Development of immune-cell therapy for human T cell lymphoma : Cancer vaccine in combination with allogeneic hematopoietic stem cell transplantation.

• Project/Area Number: 19591121
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Ehime University
• Principal Investigator: FUJIWARA Hiroshi Ehime University, 医学部・附属病院, 講師 (20398291)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 腫瘍免疫 / 造血器悪性腫瘍 / T 細胞性悪性リンパ腫 / 成人T細胞白血病(ATL) / 細胞傷害性T リンパ球 / がんワクチン / 造血幹細胞移植術 / T細胞悪性リンパ / 細胞障害性Tリンパ球(CTL) / 癌ワクチン / 造血幹細胞移植 / T細胞悪性リンパ腫 / 成人T細胞白血病リンパ腫(ATLL) / 同種造血幹細胞移植 / 抗造血器悪性腫瘍ワクチン

Research Abstract

治療抵抗性である成人T細胞性白血病(ATL)を含む末梢性T細胞性悪性リンパ腫(PTCL)の治療成績の向上を目指して、抗腫瘍性細胞傷害性T リンパ球(CTL)を利用する細胞免疫療法の開発研究を行った。臨床では同種免疫を利用して抗腫瘍免疫能を強化したHLA 抗原不適合ドナーからの同種造血幹細胞移植の有効性を示した。基礎研究では造血幹細胞移植と併用して抗腫瘍免疫を強化するガンワクチン開発を目指して腫瘍抗原の同定行った。さらに、ATL の原因ウイルスHTLV-1 関連蛋白(Tax とHBZ)特異的CTL の検討を行い、標的特異的CTL の抗腫瘍活性低下機序の幾つかを明らかにした。

Research Products

• [Journal Article] PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients (2009)
  • Author(s): Kozako T, Yoshimitsu M, Fujiwara H, Masamoto I, Horai S, White I, Akimoto M, Suzuki S, Matsushita K, Uozumi K, Tei C, Arima N.
  • Journal Title: Leukemia 23 Pages: 375-382
  • Peer Reviewed
• [Journal Article] Aurora-A kinase : a novel target of cellular immunotherapy for leukemia (2009)
  • Author(s): Ochi T, Fujiwara H, Suemori K, Azuma T, Yakushijin Y, Hato T, Kuzushima K, Yasukawa M.
  • Journal Title: Blood 113 Pages: 66-74
  • Peer Reviewed
• [Journal Article] Identification of a novel epitope derived from OML66 which is recognized by anti-leukaemia cytotoxic T lymphocytes. (2009)
  • Author(s): Suemori K, Fujiwara H, et al.
  • Journal Title: British Journal of Haematology (in press)
  • Peer Reviewed
• [Journal Article] PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients. (2009)
  • Author(s): Kozako T, Fujiwara H, et al.
  • Journal Title: Leukemia 23 Pages: 375-382
  • Peer Reviewed
• [Journal Article] Aurora-A kinase : a novel target of cellular immunotherapy for leukemia. (2009)
  • Author(s): Ochi T, Fujiwara H, et al.
  • Journal Title: Blood 113 Pages: 66-74
  • Peer Reviewed
• [Journal Article] 抗ATL腫瘍免疫抗原としてのHBZの検討 WS1-2-3 (2009)
  • Author(s): 小川泰司, 藤原 弘, 他
  • Journal Title: 第31回日本造血細胞移植学会総会抄録集 113 Pages: 179-179
  • Peer Reviewed
• [Journal Article] Identification of an epitope derived from CML66, a novel tumor-associated antigen expressed broadly in human leukemia, recognized by human leukocyte antigen-A*2402-restricted cytotoxic T lymphocytes. (2008)
  • Author(s): Suemori K, Fujiwara H, Ochi T, Azuma T, Yamanouchi J, Narumi H, Yakushijin Y, Hato T, Hasegawa H, Yasukawa M.
  • Journal Title: Cancer Science 99 Pages: 1414-9
  • NAID: 10024008706
  • Peer Reviewed
• [Journal Article] Allogeneic stem cell transplantation for refractory adult T-cell leukemia using a non-T-cell-depleted HLA-incompatible family donor graft, with reference to the grown-up child donor to parent recipient setting : report of a pilot study (2008)
  • Author(s): Fujiwara H, Ozaki A, Yoshimitsu M, Hamada H, Masamoto I, Matsushita K, Yasukawa M, Tei C.
  • Journal Title: International Journal of Hematology 87 Pages: 319-326
  • NAID: 10021256219
  • Peer Reviewed
• [Journal Article] Identification of an epitope derived from CML66, a novel tumor-associated antigen expressed broadly in human leukemia, recognized by human leukocyte antigen-A*2402-restricted cytotoxic T lymphocytes. (2008)
  • Author(s): Suemori K, Fujiwara H, et al.
  • Journal Title: Cancer Science 99 Pages: 1414-1419
  • NAID: 10024008706
  • Peer Reviewed
• [Journal Article] Case of a patient with Philadelphia-chromosome-positive acute lymphoblastic leukemia relapsed after myeloablative allogeneic hematopoietic stem cell transplantation treated successfully with imatinib and sequential donor lymphocyte infusions. (2008)
  • Author(s): Yoshimitsu M, Fujiwara H, et al.
  • Journal Title: International Journal of Hematology 88 Pages: 331-335
  • NAID: 10023970479
  • Peer Reviewed
• [Journal Article] Allogeneic Stem cell transplantation for refractory adult T-cell leukemia using a non-T-cell-depleted HLA-incompatible family donor graft, with reference to the grown-up child donor to parent recipient setting : report of a pilot study. (2008)
  • Author(s): Fujiwara H, Ozaki A, et al.
  • Journal Title: International Journal of Hematology 87 Pages: 319-326
  • NAID: 10021256219
  • Peer Reviewed
• [Journal Article] Allogeneic stem cell transplantation for refractory adult adult T-cell leukemia using a non T-cell-depleted HLA-incompatible family donor graft,with reference to the grown-up child donor to parent recipient setting report of a pilot study (2008)
  • Author(s): Fujiwara H, et. al.
  • Journal Title: International Journal of Hematology 87 Pages: 319-326
  • Peer Reviewed
• [Journal Article] Identification of an epitope derived from CML66, a novel tumor-associated antigen broadly expressed in huma n leukemia,recognized by HLA-A^*2402-restricted cytotoxic T lymphocytes (2008)
  • Author(s): Suemori K, Fujiwara H, et. al.
  • Journal Title: Cancer Science (in press)
  • Peer Reviewed
• [Journal Article] Identification of a novel epitope derived from CML66 which is recognized by anti-leukaemia cytotoxic T lymphocytes
  • Author(s): Suemori K, Fujiwara H, Ochi T, Azuma T, Yamanouchi J, Narumi H, Yakushijin Y, Hato T, Yasukawa M.
  • Journal Title: British Journal of Haematology (in press)
  • Peer Reviewed
• [Presentation] Aurora A kinase : a novel target of immunotherapy against human leukemia (2009)
  • Author(s): H. Fujiwara, T. Ochi, et al.
  • Organizer: 35th Annual Meeting of the European Group for Blood and Marrow Transplantation, Presidential Symposium
  • Place of Presentation: Goteborg, Sweden
  • Year and Date: 2009-03-31
• [Presentation] Aurora A kinase : a novel target of immunotherapy against human leukemia (2009)
  • Author(s): Hiroshi Fujiwara, Toshiki Ochi, Taichi Azuma, Kiyotaka Kuzushima, Masaki Yasukawa
  • Organizer: 35^<th> Annual Meeting of the European Group for Blood and Marrow Transplantation
  • Place of Presentation: Goeteborg, Sweden
  • Year and Date: 2009-03-30
• [Presentation] 抗ATL腫瘍免疫抗原としてのHBZの検討 (2009)
  • Author(s): 小川泰司、藤原弘、末盛浩一郎、東太地、松岡雅雄、松元正、安川正貴
  • Organizer: 第31回日本造血細胞移植学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-02-05
• [Presentation] 抗ATL腫瘍免疫抗原としてのHBZの検討 (2009)
  • Author(s): 小川泰司, 藤原弘, 他
  • Organizer: 第31回日本造血細胞移植学会総会WS-1-2-3
  • Place of Presentation: 札幌市
  • Year and Date: 2009-02-05
• [Presentation] Aurora-A kinase : A novel target of cellular immunotherapy for human leukemia. (2008)
  • Author(s): T. Ochi, H. Fujiwara, et al.
  • Organizer: 50th Annual Meeting of American Society of Hematology.
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2008-12-07
• [Presentation] Aurora-A Kinaseを標的とした白血病に対する免疫療法の開発 (2008)
  • Author(s): 越智俊元, 藤原弘, 他
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-10-29
• [Presentation] パーフォリン/グランザイムBを介した細胞傷害活性を示す新たなCD8陽性T細胞株の樹立 (2008)
  • Author(s): 末盛浩一郎, 藤原弘, 他
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-10-29
• [Presentation] HBZ特異的細胞傷害性T細胞クローンの樹立と機能解析 (2008)
  • Author(s): 安川正貴、末盛浩一郎、藤原弘、松岡雅雄
  • Organizer: 第56回日本ウイルス学会総会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-28
• [Presentation] HBZ特異的細胞傷害性T細胞クローンの樹立と機能解析 (2008)
  • Author(s): 安川正貴, 藤原弘, 他
  • Organizer: 第56回日本ウイルス学会総会
  • Place of Presentation: 岡山市
  • Year and Date: 2008-10-28
• [Presentation] 細胞傷害活性を持った新しいCD3+CD8+腫瘍性T細胞株(SF-1)の樹立 (2008)
  • Author(s): 藤原弘, 末盛浩一郎, 他
  • Organizer: 第70回日本血液学会絵会
  • Place of Presentation: 京都市
  • Year and Date: 2008-10-10
• [Presentation] Aurora-A Kinaseを標的とした白血病に対する免疫療法の開発 (2008)
  • Author(s): 越智俊元, 藤原弘, 他
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都市
  • Year and Date: 2008-10-10
• [Presentation] 腫瘍関連抗原CML66の臨床的有用性 (2008)
  • Author(s): 末盛浩一郎, 藤原弘, 他
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都市
  • Year and Date: 2008-10-10
• [Presentation] Perforin/Granzyme系を介した細胞傷害活性を持つCD3+CD8+T細胞リンパ腫細胞株の樹立 (2008)
  • Author(s): 藤原弘, 末盛浩一郎, 他
  • Organizer: 第2回基盤的癌免疫療法研究会
  • Place of Presentation: 大宮市
  • Year and Date: 2008-07-02
• [Presentation] Aurora-A Kinaseを標的とした白血病に対する免疫療法の開発 (2008)
  • Author(s): 越智 俊元, 藤原 弘, 他
  • Organizer: 第12回 基盤的癌免疫療法研究会
  • Place of Presentation: 大宮市
  • Year and Date: 2008-07-02
• [Presentation] Aurora-A kinase : A novel target of cellular immunotherapy for human leukemia (2008)
  • Author(s): Toshiki Ochi, Hiroshi Fujiwara, Koichiro Suemori, Taichi Azuma, Kiyotaka Kuzuhima, Masaki Yasukawa
  • Organizer: 50^<th> Annual Meeting of American Society of Hematology
  • Place of Presentation: San Francisco, California, USA.
• [Presentation] 細胞傷害活性を持った新しいCD3+CD8+腫瘍性T 細胞株(SF-1)の樹立 (2008)
  • Author(s): 藤原弘、末盛浩一郎、東太地、新家敏之、安川正貴
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
• [Presentation] 腫瘍関連抗原CML66 の臨床的有用性 (2008)
  • Author(s): 末盛浩一郎、藤原弘、越智俊元、東太地、成見弘、安川正貴
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
• [Presentation] CTL exhaustion in persistent HTLV-I infection and ATLL is restored through PD-1/PD-L1 pathway (2007)
  • Author(s): Kozako T, Fujiwara H, et. al.
  • Organizer: 49^<TH> Annual meeting and exposition American Society of Hematology
  • Place of Presentation: Atlanta,U.S.A.
  • Year and Date: 2007-12-10
• [Presentation] Aurora-A kinase: A novel target for the immunotherapy against human leukemia (2007)
  • Author(s): Ochi T, Fujiwara H, et. al.
  • Organizer: 49^<TH> Annual meeting and exposition American Society of Hematology
  • Place of Presentation: Atlanta,U.S.A.
  • Year and Date: 2007-12-10
• [Presentation] Cytotoxic T-lymphocyte harnessing CML66 can kill human myeloid leukemia cells,in Vitro (2007)
  • Author(s): Suemori K, Fujiwara H, et. al.
  • Organizer: 49^<TH> Annual meeting and exposition American Society of Hematology
  • Place of Presentation: Atlanta,U.S.A.
  • Year and Date: 2007-12-10
• [Presentation] 新規骨髄性自血病関連抗原CML66に対する細胞傷害性Tリンパ球の誘導 (2007)
  • Author(s): 末盛 浩一郎、藤原 弘, 他
  • Organizer: 第69回日本血液学会・第49回日本臨床血液学会合同総会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-10-13
• [Presentation] HTLV-I陽性donor由来のHTLV-I Tax特異的CTLは移植後早期の移植片対ATL効果に必ずしも寄与しない (2007)
  • Author(s): 藤原 弘, 他
  • Organizer: 第69回日本血液学会・第49回日本臨床血液学会合同総会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-10-12
• [Presentation] Aurora-A特異的CTLの誘導と機能解析 (2007)
  • Author(s): 越智 俊元、藤原 弘, 他
  • Organizer: 第69回日本血液学会・第49回日本臨床血液学会合同総会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-10-12
• [Presentation] Induction and functional analysis of CML66-specific cytotoxic T lymphocytes (2007)
  • Author(s): 末盛 浩一郎、藤原 弘, 他
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-10-05
• [Presentation] Identification of epitopes derived from Aurora-A kinase which induce leukemia-specific CTL (2007)
  • Author(s): 越智 俊元、藤原 弘, 他
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-10-03
• [Presentation] CTL exhaustion in persistent HTLV-1 infection and ATLL is restored through PD-1/PD-L1 pathway. (2007)
  • Author(s): Tomohiro Kozako, Makoto Yoshimitsu, Hiroshi Fujiwara, Izumi Masamoto, Sawako Horai, Masaki Akimoto, Yukio Suruga, Hideaki Kawada, Heiichiro Hamada, Noriko Aoki, Sinsuke Suzuki, Kakushi Matsushita, Kimiharu Uozumi, Chuwa Tei, Naomichi Arima
  • Organizer: 49^<th>Annual meeting of American Society of Hematology 2007
  • Place of Presentation: Atlanta, Georgia, USA
• [Presentation] Aurora-A kinase : A novel target for the immunotherapy against human leukemias. (2007)
  • Author(s): Toshiki Ochi, Hiroshi Fujiwara, Koichiro Suemori, Taichi Azuma, Kiyotaka Kuzushima, Masaki Yasukawa
  • Organizer: 49^<th> Annual meeting of American Society of Hematology 2007
  • Place of Presentation: Atlanta, Georgia, USA
• [Presentation] Cytotoxic T-lymphocyte harnessing CML66 can kill human myeloid leukemia cells, in vitro. (2007)
  • Author(s): Koichiro Suemori, Hiroshi Fujiwara, Toshiki Ochi, Masaki Yasukawa
  • Organizer: 49^<th> Annual meeting of American Society of Hematology 2007
  • Place of Presentation: Atlanta, Georgia, USA
• [Presentation] パーフォリン/グランザイムB を介した細胞傷害活性を示す新たなCD8 陽性T 細胞株の樹立。 (2007)
  • Author(s): 末盛浩一郎、藤原 弘、越智俊元、東太地、安川正貴
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] HTLV-1陽性donor 由来のHTLV-1Tax 特異的CTLは、移植後早期の移植片対ATL効果に必ずしも寄与しない (2007)
  • Author(s): 藤原弘、尾崎厚夫、吉満誠、小迫知弘、濱田平一郎、政元いずみ、安川正貴、鄭忠和
  • Organizer: 第69回日本血液学会総会
  • Place of Presentation: 横浜
• [Presentation] 成人T細胞白血病リンパ腫におけるPD-1/PD-L1経路の関与の検討 (2007)
  • Author(s): 吉満誠、小迫知弘、藤原弘、政元いずみ、鈴木伸介、松下格司、魚住公治、鄭忠和、有馬直道
  • Organizer: 第69回日本血液学会総会
  • Place of Presentation: 横浜
• [Book] Oncogene Proteins : Structure, Functions and Analyses.(Edited by Peter B Murphy and Jason R.)Oncogene proteins : Targets for cancer immuno-cell therapy (2008)
  • Author(s): Fujiwara H, Yasukawa M
  • Publisher: Nova Publishers
• [Book] Oncogene Proteins : Structure, Functions and Analyses. . Edited by Peter B Murphy and Jason R. Clarke、Chapter 2, Oncogene proteins : Targets for cancer immuno-cell therapy. (2008)
  • Author(s): Fujiwara H, Yasukawa M
  • Publisher: Nova Publishers
• [Remarks]
  • URL: http://www.m.ehime-u.ac.jp/school/int.med1/
• [Remarks] 愛媛大学大学院生体統御内科学分野ホームページ
  • URL: http://www.m.ehime-u.ac.jp/school/int.medl/
• [Remarks]
  • URL: http://www.m.ehime-u.ac.jp/school/int.med1/
• [Patent(Industrial Property Rights)] CML66抗原によるがんワクチンの製造 (2007)
  • Inventor(s): 安川正貴、藤原弘、末盛浩一郎
  • Industrial Property Rights Holder: 愛媛大学
  • Industrial Property Number: 2007-179843
  • Filing Date: 2007-07-09
• [Patent(Industrial Property Rights)] HLA-A2拘束性抗原ペプチドおよびその用途(Aurora-Aペプチド) (2007)
  • Inventor(s): 安川正貴、藤原弘、越智俊元
  • Industrial Property Rights Holder: 愛媛大学
  • Industrial Property Number: 2007-139441
  • Filing Date: 2007-05-25