Establishment of the TCR-T cell therapy for adult T-cell leukemia/lymphoma

• Project/Area Number: 18K16095
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Nagoya City University
• Principal Investigator: Masaki Ayako 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (40648044)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ATLL / TCR-T / TCR遺伝子導入Tリンパ球 / IDO1 / 悪性リンパ腫 / 細胞免疫療法 / 抗腫瘍免疫 / 成人T細胞白血病/リンパ腫 / TCR遺伝子改変T細胞 / リンパ系腫瘍 / TCR-T療法

Outline of Final Research Achievements

For establishment of the TCR-T therapy for adult T-cell lymphoma/leukemia, we investigate the factors suppressing antitumor immune responses, and evaluated the activity of NY-EOS-1 specific TCR-T cells. We demonstrated that the percentage of PD-1-positive Tax-CTL was inversely correlated with their function in ATL patients. We found NY-ESO-1 expression in some of ATL patients, and confirmed activity of the NY-EOS-1 specific TCR-T cells against epitope peptide and NY-ESO-1-positive cell line in vitro. The activity of NY-EOS-1 specific TCR-T tended to decrease in the high-kynurenine and low-tryptophan culture medium.

Academic Significance and Societal Importance of the Research Achievements

ATLに対するTCR-T療法は、ドナー確保が容易で、移植片対宿主病に伴うさまざまな合併症を抑制することができるため、幅広い年齢の患者に対して安全に使用できる治療となることが期待できる。
本研究では患者由来ATL細胞でのNY-ESO-1発現と、NY-ESO-1特異的TCR-Tがepitope peptideおよび細胞株を認識して細胞障害活性を発揮することを見出し、NY-ESO-1特異的TCR-T療法の有望性を示した。また、ATL患者由来の腫瘍特異的CTLにおけるPD-1発現とサイトカイン産生の減弱の関連を見出した。ATLに対する免疫チェックポイント阻害剤の有効性が示唆された。

Research Products

• [Journal Article] Case report: Genomic analysis of a therapy-related chronic myelomonocytic leukemia with KMT2A rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features (2023)
  • Author(s): Suzuki Tomotaka、Yokomori Rui、Sanda Takaomi、Kikuchi Takaki、Marumo Yoshiaki、Kinoshita Shiori、Narita Tomoko、Masaki Ayako、Ito Asahi、Ri Masaki、Kusumoto Shigeru、Komatsu Hirokazu、Inagaki Hiroshi、Iida Shinsuke
  • Journal Title: Frontiers in Oncology Volume: 13 Pages: 1-6
  • DOI: 10.3389/fonc.2023.1116418
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Aberrant tryptophan metabolism leads to unfavorable outcomes in lenalidomide‐treated myeloma patients (2022)
  • Author(s): Asano Arisa、Ri M、Masaki Ayako、Maeda Yasuhiro、Tachita Takuto、Hirade Kentaro、Marumo Yoshiaki、Nakashima Takahiro、Hagiwara Shinya、Kinoshita Shiori、Suzuki Tomotaka、Narita Tomoko、Kusumoto Shigeru、Komatsu Hirokazu、Inagaki Hiroshi、Iida Shinsuke
  • Journal Title: Hematological Oncology Volume: - Issue: 3 Pages: 424-433
  • DOI: 10.1002/hon.3108
  • Peer Reviewed
• [Journal Article] <i>CCR7</i> alterations associated with inferior outcome of adult T‐cell leukemia/lymphoma under mogamulizumab treatment (2022)
  • Author(s): Sakamoto Yuma、Ishida Takashi、Masaki Ayako、Murase Takayuki、Ohtsuka Eiichi、Takeshita Morishige、Muto Reiji、Iwasaki Hiromi、Ito Asahi、Kusumoto Shigeru、Nakano Nobuaki、Tokunaga Masahito、Yonekura Kentaro、Tashiro Yukie、Iida Shinsuke、Utsunomiya Atae、Ueda Ryuzo、Inagaki Hiroshi
  • Journal Title: Hematological Oncology Volume: 40 Issue: 5 Pages: 876-884
  • DOI: 10.1002/hon.3072
  • Peer Reviewed / Open Access
• [Journal Article] 7-Amino-4-methylcoumarin as a fluorescent substitute for Schiff’s reagent: a new method that can be combined with hemalum and eosin staining on the same tissue section (2022)
  • Author(s): Takase Hiroshi、Murase Takayuki、Hachisuka Daisuke、Sakamoto Yuma、Sugiura Mariko、Nakano Satsuki、Fujii Keiichiro、Masaki Ayako、Inagaki Hiroshi
  • Journal Title: Biotechnic &amp; Histochemistry Volume: 98 Issue: 1 Pages: 54-61
  • DOI: 10.1080/10520295.2022.2101144
  • Peer Reviewed
• [Journal Article] Clinical impact of the pathological quantification of myocardial fibrosis and infiltrating T lymphocytes using an endomyocardial biopsy in patients with hypertrophic cardiomyopathy (2022)
  • Author(s): Shintani Yasuhiro、Nakayama Takafumi、Masaki Ayako、Yokoi Masashi、Wakami Kazuaki、Ito Tsuyoshi、Goto Toshihiko、Sugiura Tomonori、Inagaki Hiroshi、Seo Yoshihiro
  • Journal Title: International Journal of Cardiology Volume: 362 Pages: 110-117
  • DOI: 10.1016/j.ijcard.2022.05.068
  • Peer Reviewed
• [Journal Article] Pleomorphic adenoma: detection of PLAG1 rearrangement?positive tumor components using whole-slide fluorescence in situ hybridization (2022)
  • Author(s): Murase Takayuki、Ishibashi Kenichiro、Okumura Yoshihide、Ueda Kaori、Nakano Satsuki、Fujii Keiichiro、Masaki Ayako、Nagao Toru、Inagaki Hiroshi
  • Journal Title: Human Pathology Volume: 120 Pages: 26-34
  • DOI: 10.1016/j.humpath.2021.11.010
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma (2021)
  • Author(s): Sakamoto Yuma、Ishida Takashi、Masaki Ayako、Takeshita Morishige、Iwasaki Hiromi、Yonekura Kentaro、Tashiro Yukie、Ito Asahi、Kusumoto Shigeru、Iida Shinsuke、Utsunomiya Atae、Ueda Ryuzo、Inagaki Hiroshi
  • Journal Title: Cancer Science Volume: 113 Issue: 1 Pages: 349-361
  • DOI: 10.1111/cas.15191
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of TP53 mutations in adult T‐cell leukemia/lymphoma (2021)
  • Author(s): Sakamoto Yuma、Ishida Takashi、Masaki Ayako、Murase Takayuki、Takeshita Morishige、Muto Reiji、Iwasaki Hiromi、Ito Asahi、Kusumoto Shigeru、Nakano Nobuaki、Tokunaga Masahito、Yonekura Kentaro、Tashiro Yukie、Iida Shinsuke、Utsunomiya Atae、Ueda Ryuzo、Inagaki Hiroshi
  • Journal Title: British Journal of Haematology Volume: 195 Issue: 4 Pages: 571-584
  • DOI: 10.1111/bjh.17749
  • Peer Reviewed / Open Access
• [Journal Article] Expression of cancer testis antigens in thymic epithelial tumors (2021)
  • Author(s): Sakane Tadashi、Murase Takayuki、Okuda Katsuhiro、Masaki Ayako、Nakanishi Ryoichi、Inagaki Hiroshi
  • Journal Title: Pathology International Volume: 71 Issue: 7 Pages: 471-479
  • DOI: 10.1111/pin.13103
  • Peer Reviewed
• [Journal Article] Newly diagnosed follicular lymphoma during pembrolizumab treatment for lung cancer (2021)
  • Author(s): Marumo Yoshiaki、Kusumoto Shigeru、Masaki Ayako、Nakashima Takahiro、Kikuchi Takaki、Mori Fumiko、Komatsu Hirokazu、Inagaki Hiroshi、Iida Shinsuke、Inagaki Atsushi
  • Journal Title: International Journal of Hematology Volume: 114 Issue: 2 Pages: 280-285
  • DOI: 10.1007/s12185-021-03135-5
  • Peer Reviewed
• [Journal Article] Clinical significance of CD28 gene‐related activating alterations in adult T‐cell leukaemia/lymphoma (2020)
  • Author(s): Sakamoto Yuma、Ishida Takashi、Masaki Ayako、Takeshita Morishige、Iwasaki Hiromi、Yonekura Kentaro、Tashiro Yukie、Ito Asahi、Kusumoto Shigeru、Utsunomiya Atae、Iida Shinsuke、Ueda Ryuzo、Inagaki Hiroshi
  • Journal Title: British Journal of Haematology Volume: 192 Issue: 2 Pages: 281-291
  • DOI: 10.1111/bjh.17211
  • Peer Reviewed
• [Journal Article] Immunohistochemistry for CCR4 C‐terminus predicts CCR4 mutations and mogamulizumab efficacy in adult T‐cell leukemia/lymphoma (2020)
  • Author(s): Fujii Keiichiro、Sakamoto Yuma、Masaki Ayako、Murase Takayuki、Tashiro Yukie、Yonekura Kentaro、Utsunomiya Atae、Ito Asahi、Kusumoto Shigeru、Iida Shinsuke、Ueda Ryuzo、Ishida Takashi、Inagaki Hiroshi
  • Journal Title: The Journal of Pathology: Clinical Research Volume: 7 Issue: 1 Pages: 52-60
  • DOI: 10.1002/cjp2.180
  • Peer Reviewed
• [Journal Article] Clinical significance of tryptophan catabolism in follicular lymphoma (2020)
  • Author(s): Masaki Ayako、Ishida Takashi、Maeda Yasuhiro、Ito Asahi、Suzuki Susumu、Narita Tomoko、Kinoshita Shiori、Yoshida Takashi、Ri Masaki、Kusumoto Shigeru、Komatsu Hirokazu、Inagaki Hiroshi、Ueda Ryuzo、Choi Ilseung、Suehiro Youko、Iida Shinsuke
  • Journal Title: Hematological Oncology Volume: 38 Issue: 5 Pages: 742-753
  • DOI: 10.1002/hon.2804
  • Peer Reviewed / Open Access
• [Journal Article] Robust CD8+ T-cell proliferation and diversification after mogamulizumab in patients with adult T-cell leukemia-lymphoma (2020)
  • Author(s): Saito Masato、Ishii Toshihiko、Urakawa Itaru、Matsumoto Asuka、Masaki Ayako、Ito Asahi、Kusumoto Shigeru、Suzuki Susumu、Takahashi Takeshi、Morita Akimichi、Inagaki Hiroshi、Iida Shinsuke、Ishida Takashi
  • Journal Title: Blood Advances Volume: 4 Issue: 10 Pages: 2180-2191
  • DOI: 10.1182/bloodadvances.2020001641
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological significance of EGFR pathway gene mutations and CRTC1/3‐MAML2 fusions in salivary gland mucoepidermoid carcinoma (2020)
  • Author(s): Morita Maki、Murase Takayuki、Okumura Yoshihide、Ueda Kaori、Sakamoto Yuma、Masaki Ayako、Kawakita Daisuke、Tada Yuichiro、Nibu Ken‐Ichi、Shibuya Yasuyuki、Inagaki Hiroshi
  • Journal Title: Histopathology Volume: X Issue: 7 Pages: 1013-1022
  • DOI: 10.1111/his.14100
  • Peer Reviewed
• [Journal Article] A novel pathophysiologic link between upper and lower airways in patients with chronic rhinosinusitis: Association of sputum periostin levels with upper airway inflammation and olfactory function (2020)
  • Author(s): Kanemitsu Y, Suzuki M, Fukumitsu K, Asano T, Takeda N, Nakamura Y, Ozawa Y, Masaki A, Ono J, Kurokawa R, Yap J, Nishiyama H, Fukuda S, Ohkubo H, Maeno K, Ito Y, Oguri T, Izuhara K, Takemura M, Niimi A
  • Journal Title: World Allergy Organ J Volume: 13
  • Peer Reviewed / Open Access
• [Journal Article] Central pathology review of salivary gland adenoid cystic carcinoma (2020)
  • Author(s): Ueda K、Murase T、Nagao T、Kusafuka K、Urano M、Yamamoto H、Nakaguro M、Taguchi K、Masaki A、Hirai H、Kawakita D、Tsukahara K、Hato N、Nagao T、Fujimoto Y、Sakurai K、Hanai N、Kano S、Onitsuka T、Okami K、Nibu K、Tada Y、Kawata R、Inagaki H
  • Journal Title: Head & Neck Volume: X Issue: 8 Pages: 1721-1727
  • DOI: 10.1002/hed.26081
  • Peer Reviewed
• [Journal Article] CCR4 Is Rarely Expressed in CCR4-mutated T/NK-cell Lymphomas Other Than Adult T-cell Leukemia/Lymphoma (2019)
  • Author(s): Yuma Sakamoto, Keiichiro Fujii, Shunji Murase, Satsuki Nakano, Ayako Masaki, Takayuki Murase, Shigeru Kusumoto, Shinsuke Iida, Atae Utsunomiya, Ryuzo Ueda, Takashi Ishida, Hiroshi Inagaki
  • Journal Title: Int J Hematol Volume: 110 Issue: 4 Pages: 389-392
  • DOI: 10.1007/s12185-019-02728-5
  • Peer Reviewed
• [Journal Article] Plasma cell myeloma positive for t(14;20) with relapse in the central nervous system (2019)
  • Author(s): Murase Takayuki、Inagaki Atsushi、Masaki Ayako、Fujii Keiichiro、Narita Tomoko、Ri Masaki、Hanamura Ichiro、Iida Shinsuke、Inagaki Hiroshi
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 59 Issue: 3 Pages: 135-139
  • DOI: 10.3960/jslrt.19011
  • NAID: 130007720089
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed / Open Access
• [Journal Article] Immunohistochemistry for identification ofCCND1,NSD2, andMAFgene rearrangements in plasma cell myeloma (2019)
  • Author(s): Murase Takayuki、Ri Masaki、Narita Tomoko、Fujii Keiichiro、Masaki Ayako、Iida Shinsuke、Inagaki Hiroshi
  • Journal Title: Cancer Science Volume: - Issue: 8 Pages: 2600-2606
  • DOI: 10.1111/cas.14109
  • Peer Reviewed / Open Access
• [Journal Article] A mutation analysis of the EGFR pathway genes, RAS , EGFR , PIK3CA , AKT1 and BRAF , and TP53 gene in thymic carcinoma and thymoma type A/B3 (2019)
  • Author(s): Sakane Tadashi、Murase Takayuki、Okuda Katsuhiro、Saida Kosuke、Masaki Ayako、Yamada Takeshi、Saito Yushi、Nakanishi Ryoichi、Inagaki Hiroshi
  • Journal Title: Histopathology Volume: 75 Issue: 5 Pages: 755-766
  • DOI: 10.1111/his.13936
  • Peer Reviewed
• [Journal Article] Impact of chromosomal abnormalities on the efficacy of lenalidomide plus dexamethasone treatment in patients with relapsed/refractory multiple myeloma. (2019)
  • Author(s): Yoshida T, Ri M, Fujinami H, Oshima Y, Tachita T, Marumo Y, Sasaki H, Kinoshita S, Totani H, Narita T, Masaki A, Ito A, Kusumoto S, Ishida T, Komatsu H, Iida S
  • Journal Title: Int J Hematol Volume: 110 Issue: 2 Pages: 228-236
  • DOI: 10.1007/s12185-019-02669-z
  • Peer Reviewed
• [Journal Article] Expression analysis of two SLAM family receptors, SLAMF2 and SLAMF7, in patients with multiple myeloma (2019)
  • Author(s): Ashour R, Ri M, Aly SS, Yoshida T, Tachita T, Kanamori T, Aoki S, Kinoshita S, Narita T, Totani H, Masaki A, Ito A, Kusumoto S, Komatsu H, Mansour S, Elsaied AA, Iida S
  • Journal Title: Int J Hematol Volume: 110 Issue: 1 Pages: 69-76
  • DOI: 10.1007/s12185-019-02649-3
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mogamulizumab treatment elicits autoantibodies attacking the skin in patients with adult T cell leukemia-lymphoma (2019)
  • Author(s): Suzuki Yui、Saito Masato、Ishii Toshihiko、Urakawa Itaru、Matsumoto Asuka、Masaki Ayako、Ito Asahi、Kusumoto Shigeru、Suzuki Susumu、Hiura Masanori、Takahashi Takeshi、Morita Akimichi、Inagaki Hiroshi、Iida Shinsuke、Ishida Takashi
  • Journal Title: Clinical Cancer Research Volume: 印刷中 Issue: 14 Pages: 4388-4399
  • DOI: 10.1158/1078-0432.ccr-18-2575
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human T-cell lymphotropic/leukemia virus type 1 (HTLV-1) Tax-specific T-cell exhaustion in HTLV-1-infected individuals. (2018)
  • Author(s): Masaki A, Ishida T, Suzuki S, Ito A, Narita T, Kinoshita S, Ri M, Kusumoto S, Komatsu H, Inagaki H, Ueda R, Iida S.
  • Journal Title: Cancer Sci Volume: 109 Issue: 8 Pages: 2383-2390
  • DOI: 10.1111/cas.13654
  • Peer Reviewed / Open Access
• [Journal Article] CCR4 mutations associated with superior outcome of adult T-cell leukemia/lymphoma under mogamulizumab treatment (2018)
  • Author(s): Sakamoto Yuma、Ishida Takashi、Masaki Ayako、Murase Takayuki、Yonekura Kentaro、Tashiro Yukie、Tokunaga Masahito、Utsunomiya Atae、Ito Asahi、Kusumoto Shigeru、Iida Shinsuke、Ueda Ryuzo、Inagaki Hiroshi
  • Journal Title: Blood Volume: 132 Issue: 7 Pages: 758-761
  • DOI: 10.1182/blood-2018-02-835991
  • Peer Reviewed / Open Access
• [Journal Article] Cyclin-dependent kinase 9 as a potential specific molecular target in NK-cell leukemia/lymphoma (2018)
  • Author(s): Kinoshita Shiori、Ishida Takashi、Ito Asahi、Narita Tomoko、Masaki Ayako、Suzuki Susumu、Yoshida Takashi、Ri Masaki、Kusumoto Shigeru、Komatsu Hirokazu、Shimizu Norio、Inagaki Hiroshi、Kuroda Taruho、Scholz Arne、Ueda Ryuzo、Sanda Takaomi、Iida Shinsuke
  • Journal Title: Haematologica Volume: 103 Issue: 12 Pages: 2059-2068
  • DOI: 10.3324/haematol.2018.191395
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Clinical significance of tryptophan catabolism in patients with myeloma receiving lenalidomide (2022)
  • Author(s): Arisa Asano, Ayako Masaki, Masaki Ri, Yasuhiro Maeda, Kentaro Hirade, Takuto Tachita, Takahiro Nakashima, Shinya Hagiwara, Tomotaka Suzuki, Tomoko Narita, Asahi Ito, Atsushi inagaki, Shigeru Kusumoto, Hirokazu Komatsu, and Shinsuke Iida
  • Organizer: 第84回日本血液学会学術集会
• [Presentation] Immunosuppressive effect of serum extracellular vesicles from patients with multiple myeloma (2022)
  • Author(s): Shinya Hagiwara, Masaki Ri, Kentaro Hirade, Takahiro Nakashima, Arisa Asano, Tomotaka Suzuki, Tomoko Narita, Ayako Masaki, Asahi Ito, Atsushi Inagaki, Shigeru Kusumoto, Hirokazu Komatsu, Shinsuke Iida
  • Organizer: 第84回日本血液学会学術集会
• [Presentation] Evaluating an Optimal Treatment for DLBCL Patients Relapsed in Central Nervous System (2022)
  • Author(s): Tomotaka Suzuki, Shigeru Kusumoto, Hiroya Hashimoto, Shinya Hagiwara, Hiroya Yano, Takayuki Kanamori, Takaki Kikuchi, Satoshi Kayukawa, Takashi Yoshida, Shiori Kinoshita, Kazuhiro Sasaki, Keiko Oshima, Ayako Masaki, Tomoko Narita, Asahi Ito, Atsushi Inagaki, Masaki Ri, Hirokazu Komatsu, Hiroshi Inagaki, Shinsuke Iida
  • Organizer: 第84回日本血液学会学術集会
• [Presentation] 感染性心内膜炎に類似した臨床像を呈した、本態性血小 板血症から進展した急性骨髄性白血病の一例 (2021)
  • Author(s): 佐藤 真利子、鈴木 智貴、加藤寛之、中山貴文、正木彩子、伊藤 旭、李 政樹、楠本 茂、小松弘和、稲垣 宏、飯田真介
  • Organizer: 日本血液学会 東海地方会
• [Presentation] Clinical significance of TP53 mutations in adult T-cell leukemia/lymphoma (2021)
  • Author(s): 坂本祐真、石田高司、正木彩子、村瀬貴幸、竹下盛重、岩崎浩己、田代幸恵、米倉健太郎、徳永雅仁、伊藤旭、楠本茂、飯田真介、宇都宮與、上田龍三、稲垣宏
  • Organizer: 第61回日本リンパ網内系学会総会
• [Presentation] 第61回日本リンパ網内系学会総会 (2021)
  • Author(s): 丸茂 義晃、吉田 嵩、正木 彩子、松永 尚大、片岡 孝江、稲垣 宏、粥川 哲
  • Organizer: 第61回日本リンパ網内系学会総会
• [Presentation] びまん性大細胞型B細胞リンパ腫におけるindoleamine 2,3-dioxygenase活性の臨床的 (2019)
  • Author(s): 正木彩子、楠本茂、前田康博、上田 佳緒璃、坂本祐真、村瀬貴幸、稲垣宏
  • Organizer: 日本病理学会
• [Presentation] Clinical significance of tryptophan catabolism in newly diagnosed multiple myeloma (2019)
  • Author(s): Ayako Masaki, Arisa Asano, Masaki Ri, Yasuhiro Maeda, Takuto Tachita, Asahi Ito, Shiori Kinoshita, Shigeru Kusumoto, Hirokazu Komatsu, Hiroshi Inagaki, Shinsuke Iida
  • Organizer: 日本血液学会
• [Presentation] Prognostic significance of tryptophan catabolism in newly diagnosed follicular lymphoma (2018)
  • Author(s): Masaki A, Ishida T, Maeda Y, Sakamoto Y, Murase T, Inagaki H
  • Organizer: The 107th Annual Meeting of The Japanease Society of Pathology
• [Presentation] Diffuse large B-cell lymphomaの予後におけるトリプトファン代謝の意義 (2018)
  • Author(s): 正木彩子、楠本茂、前田康博、成田朋子、伊藤旭、木下史緒理、吉田嵩、李政樹、小松弘和、石田高司、稲垣宏、上田龍三、飯田真介
  • Organizer: 第80回日本血液学会学術集会
• [Remarks] 名古屋市立大学大学院医学研究科 臨床病態病理学 業績集
  • URL: http://www.med.nagoya-cu.ac.jp/patho2.dir/mysite1/gyouseki.html
• [Remarks] 名古屋市立大学 臨床病態病理学 業績集
  • URL: http://www.med.nagoya-cu.ac.jp/patho2.dir/mysite1/gyouseki.html
• [Remarks] 名古屋市立大学 血液・腫瘍内科学 教室案内
  • URL: http://ncu-ketsuekishuyo.jp/outline