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Adoptive Immunotherapy using the Lymphocytes transduced with Chmeric Antigen Receptor against Salivary Gland Tumor

Research Project

Project/Area Number 15K20181
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Otorhinolaryngology
Research InstitutionChiba University

Principal Investigator

KUNII Naoki  千葉大学, 医学部附属病院, 助教 (00456047)

Research Collaborator OKAMOTO Yoshitaka  千葉大学, 大学院医学研究院, 教授 (40169157)
June Carl H.  University of Pennsylvania, Professor
MAKITA Yuji  千葉大学, 大学院医学研究院, 特任助教 (90706722)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsがん免疫 / キメラ抗原受容体 / 唾液腺がん / 免疫療法 / 標的分子 / メソテリン / がん免疫療法 / 免疫細胞療法 / NKT細胞 / mesothelin / 唾液腺癌 / トランスレーショナル・リサーチ
Outline of Final Research Achievements

Salivary gland cancers (SGCs) are not sensitive to conventional radiotherapy or chemotherapy regimens. Therefore, the development of a new treatment strategy is of critical importance for improving the prognosis. We examined the expression of mesothelin (MSLN) molecules in SGCs and the efficacy of adoptive cell therapy based on MSLN-specific chimeric antigen receptor (CAR) transduced T cells.
The expression of MSLN molecule was studied in SGC samples obtained from 16 patients as well as an SGC cell line (A-253) and four other cell lines. MSLN was detected in the A-253 cells and most of the surgical specimens to various degrees. Following stimulation with MSLN, MSLN-specific CAR-expressing CD8 T cells were dose-dependently activated. Furthermore, the cytotoxicity of CAR T cells against MSLN-expressing cancer cells was demonstrated.
Therefore, the use of adoptive transfer with MSLN-specific CAR-expressing CD8 T cells against SGCs would be an effective therapy.

Report

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

    (13 results)

All 2016 2015

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Blockade of Programmed Death-1/Programmed Death Ligand pathway enhances the antitumor immunity of human invariant Natural Killer T cells.2016

    • Author(s)
      Kamata T, Suzuki A, Mise N, Ihara F, Takami T, Makita Y, Horinaka A, Harada K, Kunii K, Yoshida S, Yoshino I, Nakayama T, and Motohashi S.
    • Journal Title

      Cancer Immunol Immunother.

      Volume: 65 Issue: 12 Pages: 1477-1489

    • DOI

      10.1007/s00262-016-1901-y

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Invariant NKT cells are resistant to circulating CD15(+) myeloid-derived suppressor cells in patients with head and neck cancer.2016

    • Author(s)
      Horinaka A, Sakurai D, Ihara F, Makita Y, Kunii N, Motohashi S, Nakayama T, Okamoto Y.
    • Journal Title

      Cancer Sci.

      Volume: 107 Issue: 3 Pages: 207-16

    • DOI

      10.1111/cas.12866

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Case of Oropharyngeal Squamous Cell Carcinoma who Developed Sigmoid Colon Perforation after Cetuximab Treatment2016

    • Author(s)
      浜崎佐和子, 國井直樹, 蒔田勇治, 有本昇平, 木谷令, 鈴木猛司, 山崎一樹, 米倉修二, 茶薗英明, 櫻井大樹, 花澤豊行, 岡本美孝
    • Journal Title

      Practica Oto-Rhino-Laryngologica

      Volume: 109 Issue: 11 Pages: 803-808

    • DOI

      10.5631/jibirin.109.803

    • NAID

      130005268091

    • ISSN
      0032-6313, 1884-4545
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Three Cases of Neck Swelling after FNAC (fine-needle aspiration cytology)2016

    • Author(s)
      大塚雄一郎, 根本俊光, 國井直樹, 花澤豊行, 岡本美孝
    • Journal Title

      Nippon Jibiinkoka Gakkai Kaiho

      Volume: 119 Issue: 9 Pages: 1225-1230

    • DOI

      10.3950/jibiinkoka.119.1225

    • NAID

      130005420700

    • ISSN
      0030-6622, 1883-0854
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] 中咽頭癌におけるエピゲノム変化とHPV感染の検討2016

    • Author(s)
      中川拓也, 松坂恵介, 高根希世子, 福世真樹, 太田聡, 中谷行雄, 國井直樹, 櫻井大樹, 花澤豊行, 岡本美孝, 金田篤志
    • Organizer
      日本癌学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 制御性T細胞の機能的分類と臨床経過との関連2016

    • Author(s)
      伊原史英, 櫻井大樹, 本橋新一郎, 國井直樹, 岡本美孝
    • Organizer
      日本癌学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 中下咽頭癌CR例に対するiNKT細胞アジュバント療法の有効性に関するランダム化試験2016

    • Author(s)
      國井直樹, 山崎一樹, 茶薗英明, 花澤豊行, 岡本美孝
    • Organizer
      日本口腔咽頭科学会
    • Place of Presentation
      松江テルサ(島根県・松江市)
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 頭頸部扁平上皮癌患者における制御性T細胞の機能的分画と臨床的意義2016

    • Author(s)
      伊原史英, 堀中敦史, 蒔田勇治, 國井直樹, 櫻井大樹, 岡本美孝
    • Organizer
      日本頭頸部癌学会
    • Place of Presentation
      ソニックシティ(埼玉県・さいたま市)
    • Year and Date
      2016-06-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] 唾液腺がん症例に対する α-galactosylceramideパルス樹状細胞の 鼻粘膜下投与を用いた第Ⅰ/Ⅱ相臨床研究2016

    • Author(s)
      國井直樹
    • Organizer
      第34回日本耳鼻咽喉科免疫アレルギー学会
    • Place of Presentation
      鳥羽国際ホテル(三重県・鳥羽市)
    • Year and Date
      2016-02-06
    • Related Report
      2015 Research-status Report
  • [Presentation] Ⅳ期中下咽頭癌治療後CR例に対する NKT細胞免疫療法に関する 第Ⅱ相ランダム化二重盲検試験2016

    • Author(s)
      國井直樹
    • Organizer
      第26回 日本頭頸部外科学会学術講演会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2016-01-28
    • Related Report
      2015 Research-status Report
  • [Presentation] The phase I / II study about iNKT cell-mediated immunotherapy against salivary gland cancer2015

    • Author(s)
      國井直樹
    • Organizer
      第60回日本唾液腺学会学術集会
    • Place of Presentation
      文教学院大学本郷キャンパス(東京都・文京区)
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
  • [Presentation] The Antigen Specific Immunotherapy Based on Chimeric Antigen Receptor Expressing T cells Targeted to Salivary Gland Tumor2015

    • Author(s)
      Naoki KUNII
    • Organizer
      International Conference of Cancer Immunotherapy and Macrophages 2015
    • Place of Presentation
      東京大学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 Research-status Report
    • Int'l Joint Research
  • [Presentation] 頭頸部がんに対する免疫細胞療法 ~iNKT細胞関連トランスレーショナルリサーチと今後の展望~2015

    • Author(s)
      國井直樹
    • Organizer
      第77回耳鼻咽喉科臨床学会学術講演会
    • Place of Presentation
      オークラアクトシティホテル浜松(静岡県・浜松市)
    • Year and Date
      2015-06-25
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2018-03-22  

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