難治性造血器腫瘍に対する CCR4 抗体を軸とした新規包括的治療法の確立、臨床応用

• 研究課題/領域番号: 22689029
• 研究種目: 若手研究(A)
• 配分区分: 補助金
• 研究分野: 血液内科学
• 研究機関: 名古屋市立大学
• 研究代表者: 石田 高司 名古屋市立大学, 大学院・医学研究科, 准教授 (80405183)
• 研究期間 (年度): 2010 – 2012
• 研究課題ステータス: 完了 (2012年度)
• 配分額: 21,970千円 (直接経費: 16,900千円、間接経費: 5,070千円); 2012年度: 6,500千円 (直接経費: 5,000千円、間接経費: 1,500千円); 2011年度: 6,500千円 (直接経費: 5,000千円、間接経費: 1,500千円); 2010年度: 8,970千円 (直接経費: 6,900千円、間接経費: 2,070千円)
• キーワード: CCR4 / CCR4 抗体 / 制御性 T 細胞 / CTL / ATL / NOG マウス / ポテリジオ / 制御性T細胞 / HTLV-1 / Tax / Mogamulizumab / がん・精巣抗原 / KW-0761 / NOGマウス

研究概要

1. HTLV-1 Tax はATLに対する有望な免疫療法の標的分子である。
2. がん・精巣抗原 はATLに対する有望な免疫療法の標的分子である。
3. 同種造血細胞移植療法は前処置法の種類によらずATLに長期生存をもたらし得る治療法である。
4. モガムリズマブは ATL に対する有効な治療薬である。
5. モガムリズマブによる Treg の除去はがん患者に対し、抗腫瘍免疫を増強する利点がある反面、自己免疫疾患を惹起しうるリスクを有する。

研究成果

• [雑誌論文] Successful salvage therapy using lenalidomide in a patient with relapsed multiple myeloma after allogeneic hematopoietic stem cell transplantation (2013)
  • 著者名/発表者名: Suzuki T, Kusumoto S, Yoshida T, Mori F, Ito A, Ri M, Ishida T, Komatsu H, Niimi A, Iida S
  • 雑誌名: Int J Hematol
  • NAID: 10031168524
• [雑誌論文] Stevens-Johnson Syndrome associated with mogamulizumab treatment of adult T-cell leukemia / lymphoma. (2013)
  • 著者名/発表者名: Ishida T
  • 雑誌名: Cancer Sci. 巻: 104 号: 5 ページ: 647-50
  • DOI: 10.1111/cas.12116
  • 査読あり
• [雑誌論文] Angioimmunoblastic T-cell lymphoma mice model. (2013)
  • 著者名/発表者名: Sato F ,Ishida T, Ito A, Mori F, Masaki A, Takino H, Narita T, Ri M, Kusumoto S, Suzuki S, Komatsu H, Niimi A, Ueda R, Inagaki H, Iida S.
  • 雑誌名: Leuk Res 巻: 37 ページ: 21-7
• [雑誌論文] Bath-PUVA Therapy Decreases Infiltrating CCR4-Expressing Tumor Cells and Regulatory T Cells in Patients With Mycosis Fungoides. (2013)
  • 著者名/発表者名: Kato H
  • 雑誌名: Clin Lymphoma Myeloma Leuk. 巻: Epub ahead 号: 3 ページ: 273-280
  • DOI: 10.1016/j.clml.2012.12.002
  • 査読あり
• [雑誌論文] Angioimmunoblastic T-cell lymphoma mice model. (2013)
  • 著者名/発表者名: Sato F
  • 雑誌名: Leuk Res. 巻: 37 号: 1 ページ: 21-7
  • DOI: 10.1016/j.leukres.2012.09.009
  • 査読あり
• [雑誌論文] Reactivation of hepatitis B virus in a patient with adult T-cell leukemia/lymphoma receiving the anti-CC chemokine receptor 4 antibody mogamulizumab. (2013)
  • 著者名/発表者名: Nakano N
  • 雑誌名: Hepatol Res. 巻: Epub ahead 号: 3 ページ: 354-357
  • DOI: 10.1111/hepr.12117
  • 査読あり
• [雑誌論文] Successful salvage therapy using lenalidomide in a patient with relapsed multiple myeloma after allogeneic hematopoietic stem cell transplantation. (2013)
  • 著者名/発表者名: Suzuki T, Kusumoto S, Yoshida T, Mori F, Ito A, Ri M, Ishida T, Komatsu H, Niimi A, Iida S.
  • 雑誌名: Int J Hematol 巻: in press 号: 4 ページ: 540-543
  • DOI: 10.1007/s12185-013-1301-4
  • NAID: 10031168524
  • 査読あり
• [雑誌論文] Tax is a potential molecular target for immunotherapy of adult T -cell leukemia/lymphoma (2012)
  • 著者名/発表者名: Suzuki S, Masaki A, Ishida T, Ito A, Mori F, Sato F, Narita T, Ri M, Kusumoto S, Komatsu H, Fukumori Y, Nishikawa H, Tanaka Y, Niimi A, Inagaki H, Iida S, Ueda R
  • 雑誌名: Cancer Sci 巻: 103 ページ: 1764-73
• [雑誌論文] Defucosylated Anti-CCR4 Monoclonal Antibody (KW-0761) for Relapsed Adult T-Cell Leukemia-Lymphoma: A Multicenter Phase II Study (2012)
  • 著者名/発表者名: Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S, Saburi Y, Miyamoto T, Takemoto S, Suzushima H, Tsukasaki K, Nosaka K, Fujiwara H, Ishitsuka K, Inagaki H, Ogura M, Akinaga S, Tomonaga M, Tobinai K, Ueda R.
  • 雑誌名: J Clin Oncol 巻: 30 ページ: 837-42
• [雑誌論文] Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma (2012)
  • 著者名/発表者名: *Nishikawa H, *Maeda Y, *Ishida T, Gnjatic S, Sato E, Mori F, Sugiyama D, Ito A, Fukumori Y, Utsunomiya A, Inagaki H, Old LJ, Ueda R, Sakaguchi S.
  • 雑誌名: Blood 巻: 119 ページ: 3097-104
• [雑誌論文] Allogeneic hematopoietic stem cell transplantation for adult T -cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study (2012)
  • 著者名/発表者名: Ishida T, Hishizawa M, Kato K, Tanosaki R, Fukuda T, Taniguchi S, Eto T, Takatsuka Y, Miyazaki Y, Moriuchi Y, Hidaka M, Akashi K, Uike N, Sakamaki H, Morishima Y, Kato K, Suzuki R, Nishiyama T, Utsunomiya A
  • 雑誌名: Blood 巻: 120(8) ページ: 1734-41
• [雑誌論文] Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing. (2012)
  • 著者名/発表者名: Ri M, Tashiro E, Oikawa D, Shinjo S, Tokuda M, Yokouchi Y, Narita T, Masaki A, Ito A, Ding J, Kusumoto S, Ishida T, Komatsu H, Shiotsu Y, Ueda R, Iwawaki T, Imoto M, Iida S
  • 雑誌名: Blood Cancer J 巻: 2(7)
• [雑誌論文] Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model. (2012)
  • 著者名/発表者名: Mori F, Ishida T, Ito A, Sato F, Masaki A, Takino H, Ri M, Kusumoto S, Komatsu H, Ueda R, Inagaki H, Iida S.
  • 雑誌名: Blood Cancer J 巻: 2(4)
• [雑誌論文] Forkhead box P1 overexpression and its clinicopathologic significance in peripheral T-cell lymphoma, not otherwise specified. (2012)
  • 著者名/発表者名: Yamada S, Sato F, Xia H, Takino H, Kominato S, Ri M, Ishida T, Iida S, Inagaki H, Yamada K.
  • 雑誌名: Hum Pathol 巻: 43 ページ: 1322-7
• [雑誌論文] Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study. (2012)
  • 著者名/発表者名: Ishida T
  • 雑誌名: Blood 巻: 120 号: 8 ページ: 1734-41
  • DOI: 10.1182/blood-2012-03-414490
  • 査読あり
• [雑誌論文] Tax is a potential molecular target for immunotherapy of adult T-cell leukemia/lymphoma. (2012)
  • 著者名/発表者名: Suzuki S
  • 雑誌名: Cancer Sci. 巻: 103 号: 10 ページ: 1764-73
  • DOI: 10.1111/j.1349-7006.2012.02371.x
  • 査読あり
• [雑誌論文] Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing. (2012)
  • 著者名/発表者名: Ri M, Tashiro E, Oikawa D, Shinjo S, Tokuda M, Yokouchi Y, Narita T, Masaki A, Ito A, Ding J, Kusumoto S, Ishida T, Komatsu H, Shiotsu Y, Ueda R, Iwawaki T, Imoto M, Iida S.
  • 雑誌名: Blood Cancer J. 巻: 2 号: 7 ページ: e79-e79
  • DOI: 10.1038/bcj.2012.26
  • 査読あり
• [雑誌論文] Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma a multicenter phase II study (2012)
  • 著者名/発表者名: Ishida T.
  • 雑誌名: J Clin Oncol 巻: 30(8) 号: 8 ページ: 837-42
  • DOI: 10.1200/jco.2011.37.3472
  • 査読あり
• [雑誌論文] Cancer/testis antigens are novel targets of immunotherapy for adult T cell leukemia/lymphoma (2012)
  • 著者名/発表者名: Nishikawa H.
  • 雑誌名: Blood 巻: 119(13) 号: 13 ページ: 3097-104
  • DOI: 10.1182/blood-2011-09-379982
  • 査読あり
• [雑誌論文] Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model (2012)
  • 著者名/発表者名: Mori F, Ishida T, Ito A, Sato F, Masaki A, Takino H, Ri M, Kusumoto S, Komatsu H, Ueda R, Inagaki H, Iida S.(corresponding author)
  • 雑誌名: Blood Cancer Journal 巻: (in press)
  • 査読あり
• [雑誌論文] Immunopathogenesis of lymphoma: Focus on CCR4 (2011)
  • 著者名/発表者名: Ishida T, Ueda R
  • 雑誌名: Cancer Sci 巻: 102 ページ: 44-50
  • NAID: 10029288284
• [雑誌論文] Antibody therapy for Adult T-cell leukemia-lymphoma (2011)
  • 著者名/発表者名: Ishida T, Ueda R
  • 雑誌名: Int J Hematol 巻: 94(5) ページ: 443-452
  • NAID: 10030265658
• [雑誌論文] Efficacy of Long-Term Treatment with Low-Dose Thalidomide for Patients with Relapsed/Refractory Multiple Myeloma (2011)
  • 著者名/発表者名: Shimizu K, Murakami H, Sawamura M, Hattori Y, Okamoto S, Miwa A, Sugiura I, Shimazaki C, Taniwaki M, Ishida T, Hayashi T, Kosugi H, Yuge M, Iida S, Ishida T, Sunami K, Asaoku H, Sakai A, Abe M, Takagi T
  • 雑誌名: International Journal of Clinical Medicine 巻: 2 ページ: 570-575
• [雑誌論文] Antibody therapy for Adult T-cell leukemia-lymphoma (2011)
  • 著者名/発表者名: Ishida T, Ueda R.(corresponding author)
  • 雑誌名: Int J Hematol 巻: 94 号: 5 ページ: 443-452
  • DOI: 10.1007/s12185-011-0941-5
  • NAID: 10030265658
  • 査読あり
• [雑誌論文] Immunopathogenesis of lymphoma : Focus on CCR4. 2011 : 102 : 44-50 (2011)
  • 著者名/発表者名: Ishida T, Ueda R.(corresponding author)
  • 雑誌名: Cancer Sci 巻: 102 ページ: 44-50
  • 査読あり
• [雑誌論文] Forkhead box P1 overexpression and its clinicopathological significance in peripheral T-cell lymphoma, not otherwise specified (2011)
  • 著者名/発表者名: Yamada S, Sato F, Xia H, Takino H, Kominato S, Ri M, Ishida T, Iida S, Inagaki H, Yamada K.
  • 雑誌名: Hum Pathol 巻: 2 号: 8 ページ: 570-575
  • DOI: 10.1016/j.humpath.2011.10.013
  • 査読あり
• [雑誌論文] A complement-dependent cytotoxicity-enhancing anti-CD20 antibody mediating potent antitumor activity in the humanized NOD/Shi-scid, IL-2Rγ(null) mouse lymphoma model. (2010)
  • 著者名/発表者名: Sato F, Ito A, Ishida T, Mori F, Takino H, Inagaki A, Ri M, Kusumoto S, Komatsu H, Iida S, Okada N, Inagaki H, Ueda R.
  • 雑誌名: Cancer Immunol Immunother 巻: 59 ページ: 1791-800
• [雑誌論文] Bortezomib-resistant myeloma cell lines: a role for mutated PSMB5 in preventing the accumulation of unfolded proteins and fatal ER stress (2010)
  • 著者名/発表者名: Ri M, Iida S, Nakashima T, Miyazaki H, Mori F, Ito A, Inagaki A, Kusumoto S, Ishida T, Komatsu H, Shiotsu Y, Ueda R
  • 雑誌名: Leukemia 巻: 24 ページ: 1506-12
• [雑誌論文] Reactivation of hepatitis B virus in HBsAg-negative patients with multiple myeloma: two case reports (2010)
  • 著者名/発表者名: Yoshida T, Kusumoto S, Inagaki A, Mori F, Ito A, Ri M, Ishida T, Komatsu H, Iida S, Sugauchi F, Tanaka Y, Mizokami M, Ueda R
  • 雑誌名: Int J Hematol. 巻: 91 ページ: 844-9
  • NAID: 10026511317
• [雑誌論文] Defucosylated humanized anti -CCR4 monoclonal antibody KW-0761 as a novelimmunotherapeutic agent for adult T-cell leukemia/lymphoma (ATLL) (2010)
  • 著者名/発表者名: Ishii T, Ishida T, Utsunomiya A, Inagaki A, Yano H, Komatsu H, Iida S, Imada K, Uchiyama T, Akinaga S, Shitara K, Ueda R.
  • 雑誌名: Clin Cancer Res 巻: 16 ページ: 1520-1531
• [雑誌論文] Phase I Study of KW-0761, a Defucosylated Humanized Anti-CCR4 Antibody, in Relapsed Patients with Adult T-Cell Leukemia-Lymphoma and Peripheral T-Cell Lymphoma (2010)
  • 著者名/発表者名: Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, Yamaguchi K, Yamada Y. Hanada S, Tamura K, Nakamura S, Inagaki H, Ohshima K, Kiyoi H, Ishida T, Matsushima K, Akinaga S, Ogura M, Tomonaga M, Ueda R
  • 雑誌名: J Clin Oncol 巻: 28 ページ: 1591-8
• [雑誌論文] A complement-dependent cytotoxicity-enhancing anti-CD20 antibody mediating potent antitumor activity in the humanized NOD/Shi-scid, IL-2Rγ (null) mouse lymphoma model. (2010)
  • 著者名/発表者名: Sato F, Ito A, Ishida T, Mori F, Takino H, Inagaki A, Ri M, Kusumoto S, Komatsu H, Iida S, Okada N, Inagaki H, Ueda R.
  • 雑誌名: Cancer Immunol Immunother 巻: 59 ページ: 1791-1800
  • 査読あり
• [雑誌論文] Bortezomib-resistant myeloma cell lines : a role for mutated PSMB5 in preventing the accumulation of unfolded proteins and fatal ER stress. (2010)
  • 著者名/発表者名: Ri M, Iida S, Nakashima T, Miyazaki H, Mori F, Ito A, Inagaki A, Kusumoto S, Ishida T, Komatsu H, Shiotsu Y, Ueda R.
  • 雑誌名: Leukemia. 巻: 24 ページ: 1506-1512
  • 査読あり
• [雑誌論文] Reactivation of hepatitis B virus in HBsAg-negative patients with multiple myeloma : two case reports. (2010)
  • 著者名/発表者名: Yoshida T, Kusumoto S, Inagaki A, Mori F, Ito A, Ri M, Ishida T, Komatsu H, Iida S, Sugauchi F, Tanaka Y, Mizokami M, Ueda R.
  • 雑誌名: Int J Hematol. 巻: 91 ページ: 844-849
  • NAID: 10026511317
  • 査読あり
• [雑誌論文] Defucosylated humanized anti-CCR4 monoclonal antibody KW-0761 as a novel immunotherapeutic agent for adult T-cell leukemia/lymphoma (ATLL). (2010)
  • 著者名/発表者名: Ishii T, Ishida T, Utsunomiya A, Inagaki A, Yano H, Komatsu H, Iida S, Imada K, Uchiyama T, Akinaga S, Shitara K, Ueda R.
  • 雑誌名: Clin Cancer Res. 巻: 16 ページ: 1520-1531
  • 査読あり
• [雑誌論文] Phase I Study of KW-0761, a Defucosylated Humanized Anti-CCR4 Antibody, in Relapsed Patients with Adult T-Cell Leukemia-Lymphoma and Peripheral T-Cell Lymphoma. (2010)
  • 著者名/発表者名: Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, Yamaguchi K, Yamada Y.Hanada S, Tamura K, Nakamura S, Inagaki H, Ohshima K, Kiyoi H, Ishida T, Matsushima K, Akinaga S, Ogura M, Tomonaga M, Ueda R.
  • 雑誌名: J Clin Oncol. 巻: 28 ページ: 1591-1598
  • 査読あり
• [雑誌論文] Utsunomiya A. Reactivation of hepatitis B virus in a patient with adult T-cell leukemia-lymphoma receiving the anti-CC chemokine receptor 4 antibody mogamulizumab
  • 著者名/発表者名: Nakano N, Kusumoto S, Tanaka Y, IshidaT, Takeuchi S, Takatsuka Y, Akinaga S, Mizokami M, Ueda R
  • 雑誌名: Hepatol Res 巻: (in press)
• [学会発表] Multicenter Phase II Study of Mogamulizumab (KW-0761), a Defucosylated Anti-CCR4 Antibody, in Patients with Relapsed Peripheral and Cutaneous T-Cell Lymphoma(oral presentation) (2012)
  • 著者名/発表者名: Ishida T, Ogura M, MD, Hatake K,et al
  • 学会等名: 54th ASH Annual Meeting and Exposition
  • 発表場所: Atlanta, GA, USA
• [学会発表] Multicenter Phase II Study of Mogamulizumab (KW-0761), a Defucosylated Anti-CCR4 Antibody, in Patients with Relapsed Peripheral and Cutaneous T-Cell Lymphoma (oral presentation) (2012)
  • 著者名/発表者名: Ishida T, Ogura M, MD, Hatake K, et al.
  • 学会等名: 54th ASH Annual Meeting and Exposition (oral presentation)
  • 発表場所: Atlanta, GA
• [学会発表] Development of the CCR4-targeted mAb therapy for Adult T-cell leukemia/lymphoma (ATL), Symposium 10 HTLV-1/ATL (2011)
  • 著者名/発表者名: Takashi Ishida
  • 学会等名: The XXV Symposium of the International Association for Comparative Research on Leukemia and Related Disease
  • 発表場所: 東京大学(東京)(招待講演)
• [学会発表] Promising Results of An Anti-CCR4 Antibody, KW-0761, for Relapsed Adult T-Cell Leukemia-Lymphoma (ATL) (2011)
  • 著者名/発表者名: K.Tobinai, T.Ishida, K.Yamamoto, N.Uike, K.Tsukasaki, A.Utsunomiya, K.Uozumi, M.Tomonaga, R.Ueda
  • 学会等名: 11th International. Conference on. Malignant Lymphoma
  • 発表場所: Palazzo dei Congressi(スイス)
• [学会発表] Promising results of an anti-CCR4 antibody, KW-0761, for relapsed Adult T-Cell Leukemia-Lymphoma (ATL) (2011)
  • 著者名/発表者名: Atae Utsunomiya, Kensei Tobinai, Kazuhito Yamamoto, Takashi Ishida, Naokuni Uike, Kunihiro Tsukasaki, Kimiharu Uozumi, Masao Tomonaga, Ryuzo Ueda
  • 学会等名: 15th International Conference on Human Retroviruses : HTLV and Related Viruses
  • 発表場所: aula Pieter De Somer(ベルギー)
• [学会発表] Multicenter Phase II Study of KW-0761, a Defucosylated Anti-CCR4 Antibody, In Relapsed Patients with Adult T-Cell Leukemia-Lymphoma (ATL)(oral presentation) (2010)
  • 著者名/発表者名: Ishida T, Joh T, Uike N,et al.
  • 学会等名: 52th ASH Annual Meeting And Exposition
  • 発表場所: ORLAND, FL, USA
  • 年月日: 2010-12-06
• [学会発表] Multicenter Phase II Study of KW-0761, a Defucosylated Anti-CCR4 Antibody, In Relapsed Patients with Adult T-Cell Leukemia-Lymphoma (ATL) (2010)
  • 著者名/発表者名: Takashi Ishida, Tatsuro Joh, Naokuni Uike, Kazuhito Yamamoto, Atae Utsunomiya, Shinichiro Yoshida, Yoshio Saburi, Toshihiro Miyamoto, Shigeki Takemoto, Hitoshi Suzushima, Kunihiro Tsukasaki, Kisato Nosaka, Hiroshi Fujiwara, Kenji Ishitsuka, Hiroshi Inagaki, Michinori Ogura, Shiro Akinaga, Masao Tomonaga, Kensei Tobinai, Ryuzo Ueda.
  • 学会等名: 52th Annual Meeting And Exposition
  • 発表場所: ORLAND, FL(米国)
  • 年月日: 2010-12-06