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

• Project/Area Number: 15K20181
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Chiba 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: ¥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.

Research Products

• [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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] A Case of Oropharyngeal Squamous Cell Carcinoma who Developed Sigmoid Colon Perforation after Cetuximab Treatment (2016)
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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
• [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
• [Presentation] The phase I / II study about iNKT cell-mediated immunotherapy against salivary gland cancer (2015)
  • 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
• [Presentation] The Antigen Specific Immunotherapy Based on Chimeric Antigen Receptor Expressing T cells Targeted to Salivary Gland Tumor (2015)
  • 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
  • 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
  • Invited