Basic construction of WT1-targetting CAR-T therapy for acute myeloid leukemia

2019 Fiscal Year Annual Research Report

• Project/Area Number: 17K09923
• Research Institution: Mie University
• Principal Investigator: 片山 直之 三重大学, 医学系研究科, 教授 (20185812)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 血液内科学 / 造血器腫瘍 / 急性骨髄性白血病 / 白血病幹細胞 / CD25 / 造血幹細胞 / B1細胞

Outline of Annual Research Achievements

CD25陽性急性骨髄性白血病（AML）の白血病幹細胞（LSC）におけるCD25+CD34+CD38-分画とCD25-CD34+CD38-分画の免疫不全マウスへの一次移植では、ともにヒトAML細胞が生着した。それらの一次マウスからのCD25+CD34+CD38-分画とCD25-CD34+CD38-分画を二次マウスに移植すると、再びともにヒトAML細胞の生着が確認された。LSC分画であるCD25+CD34+細胞とCD25-CD34+細胞をサイトカインの存在下で48時間培養した。CD25+CD34+細胞の培養では、CD25+CD34+細胞とCD25-CD34+細胞が検出される症例とCD25+CD34+細胞だけが検出される症例があった。CD25-CD34+細胞の培養では、CD25+CD34+細胞とCD25-CD34+細胞が検出された。CD25の発現はAMLのLSC分画において変動することが示された。
発作性夜間血色素尿症（PNH）クローン由来のCD19+CD20+CD27+CD43+CD38lo/int B1細胞を６症例の末梢血液で解析した。B1細胞分画内に3.79-8.39%のPNHクローン由来のB1細胞が存在し、その頻度はPNHクローン由来の細胞と正常造血幹細胞由来の細胞では差が認められず、PNHの病態がB1細胞の分化に影響を与えていないと考えられる。24～35ヶ月の間隔で採取された検体の解析から、一定期間はPNHクローン由来造血幹細胞がB1細胞の産生をしている可能性が高い。２種類のPIGA遺伝子に変異をもつ症例と１種類のPIGA遺伝子に変異をもつ２症例において、PIGA遺伝子変異をB1細胞分画に検出することができた。PNHだけでなく、もう１つの造血幹細胞に遺伝子異常を認めるが、その造血幹細胞が多分化能を保持している慢性骨髄性白血病（CML）においても同様の結果が得られた。

Research Products

• [Journal Article] Guest editorial: B1 cells: their ontogeny and malignant counterpart (2020)
  • Author(s): Katayama N
  • Journal Title: International Journal of Hematology Volume: 111 Pages: 619-621
  • DOI: 10.1007/s12185-020-02868-z
  • Peer Reviewed
• [Journal Article] Ontogeny of human B1 cells (2020)
  • Author(s): Kageyama Y, Katayama N
  • Journal Title: International Journal of Hematology Volume: 111 Pages: 628-633
  • DOI: 10.1007/s12185-019-02775-y
  • Peer Reviewed
• [Journal Article] Genetic polymorphisms and vincristine-induced peripheral neuropathy in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy (2020)
  • Author(s): Sawaki A, Miyazaki K, Yamaguchi M, Takeuchi T, Kobayashi K, Imai H, Tawara I, Ono R, Nosaka T, Katayama N
  • Journal Title: International Journal of Hematology Volume: 111 Pages: -
  • DOI: 10.1007/s12185-020-02832-x
  • Peer Reviewed
• [Journal Article] First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors (2020)
  • Author(s): Ishihara M, Tono Y, Miyahara Y, Muraoka D, Harada N, Kageyama S, Sasaki T, Hori Y, Soga N, Uchida K, Shiraishi T, Sato E, Kanda H, Mizuno T, Webster GA, Ikeda H, Katayama N, Sugimura Y, Shiku H
  • Journal Title: Cancer Immunology & Immunotherapy Volume: 69 Pages: 663-675
  • DOI: 10.1007/s00262-020-02483-1
  • Peer Reviewed / Open Access
• [Journal Article] Achievement of long-term remission of disseminated histoplasmosis in an AIDS patient (2020)
  • Author(s): Nakamura A, Tawara I, Ino K, Matsumoto T, Hayashi A, Imai H, Muraosa Y, Kamei K, Katayama N
  • Journal Title: Medical Mycology Case Reports Volume: 27 Pages: 25-28
  • DOI: 10.1016/j.mmcr.2019.12.012
  • Peer Reviewed / Open Access
• [Journal Article] Tyrosine kinase inhibitor imatinib augments tumor immunity by depleting effector regulatory T cells (2020)
  • Author(s): Tanaka A, Katayama N, et al (他21名, 21番目)
  • Journal Title: Journal of Experimental Medicine Volume: 217 Pages: -
  • DOI: 10.1084/jem.20191009
  • Peer Reviewed / Open Access
• [Journal Article] DA-EPOCH-R combined with high-dose methotrexate in patients with newly diagnosed stage II-IV CD5-positive diffuse large B-cell lymphoma: a single-arm, open-label, phase 2 study (2020)
  • Author(s): Miyazaki K, Asano N, Yamada T, Miyawaki K, Sakai R, Igarashi T, Nishikori M, Ohata K, Sunami K, Yoshida I, Yamamoto G, Takahashi N, Okamoto M, Yano H, Nishimura Y, Tamaru S, Nishikawa M, Izutsu K, Kinoshita T, Suzumiya J, Ohshima K, Kato K, Katayama N, Yamaguchi M
  • Journal Title: Haematologica Volume: - Pages: 2019.231076
  • DOI: 10.3324/haematol.2019.231076
  • Peer Reviewed
• [Journal Article] Concomitant febuxostat enhances methotrexate-induced hepatotoxicity by inhibiting breast cancer resistance protein (2019)
  • Author(s): Ikemura K, Hiramatsu S, Shinogi Y, Nakatani Y, Tawara I, Iwamoto T, Katayama N, Okuda M
  • Journal Title: Scientific Reports Volume: 9 Pages: -
  • DOI: 10.1038/s41598-019-56900-2
  • Peer Reviewed / Open Access
• [Journal Article] Clinical utility of molecular diagnosis of blood stream infections in allogeneic hematopoietic stem cell transplantation recipients with hematologic malignancies. (2019)
  • Author(s): Fujieda A, Nakase K, Nakamura A, Ohishi K, Sugimoto Y, Monma F, Masuya M, Katayama N
  • Journal Title: Advances in Microbiology Volume: 9 Pages: 971-982
  • DOI: 10.4236/aim.2019.912062
  • Peer Reviewed
• [Journal Article] Evaluation of medication adherence and pharmacokinetics of dasatinib for earlier molecular response in Japanese patients with newly diagnosed chronic myeloid leukemia: a pilot study (2019)
  • Author(s): Iwamoto T, Monma F, Ohishi K, Umino A, Suzuki K, Oka K, Kawakami K, Sekine T, Okuda M, Katayama N
  • Journal Title: Therapeutic Drug Monitoring Volume: 41 Pages: 575-581
  • DOI: 10.1097/FTD.0000000000000639
  • Peer Reviewed
• [Journal Article] Life-threatening tongue and retropharyngeal hemorrhage in a patient with Hemophilia A with inhibitors (2019)
  • Author(s): Kageyama Y, Matsumoto T, Tawara I, Wada H, Katayama N
  • Journal Title: American Journal of Case Reports Volume: 20 Pages: 1022-1026
  • DOI: 10.12659/AJCR.916151
  • Peer Reviewed / Open Access
• [Journal Article] A population of CD20+CD27+CD43+CD38lo/int B1 cells in PNH are missing GPI-anchored proteins and harbor PIGA mutations (2019)
  • Author(s): Kageyama Y, Miwa H, Tawara I, Ohishi K, Masuya M, Katayama N
  • Journal Title: Blood Volume: 134 Pages: 89-92
  • DOI: 10.1182/blood.2019001343
  • Peer Reviewed
• [Journal Article] Improved prognosis of extranodal NK/T cell lymphoma, nasal type of nasal origin but not extranasal origin (2019)
  • Author(s): Yamaguchi M, Suzuki R, Miyazaki K, Amaki J, Takizawa J, Sekiguchi N, Kinoshita S, Tomita N, Wada H, Kobayashi Y, Niitsu N, Ando T, Maeda T, Saito B, Matsuoka H, Sakai R, Kubota N, Masaki Y, Kameoka Y, Asano N, Oguchi M, Katayama N
  • Journal Title: Annals of Hematology Volume: 98 Pages: 1647-1655
  • DOI: 10.1007/s00277-019-03689-9
  • Peer Reviewed
• [Journal Article] Usefulness of the APTT waveform for the diagnosis of DIC and prediction of the outcome or bleeding risk (2019)
  • Author(s): Suzuki K, Wada H, Matsumoto T, Ikejiri M, Ohishi K, Yamashita Y, Imai H, Iba T, Katayama N
  • Journal Title: Thrombosis Journal Volume: 17 Pages: 12-12
  • DOI: 10.1186/s12959-019-0201-0
  • Peer Reviewed
• [Journal Article] Infiltrating CCR2+ monocytes and their progenies, fibrocytes, contribute to colon fibrosis by inhibiting collagen degradation through the production of TIMP-1 (2019)
  • Author(s): Kuroda N, Masuya M, Tawara I, Tsuboi J, Yoneda M, Nishikawa K, Kageyama Y, Hachiya K, Ohishi K, Miwa H, Yamada R, Hamada Y, Tanaka K, Kato T, Takei Y, Katayama N
  • Journal Title: Scientific Reports Volume: 9 Pages: -
  • DOI: 10.1038/s41598-019-45012-6
  • Peer Reviewed / Open Access
• [Journal Article] Successful management of immune thrombocytopenia presenting with lethal alveolar hemorrhage (2019)
  • Author(s): Nagaharu K, Masuya M, Kawakami K, Katayama N
  • Journal Title: Case Reports in Hematology Volume: 2019 Pages: 1-4
  • DOI: 10.1155/2019/5170282
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological features of TAFRO syndrome complicated by acquired hemophilia A and development of cardiopulmonary arrest that were successfully treated with VA-ECMO and tocilizumab (2019)
  • Author(s): Suzuki K, Matsumoto T, Iwashita Y, Ishikura K, Fujioka M, Wada H, Katayama N, Imai H
  • Journal Title: International Journal of Hematology Volume: 109 Pages: 737-743
  • DOI: 10.1007/s12185-019-02604-2
  • Peer Reviewed
• [Journal Article] Elevated plasma levels of soluble C-type lectin-like receptor 2 (CLEC2) in patients with thrombotic microangiopathy (2019)
  • Author(s): Yamashita Y, Suzuki K, Mastumoto T, Ikejiri M, Ohishi K, Katayama N, Suzuki-Inoue K, Wada H
  • Journal Title: Thrombosis Research Volume: 178 Pages: 54-58
  • DOI: 10.1016/j.thromres.2019.03.018
  • Peer Reviewed
• [Presentation] Gene polymorphisms and vincristine-induced neuropathy in patients who received R-CHOP chemotherapy (2019)
  • Author(s): Sawaki A, Miyazaki K, Takeuchi T, Kobayashi K, Imai H, Tawara I, Ono R, Nosaka T, Yamaguchi M, Katayama N
  • Organizer: 第61回アメリカ血液学会
• [Presentation] Novel lymphoid pathway of human plasmacytoid and conventional dendritic cells (2019)
  • Author(s): Nagaharu K, Ohishi K, Katayama N
  • Organizer: 第61回アメリカ血液学会
• [Presentation] シクロフォスファミド抵抗性腫瘍細胞株を用いたマウスMHC半合致移植モデルの作製 (2019)
  • Author(s): 俵 功、西村廣明、坪井順哉、伊野和子、景山裕紀、大石晃嗣、桝屋正浩、片山直之
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] 十二指腸濾胞性リンパ腫における遺伝子変異と浸潤部位 (2019)
  • Author(s): 宮﨑香奈、竹内俊文、山口素子、浅野直子、澤木昭彦、今井 裕、小埜良一、野阪哲哉、小林一彦、田中匡介、片山直之
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] 原発性骨髄線維症に伴う糸球体腎炎と蛋白尿に対してルキソリチニブが有効であった1例 (2019)
  • Author(s): 西村美砂、永春圭規、杉本由香、大石晃嗣、村田智博、桝屋正浩、片山直之
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] 新規薬剤時代におけるIgD型形質細胞白血病に対するタンデム自家／同種移植の経験 (2019)
  • Author(s): 蜂矢健介、藤枝敦史、鈴木和貴、宮下博之、桝屋正浩、片山直之
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] 赤芽球系・巨核球系に異形成を伴ったcryptic PML-RARAと複雑染色体を有する治療関連APL (2019)
  • Author(s): 加島江美子、杉本由香、俵 功、桝屋正浩、片山直之
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] CML患者における第二世代チロシンキナーゼ阻害薬ダサチニブによる血中PSA値の変化 (2019)
  • Author(s): 大石晃嗣、佐々木 豪、高橋直人、片山直之
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] ヒトB1細胞の一部は成人造血幹細胞に由来する (2019)
  • Author(s): 景山裕紀、三輪啓志、俵 功、大石晃嗣、桝屋正浩、片山直之
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] シクロホスファミド抵抗性の腫瘍細胞株を用いたマウスMHC半合致移植モデル (2019)
  • Author(s): 梅澤紘子、俵功、坪井順哉、伊野和子、大石晃嗣、桝屋正浩、宮原慶裕、珠玖洋、片山直之
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] SOD３の発現レベルと腫瘤形成 (2019)
  • Author(s): 神生夏帆、俵 功、坪井順哉、加藤大祐、桝屋正浩、田辺秀之、宮原慶裕、瀬尾尚宏、吉田利通、宮野 悟、珠玖 洋、片山直之
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] NK／T細胞リンパ腫の長期予後と診断治療間隔：NKEA研究の７年追跡調査 (2019)
  • Author(s): 宮﨑香奈、山口素子、鈴木律朗、小口正彦、長谷川正俊、片山直之
  • Organizer: 第78回日本癌学会学術総会
• [Book] 血液専門医テキスト改訂第３版 (2019)
  • Author(s): 片山直之
  • Total Pages: 635
  • Publisher: 日本血液学会
  • ISBN: 978-4-524-24978-7 C3047
• [Book] 血液疾患最新の治療2020-2022 (2019)
  • Author(s): 桝屋正浩、片山直之
  • Total Pages: 390
  • Publisher: 南江堂
  • ISBN: 978-4-524-24978-7