Anti-viral immuno therapeutic approaches for adult T-cell leukemia

• Project/Area Number: 17013028
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KANNAGI Mari Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 教授 (80202034)
• Co-Investigator(Kenkyū-buntansha): HARASHIMA Nanae 東京医科歯科大学, 大学院・医歯学総合研究科, 助手 (60345311)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥48,500,000 (Direct Cost: ¥48,500,000); Fiscal Year 2009: ¥9,700,000 (Direct Cost: ¥9,700,000); Fiscal Year 2008: ¥9,700,000 (Direct Cost: ¥9,700,000); Fiscal Year 2007: ¥9,700,000 (Direct Cost: ¥9,700,000); Fiscal Year 2006: ¥9,700,000 (Direct Cost: ¥9,700,000); Fiscal Year 2005: ¥9,700,000 (Direct Cost: ¥9,700,000)
• Keywords: ウイルス / 癌 / トラスレーショナルリサーチ / 免疫学 / HTLV-I / ATL / ワクチン / 細胞・組織

Research Abstract

Our previous studies suggested that immunological approaches to activate HTLV-I-specific T-cell response potentially induce prophylactic and therapeutic effects on ATL. In order to verify this notion and apply for bedside, we indicated that vaccination reduced proviral load in a rat model, and that a subpopulation of HTLV-I-carriers showed weak HTLV-I-specific T-cell response and elevated proviral load. Moreover, we discovered an innate immune-mediated mechanism suppressing HTLV-I expression in vivo.

Research Products

• [Journal Article] Stromal cell-mediated suppression of human T-cell leukemia virus type-1 expression in vitro and in vivo through type-I interferon. (2009)
  • Author(s): S. Kinpara, A. Hasegawa, A. Utsunomiya, H. Nishitsuji, H. Furukawa, T. Masuda, M. Kannagi
  • Journal Title: J. Virol. 83 Pages: 5101-5108
• [Journal Article] Impaired Tax-specific T-cell responses with insufficient control of HTLV-1 in a subgroup of individuals at asymptomatic and smoldering stages. (2009)
  • Author(s): Y. Shimizu, A. Takamori, A. Utsunomiya, M. Kurimura, Y. Yamano, M. Hishizawa, A. Hasegawa, F. Kondo, K. Kurihara, N. Harashima, T. Watanabe, J. Okamura, T. Masuda, M. Kannagi
  • Journal Title: Cancer Sci. 100 Pages: 481-489
  • NAID: 10025143429
• [Journal Article] Induction of IL-10- and IFN-g-producing T-cell responses by autoreactive T-cells expressing human T-cell leukemia virus type I Tax. (2009)
  • Author(s): N. Takatsuka, A. Hasegawa, A. Takamori, Y. Shimizu, H. Kato, T. Ohashi, T. Amagasa, T. Masuda, M. Kannagi
  • Journal Title: Int. Immunol 21 Pages: 1089-1100
• [Journal Article] Stromal cell-mediated suppression of human T-cell leukemia virus type-1 expression in vitro and in vivo through type-I interferon (2009)
  • Author(s): S.Kinpara, A.Hasegawa, A.Utsunomiya, H.Nishitsuji, H.Furukawa, T.Masuda, M.Kannagi
  • Journal Title: Journal of Virology 83 Pages: 5101-5108
  • Peer Reviewed
• [Journal Article] Impaired Tax-specific T-cell responses with insufficient control of HTLV-1 in a subgroup of individuals at asymptomatic and smoldering stages (2009)
  • Author(s): Y.Shimizu, A.Takamori, A.Utsunomiya, M.Kurimura, Y.Yamano, M.Hishizawa, A.Hasegawa, F.Kondo, K.Kurihara, N.Harashima, T.Watanabe, J.Okamura, T.Masuda, M.Kannagi
  • Journal Title: Cancer Science 100 Pages: 481-489
  • NAID: 10025143429
  • Peer Reviewed
• [Journal Article] Induction of IL-10-and IFN-g-producing T-cell responses by autoreactive T-cells expressing human T-cell leukemia virus type I Tax (2009)
  • Author(s): N.Takatsuka, A.Hasegawa, A.Takamori, Y.Shimizu, H.Kato, T.Ohashi, T.Amagasa, T.Masuda, M.Kannagi
  • Journal Title: Int.Immunol. 21 Pages: 1089-1100
  • Peer Reviewed
• [Journal Article] Impaired Tax-specific T-cell responses with insufficient control of HTLV-1 in a subgroup of individuals at asymptomatic and smoldering stages (2009)
  • Author(s): Y. Shimizu, A. Takamori, A. Utsunomiya, M. Kurimura, Y.Yamano, M. Hishizawa. A. Hasegawa, F. Kondo, K. Kurihara, N. Harashima, T. Watanabe, J. Okamura, T. Masuda, and M. Kannagi
  • Journal Title: Cancer Science 100 Pages: 481-489
  • NAID: 10025143429
  • Peer Reviewed
• [Journal Article] Stromal cell-mediated suppression of human T-cell leukemia virus type-1 expression in vitro and in vivo through type-I interferon (2009)
  • Author(s): S. Kinpara, A. Hasegawa, A. Utsunomiya, H. Nishitsuji, H. Furukawa, T. Masuda, and M. Kannagi
  • Journal Title: Journal of Virology 83 Pages: 5101-5108
  • Peer Reviewed
• [Journal Article] Allogeneic Hematopoietic stem cell transplantation using reduced-intensity conditioning for adult T cell leukemia/lymphoma: Impact of antithymocyte glogulin on clinical outocome. (2008)
  • Author(s): R. Tanosaki, N. Uike, A. Utsunomiya, Y. Saburi, M. Masuda, M. Tomonaga, T. Eto, M. Hidaka, M. Harada, I. Choi, T. Yamanaka, M. Kannagi, M. Matsuoka, J. Okamura
  • Journal Title: Biology of Blood and Marrow Transplantation 14 Pages: 702-708
• [Journal Article] Allogeneic hematopoietic stem dell transplantation using reduced-intensity conditioning for adult T-cell leukemia/lymphoma : Impact of antithymocyte globulin on clinical outcome (2008)
  • Author(s): R. Tanosaki, N. Uike, A. Utsunomiya, Y. Saburi, M. Masuda, M. Tomonaga, T. Eto, M. Hidaka, M. Harada, I. Choi, T. Yamanaka, M. Kannagi, M. Matsuoka, J. Okamura
  • Journal Title: Biology of Blood and Marrow Transplantation 14 Pages: 702-708
  • Peer Reviewed
• [Journal Article] Allogeneic hematopoietic stem dell transplantation using reduced-intensity conditioning for adult T-cell leukemia/1ymphoma: Impact of antithymocyte globulin on clinical outcome. (2008)
  • Author(s): R. Tanosaki, et. al.
  • Journal Title: Biology of Blood and Marrow Transplantation (印刷中)
  • Peer Reviewed
• [Journal Article] Meeting report on the 13th international conference on human retrovirology: Human T-cell leukemia virus research 30 years after adult T-cell leukemia. (2007)
  • Author(s): M. Matsuoka, T. Watanabe, M. Kannagi, C. Bangham, R. Grasmann, S. Marriott, P. Green., K-T Jeang
  • Journal Title: Cancer Res. 67 Pages: 10638-10641
• [Journal Article] IL-2 withdrawal induces HTLV-1 expression through p38 activation in ATL cell lines. (2007)
  • Author(s): M. Washiyma, K. Nishigaki, N. Ahmed, S. Kinpara, Y. Ishii, N. Kanzawa, T. Masuda, M. Kannagi
  • Journal Title: FEBS Letters 581 Pages: 5207-5212
• [Journal Article] Immunologic control of HTLV-I and Adult T-cell Leukemia. Int. (2007)
  • Author(s): Mari Kannagi
  • Journal Title: J. Hematol 86 Pages: 113-117
• [Journal Article] IL-2 withdrawal induces HTLV-1 expression through p38 activation in ATL cell lines. (2007)
  • Author(s): M. Washiyama, et. all.
  • Journal Title: FEBS Letters 581 Pages: 5207-12
  • Peer Reviewed
• [Journal Article] Immunologic control of HTLV-I and adult T-cell leukemia. (2007)
  • Author(s): M. Kannagi.
  • Journal Title: Int. J. Hematol 86 Pages: 113-117
  • Peer Reviewed
• [Journal Article] Reduction of Human T-cell Leukemia Virus Type I (HTLV-I) Proviral Loads in Orally HTLV-I-infected Rats by Re-immunization with HTLV-I-infected Cells. (2006)
  • Author(s): K. Komori, A. Hasegawa, K. Kurihara, T. Honda, H. Yokozeki, T. Masuda, M. Kannagi
  • Journal Title: J. Virol. 80 Pages: 7375-738
• [Journal Article] Human T-cell leukemia virus type-I (HTLV-I)-specific T-cell responses detected using three-divided glutathione-S-transferase (GST)-Tax fusion proteins. (2006)
  • Author(s): K. Kurihara, Y. Shimizu, A. Takamori, N. Harashima, M. Noji, T. Masuda, A. Utsunomiya, J. Okamura, M. Kannagi
  • Journal Title: Immunol. Methods 313 Pages: 61-73
• [Journal Article] Reduction of Human T-cell Leukemia Virus Type I (HTLV-I) Proviral Loads in Orally HTLV-I-infected Rats by Re-immunization with HTLV-I-infected Cells. (2006)
  • Author(s): K.Komori, A.Hasegawa, K.Kurihara, T.Honda, H.Yokozeki, T.Masuda, M.Kannagi
  • Journal Title: J. Virol 80 Pages: 7375-7738
• [Journal Article] Human T-cell leukemia virus type-I (HTLV-I)-specific T-cell responses detected using three-divided glutathione-S-transferase (GST)-Tax fusion proteins. (2006)
  • Author(s): K.Kurihara, Y.Shimizu, A.Takamori, N.Harashima, M.Noji, T.Masuda, A.Utsunomiya, J.Okamura, M.Kannagi
  • Journal Title: J. Immunol. Methods 313 Pages: 61-73
• [Journal Article] Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-kappa B activation (2006)
  • Author(s): Kanzawa, N., Nishigaki, K., Hayashi, T., Ishii, Y., Furukawa S., Nuro, A., Yasui F., Kohara, M., Morita, K., Matsushima, K., Le, M.Q., Masuda, T., Kannagi, M
  • Journal Title: FEBS Lett 580 Pages: 6807-6812
• [Journal Article] Suppression of human immunodeficiency virus type 1 replication by arginine deiminase of Mycoplasma arginini. (2006)
  • Author(s): Kubo, M., Nishitsuji, H., Kurihara, K., Hayashi, T., Masuda, T., Kannagi.M
  • Journal Title: J Gen Virol 87 Pages: 1589-1593
• [Journal Article] ATLにおける腫瘍免疫研究の進歩と臨床応用の可能性. (2006)
  • Author(s): 神奈木真理
  • Journal Title: 血液・腫瘍科 52 (2) Pages: 134-141
• [Journal Article] 成人T細胞白血病の発症予防と免疫治療の展望 (2006)
  • Author(s): 神奈木真理
  • Journal Title: 日本エイズ学会誌 8 Pages: 82-84
• [Journal Article] Identification of Two New HLA-A*1101-restricted Tax Epitopes Recognized by Cytotoxic T-lymphocytes in an Adult T-cell Leukemia Patient after Hematopoietic Stem Cell Transplantation. (2005)
  • Author(s): N. Harashima, R. Tanosaki, Y. Shimizu, K. Kurihara, T. Masuda, J. Okamura, M. Kannagi
  • Journal Title: J. Virol. J. 79 Pages: 88-1009
• [Journal Article] umor immunity against adult T-cell leukemia. (2005)
  • Author(s): M. Kannagi, N. Harashima, K. Kurihara, T. Ohashi, A. Utsunomiya, R. Tanosaki, M. Masuda, M. Tomonaga, J. Okamura
  • Journal Title: Cancer Sci 96 Pages: 249-255
• [Journal Article] for ATL-RIST study group. Allogeneic stem cell transplantation with reduced conditioning intensity as a novel immunotherapy and antiviral therapy for adult T-cell leukemia/lymphoma. (2005)
  • Author(s): J. Okamura, A. Utsunomiya, R. Tanosaki, N. Uike, S. Sonoda, M. Kannagi, M. Tomonaga, M. Harada, N. Kimura, M. Masuda, F. Kawano, Y. Yufu, H. Hattori, H. Kikuchi, Y. Saburi
  • Journal Title: Blood. 105 Pages: 4143-4145
• [Journal Article] Potential immunogenicity of Adult T cell Leukemia cells in vivo. (2005)
  • Author(s): K. Kurihara, N. Harashima, S. Hanabuchi, M. Masuda, A. Utsunomiya, R. Tanosaki, M. Tomonaga, T. Ohashi, A. Hasegawa, T. Masuda, J. Okamura, Y. Tanaka, M. Kannagi
  • Journal Title: Int. J. Cancer 114 Pages: 257-267
• [Journal Article] Identification of Two New HLA-A*1101-restricted Tax Epitopes Recognized by Cytotoxic T-lymphocytes in an Adult T-cell Leukemia Patient after Hematopoietic Stem Cell Transplantation. (2005)
  • Author(s): N.Harashima, et al.
  • Journal Title: J.Virol. 79 Pages: 10088-10092
• [Journal Article] Tumor immunity against adult T-cell leukemia. (2005)
  • Author(s): M.Kannagi, et al.
  • Journal Title: Cancer Sci. 96 Pages: 249-255
• [Journal Article] Potential immunogenicity of Adult T cell Leukemia cells in vivo. Int. (2005)
  • Author(s): K.Kurihara, et al.
  • Journal Title: Int.J.Cancer 114 Pages: 257-267
• [Presentation] HTLV-Iと免疫:自然免疫と獲得免疫によるHTLV-I発現制御. (2009)
  • Organizer: 第49回リンパ網内系学会シンポジウム
  • Place of Presentation: 淡路
  • Year and Date: 2009-07-10
• [Presentation] HTLV-Iと免疫:自然免疫と獲得免疫によるHTLV-I発現制御 (2009)
  • Author(s): 神奈木真理
  • Organizer: 第49回日本リンパ網内系学会総会シンポジウム
  • Place of Presentation: 淡路
  • Year and Date: 2009-07-10
• [Presentation] Suppression of HTLV-1 expression by stromal cells in vitro and in vivo through type-I interferon responses (2009)
  • Author(s): M.Kannagi, S.Kinpara, A.Hasegawa, A.Utsunomiya, H.Nishitsuji, T.Masuda
  • Organizer: 14^<th> International Conference on Human Retrovirology
  • Place of Presentation: Salvador, Brazil
  • Year and Date: 2009-07-01
• [Presentation] 成人T細胞白血病(ATL)と免疫 (2008)
  • Organizer: H20年度文部科学省科学研究費「がん特定」青少年市民講座
  • Place of Presentation: 鹿児島
  • Year and Date: 2008-10-05
• [Presentation] HTLV-I感染者における免疫応答と疾患発現. (2008)
  • Organizer: 第73回インターフェロンサイトカイン/第19回生体防御/第45回補体シンポジウム/3学会合同集会, ワークショップ
  • Place of Presentation: 札幌
  • Year and Date: 2008-07-11
• [Presentation] HTLV-I感染者における免疫応答と疾患発現 (2008)
  • Author(s): 神奈木真理、長谷川温彦、高塚奈津子
  • Organizer: 第73回インターフェロンサイトカイン/第19回生体防御/第45回補体シンポジウム/3学会合同集会, ワークショップ
  • Place of Presentation: 札幌
  • Year and Date: 2008-07-11
• [Presentation] HTLV-I感染者におけるT細胞応答と疾患. (2008)
  • Organizer: 第29回日本炎症・再生医学会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-07-10
• [Presentation] HTLV-I感染者におけるT細胞応答と疾患 (2008)
  • Author(s): 神奈木真理
  • Organizer: 第29回日本炎症・再生医学会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-07-10
• [Presentation] 成人T細胞白血病(ATL)と免疫. (2008)
  • Organizer: H19年度文部科学省科学研究費「がん特定」青少年市民講座
  • Place of Presentation: 富山
  • Year and Date: 2008-02-03
• [Presentation] 抗ウイルス療法としての同種移植療法:ATL. (2007)
  • Organizer: 第29回日本造血細胞移植学会総会、特別セミナー2
  • Place of Presentation: 福岡
  • Year and Date: 2007-02-17
• [Presentation] Insufficient HTLV-I-specific T-cell response asan ATL risk factor. (2007)
  • Organizer: 日本癌学会シンポジウム
  • Place of Presentation: 横浜
• [Presentation] Immune control of Adult T-cell leukemia. (2007)
  • Organizer: 第6回日中合同癌研究学術会議
  • Place of Presentation: 洞爺湖
• [Presentation] Insufficient HTLV-I-specific T-cell response as an ATL risk factor.(ATL発症の免疫学的危険因子) (2007)
  • Author(s): M. Kannagi, et. al.
  • Organizer: 第66回日本癌学会シンポジウム
  • Place of Presentation: 横浜
• [Presentation] A Crossing of Infection and Tumor Immunityagainst Adult T-cell Leukemia. (2005)
  • Organizer: Japan-UScollaborative meeting for cancerimmunosurveillance and cancer vaccine clinicaltrials
  • Place of Presentation: Sapporo
  • Year and Date: 2005-08-19
• [Book] ウイルス感染と免疫(高田賢蔵、今井章介、小柳義夫編) (2009)
  • Author(s): 神奈木真理
  • Publisher: 南江堂
• [Book] 成人T細胞白血病動物モデルを用いた抗腫瘍ワクチンの開発(山本重夫編) (2009)
  • Author(s): 神奈木真理
  • Publisher: シーエムシー出版
• [Book] 医科ウイルス学、12章ウイルス感染と免疫 (2009)
  • Author(s): 神奈木真理
  • Total Pages: 485
  • Publisher: 南江堂、高田賢蔵編
• [Book] HTLV-1と疾患(渡辺俊樹、上平憲、山口一成編) (2007)
  • Author(s): 神奈木真理
  • Publisher: 分光堂
• [Book] ATLにおける腫瘍免疫.新しい診断と治療のABC 46「潜伏感染ウイルスによる血液疾患」(河敬世編, 最新医学別冊) (2007)
  • Author(s): 神奈木真理
• [Book] HTLV-Iに対するT細胞免疫応答(Virus Report,4(1)) (2007)
  • Author(s): 神奈木真理
• [Book] ATLとHTLV-I感染免疫. 「HTLV-1と疾患」 (2007)
  • Author(s): 神奈木真理
  • Publisher: 分光堂
• [Book] ATLにおける腫瘍免疫研究の進歩と臨床応用の可能性(血液・腫瘍科,52(2)) (2006)
  • Author(s): 神奈木真理
• [Book] 成人T 細胞白血病の発症予防と免疫治療の展望(日本エイズ学会誌,8) (2006)
  • Author(s): 神奈木真理
• [Book] 「HTLV-I 感染症」免疫と疾患(前編)(最新医学 60(3)) (2005)
  • Author(s): 神奈木真理
• [Patent(Industrial Property Rights)] Adult T cell Leukemia Model Animal (2009)
  • Inventor(s): Ohashi Takashi, Kannagi Mari
  • Industrial Property Rights Holder: 科学技術振興事業団
  • Acquisition Date: 2009-10-06
  • Overseas
• [Patent(Industrial Property Rights)] Peptide having HTLV-1-specific CTL-inducing activity (2008)
  • Inventor(s): Harashima N, Kannagi M
  • Industrial Property Rights Holder: Tokyo Medical and Dental University
  • Filing Date: 2008-06-25
• [Patent(Industrial Property Rights)] 成人t細胞白血病モデル動物 (2008)
  • Inventor(s): 大橋貴、神奈木真理
  • Industrial Property Rights Holder: JST
  • Filing Date: 2008-12-05
• [Patent(Industrial Property Rights)] 成人T細胞白血病モデル動物 (2008)
  • Inventor(s): 大橋貴、神奈木真理
  • Industrial Property Rights Holder: 科学技術振興事業団
  • Acquisition Date: 2008-12-05
• [Patent(Industrial Property Rights)] Adult T cell Leukemia Model Animal (2006)
  • Inventor(s): Ohashi Takashi, Kannagi Mari
  • Industrial Property Rights Holder: JST
  • Filing Date: 2006-11-10
• [Patent(Industrial Property Rights)] Adult T cell Leukemi a Model Anima1 (2006)
  • Inventor(s): 大橋 貴、神奈木真理
  • Industrial Property Rights Holder: 科学技術振興事業団
  • Filing Date: 2006-10-11
  • Overseas
• [Patent(Industrial Property Rights)] LA-A11拘束性Tax抗腫瘍エピトープ (2005)
  • Inventor(s): 原嶋奈々江、神奈木真理、田野崎隆二
  • Industrial Property Rights Holder: 東京医科歯科大学
  • Filing Date: 2005-09-22
• [Patent(Industrial Property Rights)] HLA-A11拘束性Tax抗腫瘍エピトープ (2004)
  • Inventor(s): 原嶋奈々江, 神奈木真理, 田野崎隆二
  • Industrial Property Rights Holder: 東京医科歯科大学
  • Filing Date: 2004-09-27