    • Organizer
      第61回日本婦人科腫瘍学会学術講演会 ランチョンセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 「Recent Translational Research of Gynecologic Cancers」2019

    • Author(s)
      Junzo Hamanishi J.
    • Organizer
      第17回日本臨床腫瘍学会学術集会 Gynecologic Cance
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 「婦人科腫瘍学研究室(腫瘍研)の20年」2019

    • Author(s)
      濵西潤三
    • Organizer
      第12 回温知会サマークリニカルフォーラム 教室120周年記念セッション
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 「生殖医学フォーラムの歴史]2019

    • Author(s)
      濵西潤三
    • Organizer
      第24回 生殖医学フォーラム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 「がん免疫療法における免疫制御分子PD-1の基礎と臨床 ーPD-1 / PD-L1の臨床応用ー」2019

    • Author(s)
      濵西 潤三
    • Organizer
      第141回 関西実験動物研究会 招請講演
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 婦人科がんの診断・治療 婦人科がんにおける新たな診断・治療に向けて がん遺伝子パネル検査からがん免疫療法へ2018

    • Author(s)
      濱西 潤三
    • Organizer
      日本婦人科腫瘍学会 学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 婦人科がんの新たな治療薬2018

    • Author(s)
      濱西 潤三
    • Organizer
      日本産科婦人科学会 学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Immune Checkpoint PD-1 Inhibitors for Ovarian Cancers2018

    • Author(s)
      Hamanishi J.
    • Organizer
      The 17th Biennial Meeting of the International Gynecologic Cancer Society (IGCS 2018) 14-16 Sep 2018. Kyoto Symposium.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] New perspectives of PD-1 inhibition for Gynecologic Cancer2018

    • Author(s)
      Hamanishi J.
    • Organizer
      The 17th Biennial Meeting of the International Gynecologic Cancer Society (IGCS 2018) 14-16 Sep 2018. Kyoto Symposium.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Efficacy of Immuno-checkpoint Inhibitors in Ovarian Cancer2018

    • Author(s)
      Hamaninshi J.
    • Organizer
      The International Federation of Gynecology and Obstetrics (FIGO 2018) 14-19, Oct. 2018. Rio de Janeiro, Brazil. Symposium.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] PD-1 signal inhibitors for gynecologic cancers: Future perspectives2017

    • Author(s)
      Hamanishi J
    • Organizer
      The 5th Biennial Meeting of Asian Society of Gynecologic Oncology (ASGO 2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] D-1 signal blockade for ovarian cancer: Perspectives and issues2017

    • Author(s)
      Hamanishi J
    • Organizer
      The 56th Annual Congress of Taiwan Association of Obstetrics and Gynecology The 1st J-K-T Joint Conference of Obstetrics and Gynecology. The 1st J-K-T Joint Conference of Obstetrics and Gynecology.
    • Related Report
      2017 Research-status Report
  • [Presentation] Specific gene signatures and oligoclonal expansion of B cell repertoire with the responders of anti-PD-1 antibody (Nivolumab) for ovarian cancer; Novel predictive biomarkers.2017

    • Author(s)
      Hamanishi J, Murakami R, Mandai M, Matsumura M, Abiko K, Baba T, Hosoe Y, Yamaguchi K, Konishi I.
    • Organizer
      International Symposium on Immune Diversity and Cancer Therapy Kobe 2017. Hyogo, Japan.
    • Related Report
      2017 Research-status Report
  • [Presentation] 免疫チェックポイント阻害薬~今後の展望とピットフォール~2017

    • Author(s)
      濵西潤三
    • Organizer
      第272回 がん研有明病院 学術研究講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] Multi-omics analysis of anti-PD-1 antibody (Nivolumb) treated patients with ovarian cancer2017

    • Author(s)
      濵西潤三
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 免疫チェックポイント阻害薬(抗PD-1抗体、抗PD-L1抗体)の展望と課題2017

    • Author(s)
      濵西潤三
    • Organizer
      第55回日本癌治療学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] PD-1経路阻害薬の現況と展望2017

    • Author(s)
      濵西潤三
    • Organizer
      第15回 日本臨床腫瘍学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 免疫チェックポイント阻害薬(抗PD-1,PD-L1抗体)~卵巣癌における展望と課題2017

    • Author(s)
      濵西潤三
    • Organizer
      第59回 日本婦人科腫瘍学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 免疫チェックポイント療法の展望と課題:卵巣がんに対する戦略2017

    • Author(s)
      濵西潤三
    • Organizer
      第5回 先端治療薬研究会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 免疫チェックポイント阻害薬への期待2017

    • Author(s)
      濵西潤三
    • Organizer
      第14回 日本婦人科がん会議2017
    • Related Report
      2017 Research-status Report
  • [Book] がん免疫療法の個別化を支える新・腫瘍免疫学2019

    • Author(s)
      濵西潤三 (河上 裕 編)
    • Total Pages
      267
    • Publisher
      羊土社
    • ISBN
      9784758103817
    • Related Report
      2019 Annual Research Report
  • [Book] がん免疫の最前線】 免疫チェックポイント阻害薬2019

    • Author(s)
      濱西 潤三, 万代 昌紀
    • Publisher
      BIO Clinica
    • Related Report
      2018 Research-status Report
  • [Book] 本庶佑教授(BIO Clinica編集顧問)ノーベル生理学・医学賞受賞によせて 本庶佑教授のノーベル医学・生理学賞に際して2019

    • Author(s)
      濱西 潤三
    • Publisher
      BIO Clinica
    • Related Report
      2018 Research-status Report
  • [Book] 【婦人科腫瘍の新たな治療戦略】 卵巣がんの新たな治療戦略 免疫チェックポイント阻害薬2018

    • Author(s)
      濱西 潤三, 万代 昌紀
    • Publisher
      Pharma Medica
    • Related Report
      2018 Research-status Report
  • [Book] 免疫チェックポイント阻害薬の治療効果予測のためのバイオマーカー2018

    • Author(s)
      濱西 潤三, 万代 昌紀
    • Publisher
      がん分子標的治療
    • Related Report
      2018 Research-status Report
  • [Book] 実践 臨床生殖免疫学 PD-1/PD-L1経路阻害薬2018

    • Author(s)
      濵西潤三, 万代昌紀
    • Publisher
      中外医学社
    • Related Report
      2018 Research-status Report
  • [Book] 婦人科腫瘍遺伝カウンセリングマニュアル 卵巣がんの治療(外科的治療・内科的治療) 免疫チェックポイント阻害薬2018

    • Author(s)
      濵西潤三, 万代昌紀
    • Publisher
      中外医学社
    • ISBN
      9784498060869
    • Related Report
      2018 Research-status Report
  • [Book] 日本産科婦人科学会 研修ノート 免疫治療の現在と未来 がん免疫療法2018

    • Author(s)
      濵西潤三
    • Publisher
      日本産科婦人科学会
    • Related Report
      2018 Research-status Report
  • [Book] がん免疫療法 : what's now and what's next?2017

    • Author(s)
      影山 愼一、池田 裕明、珠玖 洋、西川 博嘉
    • Total Pages
      286
    • Publisher
      メディカルドゥ
    • ISBN
      9784944157617
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2021-02-19  

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