Development of a novel comprehensive therapy targeting aurora kinase-A for adult T cell leukemia

• Project/Area Number: 23591419
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Ehime University
• Principal Investigator: AZUMA Taichi 愛媛大学, 医学部附属病院, 講師 (10396252)
• Co-Investigator(Renkei-kenkyūsha): YASUKAWA Masaki 愛媛大学, 大学院医学系研究科, 教授 (60127917)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 造血器腫瘍 / 細胞免疫療法 / 細胞傷害性T細胞

Research Abstract

In this study, aiming at a development of novel adoptive immunotherapy against adult T-cell leukemia (ATL) which is one of the most treatment-refractory T-lymphoid malignancy, we newly demonstrated the clinical feasibility of adoptive immunotherapy targeting human telomerase reverse transcriptase (hTERT) for the treatment of ATL, and also demonstrated the potential advantage of Aurora kinase-A (AURKA) as a novel therapeutic target for ATL. In addition, we started to extend our therapeutic strategy against ATL from that based on T-cell receptor gene-modified T-cell to newly designed chimeric receptor gene-modified T cell-based one.

Research Products

• [Journal Article] Analysis of chemotherapy-induced neutropenia and optimal timing for prophylactic use of G-CSF in B-cell non-Hodgkin lymphoma patients treated with R-CHOP (2014)
  • Author(s): Shikata H, Yakushijin Y, Yamanouchi J, Azuma T, Yasukawa M
  • Journal Title: Int J Clin Oncol Volume: 19(1) Pages: 178-85
  • Peer Reviewed
• [Journal Article] Development of a novel redirected T-cell-based adoptive immunotherapy targeting human telomerase reverse transcriptase for adult T-cell leukemia (2013)
  • Author(s): Miyazaki Y, Fujiwara H, Asai H, Ochi F, Ochi T, Azuma T, Ishida T, Okamoto S, Mineno J, Kuzushima K, Shiku H, Yasukawa M
  • Journal Title: Blood Volume: 121(24) Pages: 4894-901
  • Peer Reviewed
• [Journal Article] Development of a novel redirected T-cell-based adoptive immunotherapy targeting human telomerase reverse transcriptase for adult T-cell leukemia. (2013)
  • Author(s): Yasukawa M, et al.
  • Journal Title: Blood Volume: 121 Issue: 24 Pages: 4894-4901
  • DOI: 10.1182/blood-2012-11-465971
  • Peer Reviewed
• [Journal Article] Development of a novel redirected T cell-based adoptive immunotherapy targeting human telomerase reverse transcriptase for adult T-cell leukemia. (2013)
  • Author(s): Miyazaki Y et al.
  • Journal Title: Blood Volume: 未
  • Peer Reviewed
• [Journal Article] Analysis of chemotherapy-induced neutropenia and optimal timing for prophylactic use of G-CSF in B-cell non-Hodgkin lymphoma patients treated with R-CHOP. (2013)
  • Author(s): Shikata H et al.
  • Journal Title: Int J Clin Oncol. Volume: 未 Issue: 1 Pages: 178-185
  • DOI: 10.1007/s10147-013-0523-z
  • Peer Reviewed
• [Journal Article] Role of activation-induced cytidine deaminase in the progression of follicular lymphoma (2012)
  • Author(s): Shikata H, Yakushijin Y, Matsushita N, Sakai A, Sugita A, Nakamura N, Yamanouchi J, Azuma T, Hato T,Yasukawa M
  • Journal Title: Cancer Sci Volume: 103(3) Pages: 415-21
  • Peer Reviewed
• [Journal Article] Aurora kinase A-specific T-cell receptor gene transfer redirects T-lymphocytes to display effective anti-leukemia reactivity (2012)
  • Author(s): Kozo Nagai, et al
  • Journal Title: Blood Volume: 119(2) Issue: 2 Pages: 368-76
  • DOI: 10.1182/blood-2011-06-360354
  • Peer Reviewed
• [Journal Article] Requisite considerations for successful adoptive immunotherapy with engineered T-lymphocytes using tumor antigen-specific T-cell receptor gene transfer. (2011)
  • Author(s): Ochi T, et al
  • Journal Title: Expert Opin Biol Ther. Volume: 11(6) Pages: 699-713
  • Peer Reviewed
• [Presentation] Co-Administration of Gene-Modified CD4^+ T Cells Targeting HLA Class I-Restricted WT1 Epitope Diversely Enhances The Antitumor Effect Mediated By Redirected T-Cell Based Adoptive Immunotherapy Against Human Leukemia (2013)
  • Author(s): Fujiwara H, Azuma T, Yasukawa M, et al
  • Organizer: 55^<th> American Society of Hematology, Annual meeting and Exposition
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2013-12-08
• [Presentation] Human telomerase reverse transcriptase‒specific T-cell receptor gene transfer redirects T cells to display an effective antitumor reactivity against adult T-cell leukemia (2013)
  • Author(s): Fujiwara H, Azuma T, Yasukawa M, et al
  • Organizer: 39^<th> Annual Meeting of the European Group for Blood and Marrow Transplantation
  • Place of Presentation: London, UK
  • Year and Date: 2013-04-08
• [Presentation] 成人T細胞白血病に対するhTERT特異的TCR遺伝子を用いた新たな細胞免疫療法の開発. (2012)
  • Author(s): 宮崎 幸大 他
  • Organizer: 第34回日本造血細胞移植学会総会
  • Place of Presentation: 大阪市
• [Presentation] Human telomerase reverse transcriptase-specific T-cell receptor gene transfer redirects T-lymphocytes to exert effective antitumor reactivity against adult T-cell leukemia. (2011)
  • Author(s): Yukihiro Miyazaki, et al
  • Organizer: The 53th Annual meeting of American Society of Hematology
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Development of a novel gene-immunotherapy for adult T-cell leukemia using hTERT-siTCR gene transfer. (2011)
  • Author(s): Yukihiro Miyazaki, et al
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋市
• [Presentation] Co-Administration of Gene-Modified CD4+ T Cells Targeting HLA Class I-Restricted WT1 Epitope Diversely Enhances The Antitumor Effect Mediated By Redirected T-Cell Based Adoptive Immunotherapy Against Human Leukemia.
  • Author(s): Hiroshi Fujiwara, Fumihiro Ochi, Toshiki Ochi, Sachiko Okamoto, Hiroaki Asai,Yukihiro Miyazaki, Taichi Azuma, Junichi Mineno, Miwako Narita, Kiyotaka Kuzushima, Hiroshi Shiku, Masaki Yasukawa
  • Organizer: 55th American Society of Hematology, Annual meeting and Exposition
  • Place of Presentation: New Orleans, LA, USA
• [Presentation] Human telomerase reverse transcriptase-specific T-cell receptor gene transfer redirects T cells to display an effective antitumor reactivity against adult T-cell leukemia.
  • Author(s): Hiroshi Fujiwara, Yukihiro Miyazaki, Fumihiro Ochi, Hiroaki Asai, Taichi Azuma, Takashi Ishida, Sachiko Okamoto, Junichi Mineno, Kiyotaka Kuzushima, Hiroshi Shiku, Masaki Yasukawa.
  • Organizer: 39th Annual Meeting of the European Group for Blood and Marrow Transplantation
  • Place of Presentation: London, UK
• [Presentation] Preclinical evaluation for renal safety of WT1-targeting adoptive immunotherapy.
  • Author(s): Hiroaki Asai et al.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌市
• [Presentation] キメラ型CD16遺伝子改変T細胞は抗腫瘍性ADCC活性におけるNK細胞の問題点を解決できる可能性がある。
  • Author(s): 藤原 弘 他.
  • Organizer: 第36回日本造血細胞移植学会
  • Place of Presentation: 宜野湾市
• [Presentation] HLA class I拘束性腫瘍抗原特異的TCRを遺伝子導入したCD4陽性T細胞の機能解析。
  • Author(s): 宮崎幸大 他.
  • Organizer: 第16回日本がん免疫学会総会
  • Place of Presentation: 札幌
• [Presentation] 成人T細胞白血病に対するhTERT特異的TCR遺伝子を用いた新たな細胞免疫療法の開発。
  • Author(s): 宮崎幸大 他.
  • Organizer: 第4回造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 金沢
• [Presentation] Redirected T-cell based immunotherapy targeting hTERT displays an anti-tumor reactivity against adult T cell leukemia.
  • Author(s): Hirofumi Ochi et al.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] hTERT-specific TCR gene transduced T cells display an effective anti-tumor reactivity against ATL.
  • Author(s): Yukihiro Miyazaki et al.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Book] 「多発性骨髄腫」高齢者総合診療ノート (2014)
  • Author(s): 東太地、安川正貴
  • Publisher: 日本医事新報社
• [Book] 「組織球・樹状細胞の異常と血球貪食症候群」カラーテキスト血液病学(第2版) (2012)
  • Author(s): 東太地、安川正貴
  • Publisher: 中外医学社
• [Remarks]
  • URL: http://www.m.ehime-u.ac.jp/school/int.med1/