Development of WT1 based immunotherapy after stem cell transplantation and the analysis of antitumor activity

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591160
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Osaka University
• Principal Investigator: HASHII Yoshiko 大阪大学, 医学系研究科, 講師 (60343258)
• Co-Investigator(Kenkyū-buntansha): OKA Yoshihiro 大阪大学, 大学院・医学絵系研究科, 講師 (20273691) ; OHTA Hideaki 大阪大学, 大学院・医学絵系研究科, 講師 (60322187) ; MIYASHITA Emiko 大阪大学, 大学院・医学絵系研究科, 助教 (40528395)
• Project Period (FY): 2010 – 2012
• Keywords: 小児腫瘍学 / 癌ワクチン

Research Abstract

Wilms tumor gene, WT1, is highly expressed in hematological malignancy. The gene product (WT1 protein) could be a good target antigen for immunotherapy against leukemia. We started the clinical trial of WT1 peptide vaccination after stem cell transplantation with high risk hematological malignancy from 2010. 18 pediatric patients had been enrolled and 13 patients maintained complete remission. The number of WT1 specific cytotoxic T lymphocytes were increased in these patientswith remission. Our results highlight the potential of WT1 vaccination to boost the GVL effect.

Research Products

• [Journal Article] WT1 peptide immunotherapy for gynecologic malignancies resistant to conventional therapies: a phase II trial (2013)
  • Author(s): Miyatake T., Ueda Y., Morimoto A., Enomoto T., Nishida S., Shirakata T., Oka Y., Tsuboi A., Oji Y., Hosen N., Nakatsuka S-I., Morita S., Sakamoto J., Sugiyama H., Kimura T.
  • Journal Title: Jounal of Cancer Research and Clinical Oncology Volume: 139 Pages: 457-463
• [Journal Article] Identification of a Wilms' tumor 1 (WT1)-derived immunogenic CD4+ T-cell epitope that is recognized in the context of common Caucasian HLA-DR haplotypes (2013)
  • Author(s): Anguille S., Fujiki F., Smits E.L., Oji Y., Lion E., Oka Y., Berneman Z.N., Sugiyama H.
  • Journal Title: Leukemia Volume: 27 Pages: 748-750
• [Journal Article] WT1 peptide vaccination following allogeneic stem cell transplantation in pediatric leukemic patients with high risk for relapse: successful maintenance of durable remission (2012)
  • Author(s): Hashii Y, Sato-Miyashita E, Matsumura R, Kusuki S, Yoshida H, Ohta H, Hosen N, Tsuboi A, Oji Y, Oka Y, Sugiyama H, Ozono K
  • Journal Title: Leukemia Volume: 26 Pages: 530-532
• [Journal Article] A vaccine for leukemia -one step closer? Cure-oriented WT1 peptide vaccination therapy is being developed (2012)
  • Author(s): Oka Y
  • Journal Title: (Editorial) Clinical Investigation Volume: 3 Pages: 421-424
• [Journal Article] CD138-negative clonogenic cells are plasma cells but not B cells in some multiple myeloma patients (2012)
  • Author(s): Hosen N., Matsuoka Y, Kishida S., Nakata J., Mizutani Y., Hasegawa K., Mugitani A., Ichihara H., Aoyama Y., Nishida S., Tsuboi A., Fujiki F., Tatsumi N., Nakajima H., Hino M., Kimura T., Yata K., Abe M., OkaY., Oji Y., Kumanogoh A., Sugiyama H
  • Journal Title: Leukemia Volume: 26 Pages: 2135-41
  • Peer Reviewed
• [Journal Article] Long-term WT1 peptide vaccination for patients with minimal residual disease (2012)
  • Author(s): Tsuboi A., Oka Y., Kyo T., Katayama Y., Elisseeva O.A., Kawakami M., Nishida S., Morimoto S., Murao A., Nakajima H., Hosen N., Oji Y
  • Journal Title: Leukemia Volume: 26 Pages: 1410-1413
• [Journal Article] 同種造血幹細胞移植後の難治性小児血液腫瘍患者におけるWT1ペプチドワクチンを用いた免疫療法 (2011)
  • Author(s): 橋井佳子、松村梨沙、吉田寿雄、宮下恵実子、太田秀明、坪井昭博、尾路祐介、保仙直毅、岡 芳弘、大薗恵一、杉山治夫
  • Journal Title: Biotherapy Volume: 25 Pages: 851-856
• [Journal Article] 悪性腫瘍に対するWT1ペプチドワクチン療法-特に (2011)
  • Author(s): Oka Y, Tsuboi A, Nishida S, Hosen N, Nakata J, Hashii Y, Maeda T, Oji Y, Kumanogoh A, Sugiyama H
  • Journal Title: 造血器腫瘍に焦点を当て Volume: 52 Pages: 235-242
• [Journal Article] WT1 Peptide Immunotherapy for Cancer in Children and Young Adults (2010)
  • Author(s): Yo shi ko Ha shi i, Emiko Sato, Hideaki Ohta, Yoshihiro Oka, Haruo Sugiyama, keiichi Osono.
  • Journal Title: Pediatr Blood Cancer Volume: 55 Pages: 352-355
• [Journal Article] 小児がんに対するWT1ペプチドワクチン療法 (2010)
  • Author(s): 太田秀明、橋井佳子
  • Journal Title: 小児がん Volume: 47 Pages: 263-267
• [Journal Article] WT1 vaccine induces reduction in minimal residual disease in an imatinib-treated CML patient (2010)
  • Author(s): Oji Y., Oka Y., Nishida S., Tsuboi A., Kawakami M., Shirakata T., Takahashi K., Murao A., Nakajima H., Narita M., Takahashi M., Morita S., Sakamoto J., Tanaka T., Kawase I., Hosen N., Sugiyama H.
  • Journal Title: European Journal of Hematology Volume: 85 Pages: 358-360
• [Journal Article] Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination (2010)
  • Author(s): Van Tendeloo V.F., Van de Velde A., Van Driessche A., Cools N., Anguille S., Price D.A., Vermeulen K., Pieters K., Nijs G., Stein B., Smits E.L., Schroyens W.A., Gadisseur A. P., Vrelust I., Jorens P.G., Goossens H., de Vries I.J., Oji Y., Oka Y., Sugiyam
  • Journal Title: Proceedings of the National Academy of Sciences of the USA(PNAS) Volume: 107 Pages: 13824-13829
• [Journal Article] WT1 peptide vaccination in combination with imatinib therapy for a patient with CML in the chronic phase (2010)
  • Author(s): Narita M., Masuko M., Kurasaki T., Kitajima T., Takenouchi S., Saitoh A., Watanabe N., Furukawa T., Toba K., Fuse I., Aizawa I., Kawakami M., Oka Y., Sugiyama H., Takahashi M
  • Journal Title: International Journal of Medical Sciences Volume: 7 Pages: 72-81
• [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.A., Nishida S., Shirakata T., Hosen H., Fujiki F., Murao N., Nakajima H., Oji Y., Kanda Y., Kawase I., Sugiyama H
  • Journal Title: Cancer Science Volume: 101 Pages: 594-600
• [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., Ohyama K., Kondo A., Hyodo H., Nakamura K., Yamashita T., Elisseeva O. A., Oka Y., Oji Y., Sugiyama H., Ogata K
  • Journal Title: Leukemia Research Volume: 34 Pages: 986-990
• [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 O.A., 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 Volume: 101 Pages: 848-854
• [Journal Article] A clear correlation between WT1-specific Th response and clinical response in WT1 CTL epitope vaccination. (2010)
  • Author(s): Fujiki F., Oka Y., Kawakatsu M., Tsuboi A., Harada Y., Hosen N., Nishida S., Shirakata T., Nakajima H., Tatsumi N., Hashimoto N., Taguchi T., Ueda S., Nonomura N., takeda Y., Ito T., Myoui A., Izumoto Izumoto S., Maruno M., Yoshimine T., Noguchi S., Okuya
  • Journal Title: Anticancer Research Volume: 30 Pages: 2247-2254
• [Journal Article] HLA-DRB1*05:01-restricted WT1332-specific TCR-transduced CD4+ T lymphocytes display a helper activity for WT1-specific CTL induction and a cytotoxicity against leukemia cells.
  • Author(s): Lin Y., Fujiki F., Katsuhara A., Oka Y., Tsuboi A., Aoyama N., Tanii S., Nakajima H., Tatsumi N., Morimoto S., Tamanaka T., Tachino S., Hosen N., Nishida S., Oji Y., Kumanogoh A., Sugiyama H.
  • Journal Title: Journal of Immunotherapy
• [Presentation] 小児血液腫瘍に対する同種造血幹細胞移植後WT1ペプチドワクチンの有効性 (2013)
  • Author(s): 橋井佳子
  • Organizer: 第16回WT1ペプチド癌免疫療法研究会
  • Place of Presentation: 大阪
  • Year and Date: 2013-03-30
• [Presentation] がん抗原ペプチドを用いたワクチン治療の原理・現況・将来展望 -WT1ペプチドがんワクチンをそのモデルとして- シンポジウム(招待) (2013)
  • Author(s): 岡 芳弘、杉山治夫
  • Organizer: 第11回日本組織適合性学会近畿地方会
  • Place of Presentation: 大阪.
  • Year and Date: 2013-02-02
• [Presentation] Biased usage of T cell receptor β-chain variable region genes of cancer antigen WT1-specific CTLs in patients with solid tumors and healthy donors (2012)
  • Author(s): Morimoto S., Oka Y., Tsuboi A., Fujiki F., Nakajima H., Hosen N., Oji Y., Kumanogoh A., Sugiyama H
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] Cancer antigen WT1-specific helper and suppressive Th17 derived from a single precursor cell (2012)
  • Author(s): Tachino S, Oka Y, Fujiki F, Tsuboi A, Tamanaka T, Kondo K, Hosen N, Oji Y, Kumanogoh A, Sugiyama H
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] WT1 peptide vaccination following allogeneic stem cell transplantation in pediatric patients (2012)
  • Author(s): Yo shi ko Hshi i, Takako Miyamura, Risa Matsumura, Hisao Yoshida, Emiko Miyashita, Akihiro Tsuboi, Yusuke Oji, Naoki Hosen, Yoshihiro Oka, keiichi Ozono, Haruo Sugiyama
  • Organizer: The 6th International Conference on WT1 In Human Neoplasia
  • Place of Presentation: 京都
  • Year and Date: 2012-11-23
• [Presentation] chair person with Z. N. Bernemann, Section VI: Immunotherapy II: Clinical trials in solid cancers (2012)
  • Author(s): Yo shi hi ro Oka
  • Organizer: in The 6th International Conference on WT1 in Human Neoplasia
  • Place of Presentation: 京都
  • Year and Date: 2012-11-23
• [Presentation] Wilms tumor 1 (WT1) peptide vaccine as an enhancer of graft versus leukemia effects. (2012)
  • Author(s): Hosen N., Maeda T., Fukushima K., Morimoto S., Nakata J., Nakae Y., Takashima S., Nakajima H., Fujiki F., Tatsumi N., Nishida S., Tsuboi A., Kondo T., Hino M., Oji Y., Oka Y., Kumanogoh A., Sugiyama H
  • Organizer: The 6th International Conference on WT1 in Human Neoplasia
  • Place of Presentation: 京都
  • Year and Date: 2012-11-23
• [Presentation] HLA class II-restricted WT1332-specific TCR-transduced CD4+ T lymphocytes display a helper activity for WT1-specific CTL induction and a cytotoxicity against leukemia cells (2012)
  • Author(s): Lin Y., Fujiki F., Katsuhara A., Oka Y., Tsuboi A., Aoyama N., Tanii S., Nakajima H., Tatsumi N., Morimoto S., Tamanaka T., Tachino S., Hosen N., Nishida S., Oji Y., Kumanogoh A., Sugiyama H
  • Organizer: The 6th International Conference on WT1 in Human Neoplasia
  • Place of Presentation: 京都
  • Year and Date: 2012-11-23
• [Presentation] International harmonization on immunohistochemical evaluation of WT1 positivity in solid cancers. (2012)
  • Author(s): Oji Y., Berneman Z.N., Keilholz U., O'Reilly R., Saglio G., Wagner N., Heike Y., Lundin E., Morii E., Pauwells P., Pappotti M., Anguille S., Cilloni D., Letsch A., Ohashi H., Ohno Y., Waelput W., Duregon E., Hiraoka N., Udaka K., Izumoto S., Ohno S., Iwaf
  • Organizer: The 6th International Conference on WT1 in Human Neoplasia
  • Place of Presentation: 京都
  • Year and Date: 2012-11-23
• [Presentation] Haruo Sugiyama, Keiichi Oaono (2012)
  • Author(s): Yo shi ko Hshi i, Takako Miyamura, Risa Matsumura, Hisao Yoshida, Emiko Miyashita, Akihiro Tsuboi, Yusuke Oji, Naoki Hosen, Yoshihiro Oka
  • Organizer: 第74回日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-21
• [Presentation] 再発ハイリスク同種造血幹細胞移植後患者に対するWT1ペプチドワクチン第1相臨床試験. (2012)
  • Author(s): 保仙直毅、前田哲生、福島健太郎、森本創世子、中田 潤、中江吉希、西田純幸、坪井昭博、近藤忠一、門脇則光、日野雅之、尾路祐介、岡 芳弘、熊ノ郷淳、金倉 譲、杉山治夫.
  • Organizer: 第74回日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-19
• [Presentation] Cancer vaccine therapy and patients' quality of life, cover-makeup for unsightly skin reaction. (2012)
  • Author(s): 分田貴子、西田純幸、坪井昭博、保仙直毅、尾路祐介、梅田智恵、種村 篤、片山一郎、岡 芳弘、杉山治夫、平家勇司
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-21
• [Presentation] WT1 immunohistochemical staining and evaluation of WT1 positivity in solid cancers. (2012)
  • Author(s): 尾路祐介、福田菜莉、森井英一、辰己直也、北条 望、村上由衣、斉藤千紗恵、鈴木望友、川田紗世、澄川美穂子、坪井昭博、岡 芳弘、杉山治夫
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌.
  • Year and Date: 2012-09-21
• [Presentation] Phase II trial of WT1 peptide vaccine to gynecologic malignancies which are resistant to conventional chemotherapy. (2012)
  • Author(s): 森本晶子、上田 豊、宮武 崇、榎本隆之、岡 芳弘、西田純幸、坪井昭博、白方俊章、尾路祐介、森田智視、坂本純一、杉山治夫、木村 正
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌.
  • Year and Date: 2012-09-21
• [Presentation] WT1ペプチドワクチンを用いた小児血液腫瘍に対する同種造血幹細胞移植後免疫療法. (2012)
  • Author(s): 橋井佳子、宮村能子、松村梨紗、吉田寿雄、宮下恵実子、平松英文、谷澤昭彦、坪井昭博、尾路祐介、保仙直毅、岡 芳弘、杉山治夫、.大薗恵一
  • Organizer: 第4回造血器腫瘍免疫療法研究会学術総会
  • Place of Presentation: 金沢
  • Year and Date: 2012-08-18
• [Presentation] WT1ヘルパーペプチド投与による抗腫瘍免疫反応の増強 マウスモデルを用いた検討 (2012)
  • Author(s): 中島博子、岡 芳弘、坪井昭博、藤木文博、辰巳直也、尾路祐介、杉山治夫
  • Organizer: 第4回造血器腫瘍免疫療法研究会学術総会
  • Place of Presentation: 金沢
  • Year and Date: 2012-08-18
• [Presentation] 再発ハイリスク同種造血幹細胞移植患者に対するWT1ペプチドワクチン第1相臨床試験 (2012)
  • Author(s): 保仙直毅、前田哲生、福島健太郎、近藤忠一、日野雅之、岡 芳弘、熊ノ郷淳、金倉 譲、杉山治夫
  • Organizer: 第4回造血器腫瘍免疫療法研究会学術総会
  • Place of Presentation: 金沢
  • Year and Date: 2012-08-18
• [Presentation] 慢性期CMLに対するイマチニブ併用WT1ペプチドワクチン免疫療法 (2012)
  • Author(s): 尾路祐介、岡 芳弘、坪井昭博、保仙直毅、西田純幸、中田 潤、中江吉希、中島博子、藤木文博、辰巳直也、杉山治夫
  • Organizer: 第4回造血器腫瘍免疫療法研究会学術総会
  • Place of Presentation: 金沢
  • Year and Date: 2012-08-18
• [Presentation] 再発ハイリスク同種造血幹細胞移植後患者に対するWT1ペプチドワクチン第1相臨床試験 (2012)
  • Author(s): 保仙直毅、前田哲夫、福島健太郎、近藤忠一、日野雅之、岡 芳弘、熊ノ郷 淳、金倉 譲、杉山治夫.
  • Organizer: 第16回日本がん免疫学会総会
  • Place of Presentation: 札幌.
  • Year and Date: 2012-07-28
• [Presentation] 小児血液悪性腫瘍を対象とした同種造血幹細胞移植後のWT1ワクチン療法 (2012)
  • Author(s): 橋井佳子、大薗恵一
  • Organizer: 第15回WT1ペプチド癌免疫治療研究会
  • Place of Presentation: 大阪
  • Year and Date: 2012-03-31
• [Presentation] WT1ペプチドワクチンを用いた小児血液腫瘍に対する同種造血幹細胞移植後免疫療法 (2011)
  • Author(s): 橋井佳子
  • Organizer: 第70回日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] 同種造血幹細胞移植後のWT1ペプチドワクチンによる免疫療法 (2011)
  • Author(s): 橋井佳子
  • Organizer: 第14回WT1ペプチドがん免疫療法研究会
  • Place of Presentation: 大阪
  • Year and Date: 2011-09-10
• [Presentation] 同種造血幹細胞移植後のWT1ペプチドワクチンによる免疫療法 (2011)
  • Author(s): 橋井佳子
  • Organizer: 第3回造血器腫瘍免疫治療研究会
  • Place of Presentation: 別府
  • Year and Date: 2011-08-21
• [Presentation] 同種造血幹細胞移植後の難治性小児血液腫瘍患者に対する WT1 ペプチドワクチンを用いた免疫療法 (2010)
  • Author(s): 橋井佳子、太田秀明、松村梨沙、吉田寿雄、楠木重範、佐藤恵実子、坪井昭博、尾路祐介、岡 芳弘、杉山治夫、大薗恵一
  • Organizer: 第52回日本小児血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-19
• [Presentation] 同種造血幹細胞移植後の難治性小児血液腫瘍患者に対するWT1ペプチドワクチンを用いた免疫療法 (2010)
  • Author(s): 橋井佳子
  • Organizer: 日本バイオセラピイ学会
  • Place of Presentation: 大阪国際会議場.
  • Year and Date: 2010-12-09
• [Presentation] WT1ペプチドワクチンによる再発させない小児がん治療 (2010)
  • Author(s): 橋井佳子
  • Organizer: 第48回日本癌治療学会
  • Place of Presentation: 国立京都国際会議場.
  • Year and Date: 2010-10-29
• [Presentation] 同種造血幹細胞移植後の難治性小児血液腫瘍患者に対するWT1ペプチドワクチンを用いた免疫療法 (2010)
  • Author(s): 橋井佳子
  • Organizer: 第2回造血器腫瘍免疫治療研究会
  • Place of Presentation: 松山
  • Year and Date: 2010-08-28
• [Presentation] 小児血液腫瘍に対する同種造血幹細胞移植後のWT1ペプチドワクチン療法 (2010)
  • Author(s): 橋井佳子、松村梨沙、吉田寿雄、楠木重範、佐藤恵実子、太田秀明、大薗恵一
  • Organizer: 第12回WT1ペプチドがん免疫療法研究会
  • Place of Presentation: 大阪
  • Year and Date: 2010-07-10
• [Remarks]
  • URL: http://blogs.yahoo.co.jp/arekenped