Development of molecular diagnosis and molecule-targeted therapy for leukemia

2009 Fiscal Year Final Research Report

• Project/Area Number: 17015028
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: SUGIYAMA Haruo Osaka University, 大学院・医学系研究科, 教授 (70162906)
• Co-Investigator(Kenkyū-buntansha): OKA Yoshihiro 大阪大学, 大学院・医学系研究科, 講師 (20273691) ; OJI Yusuke 大阪大学, 大学院・医学系研究科, 特任教授 (20294100) ; HOSEN Naoki 大阪大学, 大学院・医学系研究科, 准教授 (10456923) ; FUJIKI Fumihiro 大阪大学, 大学院・医学系研究科, 特任助教(常勤) (40456926)
• Project Period (FY): 2005 – 2009
• Keywords: WT1 / 白血病 / 分子診断 / 分子標的療法 / 免疫療法

Research Abstract

Wilms' tumor gene WT1 is overexpressed in leukemia and almost all types of solid tumors. Therefore, WT1 is a pan-tumor marker and pan-tumor-associated antigen. WT1 mRNA quantitative assay, which can detect minimal residual disease of luekamia at high sensitivity, has been developed and covered by national health insurance from 2007. Furthermore, clinical trials of WT1 peptide-based immunotherapy was begun in 2001 and clinical effect has been showing. This immunotherapy has been developing in Europe and USA and drug product is in progress.

Research Products

• [Journal Article] Prognostic Significance of WT1 mRNA and anti-WT1 Antibody Levels in Peripheral Blood in Patients with Myelodysplastic Syndromes. (2010)
  • Author(s): Tamura H, Dan K, Yokose N, Iwakiri R, Ohta M, Sakamaki H, Tohyama K, Kondo A, Hyodo H, Nakamura K, Yamashita T, Elisseeva O. A, Oka Y, Oji Y, Sugiyama H, Ogata K.
  • Journal Title: Leukemia Research (in press)
  • Peer Reviewed
• [Journal Article] High frequencies of less differentiated and more proliferative WT1-specific CD8+ T cells in bone marrow (BM) in tumor-bearing patients: an important role of BM as a secondary lymphoid organ. (2010)
  • Author(s): Murao A, Oka Y, Tsuboi A, Elisseeva OA, Harada Y, Fujiki F, Nakajima H, Nishida S, Hosen N, Shirakata T, Hashimoto N, Myoui A, Ueda T, Takeda Y, Osaki T, Enomoto T, Yoshikawa H, Kimura T, Oji Y, Kawase I, Sugiyama H.
  • Journal Title: Cancer Science (in press)
  • Peer Reviewed
• [Journal Article] Biased usage of BV gene families of T cell receptors of WT1 (Wilms' tumor gene)-specific CD8+ T cells in patients with myeloid malignancies (2010)
  • Author(s): Tanaka-Harada Y, Kawakami M, Oka Y, Tsuboi A, Katagiri T, Elisseeva O, Nishida S, Shirakata T, Hosen N, Fujiki F, Murao A, Nakajima H, Oji Y, Kanda Y, Kawase I, Sugiyama H.
  • Journal Title: Cancer Science 101 Pages: 594-600
  • Peer Reviewed
• [Journal Article] WT1 peptide immunotherapy for cancer in children and young adults. (2009)
  • Author(s): Hashii Y, Sato E, Ohta H, Oka Y, Sugiyama H, Ozono K.
  • Journal Title: Pediat Blood Cancer 26 Pages: 74-83
  • Peer Reviewed
• [Journal Article] A WT1 protein-derived, naturally processed 16-mer peptide, WT1332, is a promiscuous helper peptide for induction of WT1-specific Th1-type CD4+ T cells. (2008)
  • Author(s): Fujiki F, Oka Y, Kawakatsu M, Tsuboi A, Nakajima H, Elisseeva OA, Harada Y, Li Z, Tatsumi N, Kamino E, Shirakata T, Nishida S, Taniguchi Y, Kawase I, Oji Y, Sugiyama H.
  • Journal Title: Microbiol Immunol 52 Pages: 591-600
  • Peer Reviewed
• [Journal Article] Identification of a WT1 protein-derived peptide, WT1187 as an HLA-A*0206-restricted, WT1-specific CTL epitope" is currently at the following stage of production. (2008)
  • Author(s): Li Z, Oka Y, Tsuboi A, Fujiki F, Harada Y, Nakajima H, Masuda T, Fukuda Y, Kawakatsu M, Morimoto S, Katagiri T, Tatsumi N, Hosen N, Shirakata T, Nishida S, Kawakami Y, Udaka K, Kawase I, Oji Y, Sugiyama H.
  • Journal Title: Microbiol Immunol 52 Pages: 551-8
  • Peer Reviewed
• [Journal Article] Identification and characterization of a WT1 (Wilms' tumor gene) protein-derived HLA-DRB1*0405-restricted 16-mer helper peptide that promotes the induction and activation of WT1-specific cytotoxic T lymphocytes. (2007)
  • Author(s): Fujiki F, Oka Y, Tsuboi A, Kawakami M, Nakajima H, Elisseeva OA, Harada Y, Ito K, Li Z, Tatsumi N, Sakaguchi N, Fujioka T, Masuda T, Yasukawa M, Udaka K, Oji Y, Sugiyama H.
  • Journal Title: J Immunother 30 Pages: 282-93
  • Peer Reviewed
• [Journal Article] Clinical and immunologic responses to very low-dose vaccination with WT1 peptide (5 mug/body) in a patient with chronic myelomonocytic leukemia. (2007)
  • Author(s): Kawakami M, Oka Y, Tsuboi A, Harada Y, Elisseeva OA, Furukawa Y, Tsukaguchi M, Shirakata T, Nishida S, Nakajima H, Morita S, Sakamoto J, Kawase I, Oji Y, Sugiyama H.
  • Journal Title: Int J Hematol 85 Pages: 426-9
  • Peer Reviewed
• [Journal Article] A phase I/II trial of a WT1 (Wilms' Tumor Gene) peptide vaccine in patients with solid malignancy: Safety assessment based on the phase I data. (2006)
  • Author(s): Morita S, Oka Y., Tsuboi A, Kawakami M, Maruno M, Izumoto S, Osaki T, Taguchi T, Ueda T, Myoui A, Nishida S, Shirakata T, Ohno S, Oji Y, Aozasa K, Hatazawa J, Udaka K, Yoshikawa H, Yoshimine T, Noguchi S, Kawase I, Nakatsuka S, Sugiyama H, Sakamoto J.
  • Journal Title: Japanese Journal of Clinical Oncology 36 Pages: 231-236
  • Peer Reviewed
• [Journal Article] Th1-biased humoral immune responses against Wilms tumor gene WT1 product in the patients with hematopoietic malignancies. (2005)
  • Author(s): Wu F, Oka Y, Tsuboi A, Elisseeva O. A, Nakajima H, Fujiki F, Masuda T, Murakami M, Yoshihara S, Ikegame K, Hosen N, Kawakami M, Nakagawa M, Kubota T, Soma T, Yamagami T, Tsukaguchi M, Ogawa H, Oji Y, Hamaoka T, Kawase I, Sugiyama H.
  • Journal Title: Leukemia 19 Pages: 268-274
  • Peer Reviewed
• [Journal Article] Generation of human tumor-specific, HLA class I-restricted Th1 and Tc1 cells by cell engineering with tumor peptide-specific T cell receptor genes. (2005)
  • Author(s): Tsuji T, Yasukawa M, Matsuzaki J, Ohkuri T, Chamoto K, Wakita D, Azuma T, Niiya H, Miyoshi H, Kuzushima K, Oka Y, Sugiyama H, Ikeda H, Nishimura T.
  • Journal Title: Blood 106 Pages: 470-476
  • Peer Reviewed
• [Journal Article] WT1(235), a ninemer peptide derived from Wilms' tumor gene product, is a candidate peptide for the vaccination of HLA-A*0201-positive patients with hematopoietic malignancies. (2005)
  • Author(s): Li Z, Oka Y, Tsuboi A, Masuda T, Tatsumi N, Kawakami M, Fujioka T, Sakaguchi N, Nakajima H, Fujiki F, Udaka K, Oji Y, Kawase I, Sugiyama H.
  • Journal Title: Int J Hematol 82 Pages: 458-459
  • Peer Reviewed
• [Presentation] グリベックとの併用によるCMLに対するWT1ペプチドワクチン免疫療法 (2009)
  • Author(s): 尾路祐介、岡芳弘、西田純幸、白方俊章、保仙直毅、坪井昭博、中島博子、村尾綾子、杉山治夫
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-25
• [Presentation] 骨髄異形成症候群における末梢血WT1mRNA発現と抗WT1抗体産生の臨床的意義 (2009)
  • Author(s): 田村秀人、緒方清行、横瀬紀夫、岩切理歌、大田雅嗣、坂巻壽、遠山薫、山下泰史、近藤麻加、兵働英也、中村恭子、尾路祐介、杉山治夫、壇和夫
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-24
• [Presentation] MDSに対するWT1ワクチン療法 (2009)
  • Author(s): 坪井昭博、岡芳弘、川上学、尾路祐介、保仙直毅、西田純幸、米谷昇、杉山治夫
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-24
• [Presentation] MDS-AMLに対しHLA-A*2402拘束性改変型WT1ペプチドワクチン療法を行い、長期間AMLの再発なく経過している1例 (2008)
  • Author(s): 西田純幸、川上学、坪井昭博、村尾綾子、宮井沙緒里、白方俊章、保仙直毅、尾路祐介、塚口真知子、岡芳弘、杉山治夫
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-11
• [Presentation] グリベックとの併用によるCMLに対するWT1ペプチドワクチン免疫療法 (2008)
  • Author(s): 尾路祐介、岡芳弘、西田純幸、白方俊章、保仙直毅、高橋和子、村尾綾子、中島博子、坪井昭博、杉山治夫
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-10
• [Presentation] グリベックとの併用によるCMLに対するWT1ペプチドワクチン免疫療法 (2008)
  • Author(s): 尾路祐介、白方俊章、岡芳弘、西田純幸、坪井昭博、保仙直毅、杉山治夫
  • Organizer: 第89回近畿血液学地方会
  • Place of Presentation: 大阪
  • Year and Date: 2008-06-21
• [Presentation] WT1ペプチドワクチン療法を行い (2008)
  • Author(s): 西田純幸、岡芳弘、坪井昭博、杉山治夫、川上学、塚口真知子
  • Organizer: 長期間AMLの再発なく経過しているMDS-AMLの1例、第89回近畿血液学地方会
  • Place of Presentation: 大阪
  • Year and Date: 2008-06-21
• [Presentation] WT1 peptide vaccination at very low-dose for myelodysplastic syndrome. (2007)
  • Author(s): Kawakami M, Oka Y, Tsuboi A, Harada Y, Elisseeva OA, Furukawa Y, Hayashi T, Nishida S, Shirakata T; Hosen N, Nakajima H, Yamagami T, Soma T, Oji Y, Sugiyama H.
  • Organizer: 3rd International Conference on WT1 in Human Malignancies
  • Place of Presentation: Berlin
  • Year and Date: 2007-09-19
• [Presentation] Co-administration of WT1 peptide vaccine and IFN-・enhances tumor rejection compared to the injection of WT1 peptide vaccine alone in a mouse model. (2007)
  • Author(s): Nakajima H, Oka Y, Tsuboi A, Oji Y, Sugiyama H.
  • Organizer: 3rd International Conference on WT1 in Human Malignancies
  • Place of Presentation: Berlin
  • Year and Date: 2007-09-19
• [Presentation] 分子再発後にWT1ワクチンを投与し長期寛解を維持している急性骨髄性白血病の3例 (2006)
  • Author(s): 尾路祐介, 坪井昭博, 西田純幸, 白方俊章, 杉山治夫, 岡芳弘, 川上学
  • Organizer: 第86回近畿血液学地方会
  • Place of Presentation: 和歌山
  • Year and Date: 2006-11-18
• [Presentation] 分子再発急性骨髄性白血病に対してWT1ペプチドワクチン療法施行し長期血液学的寛解を維持している3症例 (2006)
  • Author(s): 西田純幸、坪井昭博、岡芳弘、川上学、中島博子、OLGA ELISSEEVA、許泰一、杉山治夫
  • Organizer: 第68回日本血液学会総会・第48回日本臨床血液学会総会合同総会
  • Place of Presentation: 福岡
  • Year and Date: 2006-10-09
• [Presentation] WT1ペプチド癌ワクチン投与患者末梢血中のWT1特異的CTLの解析 (2006)
  • Author(s): 岡芳弘、OLGA ELISSEEBA、長谷浩志、川上学、西田純幸、白方俊章、原田ゆきえ、中島博子、李哲雨、藤木文博、尾路祐介、川瀬一郎、坪井昭博、杉山治夫
  • Organizer: 第68回日本血液学会総会・第48回日本臨床血液学会総会合同総会
  • Place of Presentation: 福岡
  • Year and Date: 2006-10-07
• [Presentation] 骨髄異形成症候群(MDS)に対する少量WT1ペプチド療法 (2006)
  • Author(s): 川上学、坪井昭博、西田純幸、白方俊章、原田ゆきえ、中島博子、藤木文博、李哲雨、OLGA ELISSEEVA、尾路祐介、古川佳央、林孝昌、岡芳弘、杉山治夫
  • Organizer: 第68回日本血液学会総会・第48回日本臨床血液学会総会合同総会
  • Place of Presentation: 福岡
  • Year and Date: 2006-10-07
• [Presentation] WT1 specific CTLs in WT1 peptide vaccine-treated patients (2005)
  • Author(s): Olga Elisseeva, Yoshihiro Oka, Akihiro Tsuboi, Hiroshi Hase, Hiroko Nakajima, Yukie Harada, Manabu Kawakami, Fumihiro Fujiki, Sumiyuki Nishida, Toshiaki Shirakata, Satoshi Oono, Ichirou Kawase, Yusuke Oji, Haruo Sugiyama
  • Organizer: The Second International Conference on WT1 in Human Neoplasia
  • Place of Presentation: Kyoto
  • Year and Date: 2005-10-22
• [Presentation] WT1-peptide vaccination for acute myeloid leukemia (2005)
  • Author(s): Manabu Kawakami, Yoshihiro Oka, Akihiro Tsuboi, Hiroko Nakajima, Olga A. Elisseeva, Hiroshi Hase, Yukie Harada, Fumihiro Fujiki, Zheyu LI, Tatsumi, Sumiyuki Nishida, Satoshi Ohno, Toshiaki Shirakata, Ichiro Kawase, Yusuke Oji, Haruo Sugiyama
  • Organizer: The Second International Conference on WT1 in Human Neoplasia
  • Place of Presentation: Kyoto
  • Year and Date: 2005-10-22
• [Presentation] Identification and characterization of a WT1 (Wilms' tumor gene) protein-derived HLA-DRB1*0405-restricted 16-mer helper peptide that promotes the induction and activation of WT1-specific cytotoxic T lymphocytes (2005)
  • Author(s): Fumihiro Fujiki, Yoshihiro Oka, Akihiro Tsuboi, Manabu Kawakami, Mai Kawakatsu, Hiroko Nakajima, Olga A. Elisseeva, Yukie Harada, Ken Ito, Zheyu Li, Naoya Tatsumi, Nao Sakaguchi, Tatsuya Fujioka, Tomoki Masuda, Masaki Yasukawa, Keiko Udaka, Yusuke Oji, Haruo Sugiyama
  • Organizer: The Second International Conference on WT1 in Human Neoplasia
  • Place of Presentation: Kyoto
  • Year and Date: 2005-10-21
• [Presentation] WT1 (Wilms'tumor Gene) Peptide-Based Cancer Immunotherapy (2005)
  • Author(s): Sugiyama H
  • Organizer: 10th JAPANESE-GERMAN WORKSHOP
  • Place of Presentation: Essen
  • Year and Date: 2005-10-01
• [Presentation] WT1ワクチンによる特異的細胞傷害性T細胞の解析 (2005)
  • Author(s): エリセーバ・オリガ, 長谷浩志, 坪井昭博, 岡芳弘, 杉山治夫
  • Organizer: 第64回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2005-09-16
• [Presentation] WT1特異的CD4*ヘルパーT細胞を誘導できるHLA-classII拘束性ペプチドの同定 (2005)
  • Author(s): 藤木文博, 岡芳弘, 坪井昭博, 川上学, 川勝真衣, 中島博子, オリガ・エリセーバ, 原田ゆきえ, 李哲雨, 伊藤憲, 宇高恵子, 尾路祐介, 杉山治夫
  • Organizer: 第64回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2005-09-16
• [Presentation] WT1ペプチドを用いた免疫療法 (2005)
  • Author(s): 杉山治夫
  • Organizer: 第9回基盤的癌免疫研究会総会
  • Place of Presentation: 東京
  • Year and Date: 2005-07-15
• [Presentation] Increase in numbers of antigen-experienced CD45RA+CD-CCR7+WT1-specific CTLs correlate with clinical response to WT1 vaccine (2005)
  • Author(s): エリセーバ・オリガ, 長谷浩志, 坪井昭博, 岡芳弘, 杉山治夫
  • Organizer: 第9回基盤的癌免疫研究会総会
  • Place of Presentation: 東京
  • Year and Date: 2005-07-15
• [Presentation] 骨髄異形成症候群(MDS)に対する少量WT1ペプチド療法 (2005)
  • Author(s): 川上学, 坪井昭博、原田ゆきえ, 中島博子, 白方俊章, 大野智, 藤木文博, 李哲雨, エリセーバ・オリガ, 尾路祐介, 古川佳央, 岡芳弘, 杉山治夫
  • Organizer: 第9回基盤的癌免疫研究会総会
  • Place of Presentation: 東京
  • Year and Date: 2005-07-15
• [Presentation] 少量WT1ペプチド療法により慢性骨髄単球性白血病(CMML)の進行が抑制された1例 (2005)
  • Author(s): 川上学, 坪井昭博, 西田純幸, 白方俊章, 岡芳弘, 尾路祐介, 杉山治夫, 古川佳央
  • Organizer: 第83回近畿血液学地方会
  • Place of Presentation: 大阪
  • Year and Date: 2005-06-11
• [Presentation] WT1ペプチドワクチン療法が奏効した多発性骨髄腫の1例 (2005)
  • Author(s): 坪井昭博, 川上学, 西田純幸, 中島博子, 岡芳弘, 白方俊章, 大野智, 尾路祐介, 杉山治夫
  • Organizer: 第83回近畿血液学地方会
  • Place of Presentation: 大阪
  • Year and Date: 2005-06-11
• [Presentation] WT1(Wilms' tumor gene) peptide-based immunotherapy for myelodysplastic syndrome (2005)
  • Author(s): Haruo Sugiyama, Akihiro Tsuboi, Manabu Kawakami Yusuke Oji, Yoshihiro Oka
  • Organizer: 8th International Symposium on Myelodysplastic Syndromes MDS 2005
  • Place of Presentation: 長崎
  • Year and Date: 2005-05-14
• [Remarks]
  • URL: http://sahswww.med.osaka-u.ac.jp/~hmtonc/index.html