Cancer antigen WT1-targeting peptide vaccine therapy for lung cancer

• Project/Area Number: 21590991
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Osaka University
• Principal Investigator: OKA Yoshihiro 大阪大学, 大学院・医学系研究科, 講師 (20273691)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Yoshito 大阪大学, 大学院・医学系研究科, 助教 (40452388)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: WT1 / 肺癌 / 癌免疫療法 / ペプチドワクチン / 免疫療法 / 胸腺腫

Research Abstract

We accumulated cases with lung cancer treated by WT1 peptide vaccine. We analyzed anti-WT1 antibody in nonsmall cell lung cancer patients, which showed the existence of immune response against WT1 protein in the lung cancer. We analyzed WT1-specific CTLs in bone marrow(BM) of cancer-bearing patients, which indicated the possibility that BM had a role as a secondary lymhpoid organ in cancer immunity. We analyzed WT1 helper peptide-specific response of CD4^+ T cells, which suggested an important role of Th response in cancer immunity. We demonstrated, using a mice model, that co-administration of WT1 peptide vaccine and IFN-βwas a promising novel therapy for cancer. Biased usage of TCR BV gene families of WT1-specific CD8^+ T cells in patients with solid tumors and healthy donors was shown.

Research Products

• [Journal Article] Biased usage of T cell receptorβ-chain variable region genes of WT1(Wilms' tumor gene)-specific CD8^+ T cells in patients with solid tumors and healthy donors (2012)
  • Author(s): Morimoto S., Oka Y., Tsuboi A., Tanaka Y., Fujiki F., Nakajima H., Hosen N., Nishida S., Nakata J., Nakae Y., Murao A., Myoui A., Enomoto T., Izumoto S., Sekimoto M., Kagawa N., Hashimoto N., Yoshimine T., Oji Y., Kumanogoh A., Sugiyama H
  • Journal Title: Cancer Science Volume: 103 Pages: 408-414
  • Peer Reviewed
• [Journal Article] Enhanced tumor immunity of WT1 peptide vaccination by interferon-βadministration (2012)
  • Author(s): Nakajima H., Oka Y., Tsuboi A., Tatsumi N., Yamamoto Y., Fujiki F., Li Z., Murao A., Morimoto S., Hosen N., Shirakata T., Nishida S., Kawase I., Isaka Y., Oji Y., Sugiyama H
  • Journal Title: Vaccine Volume: 30 Pages: 722-729
  • Peer Reviewed
• [Journal Article] Enhanced tumor immunity of WT1 peptide vaccination by interferon-β administration (2012)
  • Author(s): Nakajima H., et al
  • Journal Title: Vaccine Volume: 30 Issue: 4 Pages: 722-729
  • DOI: 10.1016/j.vaccine.2011.11.074
  • Peer Reviewed
• [Journal Article] Biased usage of T cell receptor β-chain variable region genes of Wilms' tumor gene (WT1)-specific CD8^+ T cells in patients with solid tumors and healthy donors (2012)
  • Author(s): Morimoto S., et al
  • Journal Title: Cancer Science Volume: 103 Issue: 3 Pages: 408-414
  • DOI: 10.1111/j.1349-7006.2011.02163.x
  • Peer Reviewed
• [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., Okuyama A., Kawase I., Oji Y., Sugiyama H
  • Journal Title: Anticancer Research Volume: 30 Pages: 2247-2254
  • Peer Reviewed
• [Journal Article] High frequencies of less differentiated and more proliferative WT1-specific CD8+ T cells in bone marrow in tumor-bearing patients : an important role of bone marrow as a secondary lymhpoid 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
  • Peer Reviewed
• [Journal Article] WT1 peptide vaccine, one of the most promising cancer vaccines : its present status and the future prospects. (2010)
  • Author(s): Oka Y., Sugiyama H.
  • Journal Title: Immunotherapy Volume: 2 Pages: 591-594
• [Journal Article] WT1 peptide vaccine induces reduction in minimal residual disease in an imatinib-treated CML patient. (2010)
  • Author(s): Oji Y., Oka Y., et al.
  • Journal Title: European Journal of Hematology Volume: 85 Pages: 358-360
  • Peer Reviewed
• [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., Oka Y., et al
  • Journal Title: Proceedings of the National Academy of Sciences of the USA Volume: 107 Pages: 13824-13829
  • Peer Reviewed
• [Journal Article] Prognostic significance of WT1 mRNA and anti-WT1 antibody levels inperipheral blood in patients with myelodysplastic syndromes. (2010)
  • Author(s): Tamura H., Oka Y., et al.
  • Journal Title: Leukemia Research Volume: 34 Pages: 986-990
  • Peer Reviewed
• [Journal Article] WT1 peptide immunotherapy for cancer in children and young adults (2010)
  • Author(s): Hshii Y., Oka Y., et al.
  • Journal Title: Pediatric Blood & Cancer Volume: 55 Pages: 352-355
  • Peer Reviewed
• [Journal Article] WT1 peptide vaccination in combination with imatinib therapy for apatient with CML in the chronic phase. (2010)
  • Author(s): Narita M., Oka Y., et al.
  • Journal Title: International Journal of Medical Sciences Volume: 7 Pages: 72-81
  • Peer Reviewed
• [Journal Article] Prognostic value of WT1 protein expression level and MIB-1 staining index as predictor of response to WT1 immunotherapy in glioblastoma patients. (2010)
  • Author(s): Chiba Y., Oka Y., et al.
  • Journal Title: Brain Tumor Pathology Volume: 27 Pages: 29-34
  • Peer Reviewed
• [Journal Article] Effects of concomitant temozolomide and radiation therapies on WT1-specific T cells in malignant glioma. (2010)
  • Author(s): Chiba Y., Oka Y., et al.
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 40 Pages: 395-403
  • Peer Reviewed
• [Journal Article] Sensitive immunohistochemical detection of WT1 protein in tumors with anti-WT1 antibody against WT1 235 peptide. (2010)
  • Author(s): Ichinohazama R., Oka Y., et al.
  • Journal Title: Cancer Science Volume: 101 Pages: 1089-1092
  • NAID: 10026591723
  • Peer Reviewed
• [Journal Article] High frequencies of less differentiated and more proliferative WT1-specific CD8+ T cells in bone marrow in tumor-bearing patients : an important role of bone marrow as a secondary lymphoid organ. (2010)
  • Author(s): Murao A., Oka Y., et al.
  • Journal Title: Cancer Science Volume: 101 Pages: 848-854
  • NAID: 10026590478
  • Peer Reviewed
• [Journal Article] WT1ペプチドがんワクチン (2010)
  • Author(s): 岡芳弘、坪井昭博, ら
  • Journal Title: 細胞 Volume: 42 Pages: 480-483
• [Journal Article] WT1 peptide vaccine as a paradigm for" cancer antigen-derived peptide"-based immunotherapy for malignancies : Successful induction of ant-cancer effect by vaccination with a single kind of WT1 peptide (2009)
  • Author(s): Oka Y., Tsuboi A., Fujiki F., Li Z., Nakajima H., Hosen N., Shirakata T., Nishida S., Oji Y., Kawase I., Sugiyama H
  • Journal Title: Anti-Cancer Agents in Medicinal Chemistry Volume: 9 Pages: 787-797
  • Peer Reviewed
• [Journal Article] WT1 IgG antibody for early detection of non-small cell lung cancer and as its prognostic factor (2009)
  • Author(s): Oji Y., Kitamura Y., Kamino E., Kitano A., Sawabata N., Inoue M., Mori M., Nakatsuka S-I., Sakaguchi N., Miyazaki K., Nakamura M., Fukuda I., Nakamura J., Tatsumi N., Takakuwa T., Nishida S., Shirakata T., Hosen N., Tsuboi A., Nezu R., Maeda H., Oka Y., Kawase I., Aozasa K., Okumura M., Miyoshi S., Sugiyama H
  • Journal Title: International Journal of Cancer Volume: 125 Pages: 381-387
  • Peer Reviewed
• [Journal Article] WT1 IgG antibody for early detection of nonsmall cell lung cancer as its prognostic factor (2009)
  • Author(s): Oji Y., Kitamura Y., et al
  • Journal Title: International Journal of Cancer 125 Pages: 381-387
  • Peer Reviewed
• [Journal Article] WT1 peptide vaccine as a paradigm for "cancer antigen-derived peptide" -based immunotherapy for malignancies : successful induction of anti-cancer effect by vaccination with a single kind of WT1 peptide (2009)
  • Author(s): Oka Y., Tsuboi A., et al
  • Journal Title: Anticancer Agents in Medicinal Chemistry 9 Pages: 787-797
  • Peer Reviewed
• [Journal Article] Wilms' tumor 1 (WT1) peptide immunotherapy for gynecological malignancy (2009)
  • Author(s): Ohno S., Kyo S., et al
  • Journal Title: Anticancer Research 29 Pages: 4779-4784
  • Peer Reviewed
• [Journal Article] WT1 IgG antibody for early detection of nonsmall cell lung cancer as its prognostic factor (2009)
  • Author(s): Oji Y., Kitamura Y., et al
  • Journal Title: International Journal of Cancer Volume: 125 Pages: 381-387
  • Peer Reviewed
• [Journal Article] WT1 peptide vaccine as a paradigm for “cancer antigen-derived peptide”-based immunotherapy for malignancies : successful induction of anti-cancer effect by vaccination with a single kind of WT1 peptide (2009)
  • Author(s): Oka Y., Tsuboi A., et al
  • Journal Title: Anticancer Agents in Medicinal Chemistry Volume: 9 Pages: 787-797
  • Peer Reviewed
• [Journal Article] Wilms' tumor1 (WT1) peptide immunotherapy for gynecological malignancy (2009)
  • Author(s): Ohno S., Kyo S., et al
  • Journal Title: Anticancer Research Volume: 29 Pages: 4779-4784
  • Peer Reviewed
• [Journal Article] High frequencies of less differentiated and more proliferative WT1-specific CD8 T cells in bone marrow in tumor-bearing patients : An important role of bone marrow as a secondary lymphoid organ
  • Author(s): Murao A., Oka Y., et al.
  • Journal Title: Cancer Science (in press)
  • NAID: 10026590478
  • Peer Reviewed
• [Journal Article] High frequencies of less differentiated and more proliferative WT1-specific CD8 T cells in bone marrow in tumor-bearing patients : Animportant role of bone marrow as a secondary lymphoid organ
  • Author(s): Murao A., Oka Y., et al.
  • Journal Title: Cancer Science
  • Description: in press
  • Peer Reviewed
• [Presentation] 腫瘍抗原WT1特異的ヒトTh17細胞クローンの樹立と機能解析/ Establishment and characterization of tumor antigen WT1-specific human Th17 clone (2011)
  • Author(s): Tachino S, Fujiki F., Oka Y., Tsuboi A., Nakajima H., Hosen N., Oji Y., Kumanogoh A., Sugiyama H
  • Organizer: 第40回日本免疫学会学術総会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] WT1 peptide vaccination combined with IFN-βenhances tumor rejection in a mice model (2011)
  • Author(s): Nakajima H., Oka Y., Tsuboi A., Tatsumi N., Fujiki F., Morimoto S., Hosen N., Shirakata T., Nishida S., Oji Y., Sugiyama H
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] WT1 peptide vaccination combined with IFN-β enhances tumor rejection in a mice model (2011)
  • Author(s): Nakajima H., et al
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] 膠芽腫に対するWT1ペプチドワクチン療法における長期生存例と予後予測因子 (2010)
  • Author(s): 橋本直哉、岡芳弘, ら
  • Organizer: 第23回バイオセラピィ学会学術集会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-12-09
• [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、岡芳弘, ら
  • Organizer: 第23回バイオセラピィ学会学術集会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-12-09
• [Presentation] WT1 peptide vaccine for the treatment of malignancies. Symposium 1(Cancer Immunotherapy : Current Status and Future Prospects) (2010)
  • Author(s): Oka Y, Sugiyama H
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-24
• [Presentation] MDSに対するWT1ペプチドワクチン療法第I相r臨床試験 (2010)
  • Author(s): 坪井昭博、岡芳弘, ら
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2010-09-24
• [Presentation] WT1 peptide vaccine for the treatment of malignancies (2010)
  • Author(s): Oka Y, Sugiyama H.
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜市(招待講演)
  • Year and Date: 2010-09-24
• [Presentation] A phase I study of WT1 peptide based cancer vaccine combined with gemcitabine for advanced pancreatic cancer (2010)
  • Author(s): Nishida S., Oka Y., ら
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-24
• [Presentation] 悪性グリオーマに対するWT1ワクチン療法;治療反応性予測因子としてのDTHとmethionine PET (2010)
  • Author(s): 橋本直哉、岡芳弘, ら
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-24
• [Presentation] WT1 peptide vaccine for the treatment of solid and hematological malignancies. Symposium 10(Cancer and Immunity) (2010)
  • Author(s): Oka Y, Sugiyama H
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] WT1 peptide vaccine for the treatment of solid and hematological malignancies (2010)
  • Author(s): Oka Y., Sugiyama H.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪市(招待講演)
  • Year and Date: 2010-09-22
• [Presentation] WT1 peptide immunotherapy has achieved long-term complete remission for the patients with acute myeloid leukemia with minimal residual disease (2010)
  • Author(s): Tsuboi A., Oka Y., ら
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-26
• [Presentation] Induction of complete and molecular repmissions in acute myeloid leukemia by Wilms'tumor 1 antigen-targeted dendritic cell vaccination (2010)
  • Author(s): Berneman Z.N., Oka Y., ら
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-26
• [Presentation] 担癌患者の骨髄中には末梢血に比較して癌抗原WT1特異的CD8^+ T細胞がより高頻度かつ未熟な状態で存在する (2010)
  • Author(s): 岡芳弘、村尾綾子、坪井昭博、田中ゆきえ、藤木文博、中島博子、西田純幸、保仙直毅、尾路祐介、杉山治夫
  • Organizer: 第14回日本がん免疫学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2010-07-22
• [Presentation] 担癌患者の骨髄中には末梢血に比較して癌抗原WT1特異的CD8+T細胞がより高頻度かつ未熟な状態で存在する (2010)
  • Author(s): 岡芳弘、村尾綾子, ら
  • Organizer: 第14回日本がん免疫学会総会
  • Place of Presentation: 熊本市
  • Year and Date: 2010-07-22
• [Presentation] ペプチドワクチン-WT1ペプチド癌ワクチンをモデルとして-.シンポジウム(「臓器移植の将来の展望-HLAの医療への関与-」 (2010)
  • Author(s): 岡芳弘
  • Organizer: 第8回日本組織適合性学会近畿地方会
  • Place of Presentation: 大阪
  • Year and Date: 2010-02-06
• [Presentation] WT1-specific CD4+ T cell response should be useful as the prediction marker for clinical efficacy of WT1 CTL epitope peptide vaccination (2009)
  • Author(s): 藤木文博, ら
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-03
• [Presentation] 進行膵臓癌に対するゲムシタビン併用WT1ペプチドワクチン療法 (2009)
  • Author(s): 西田純幸, ら
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-10-01
• [Presentation] WT-1 peptide vaccine (2009)
  • Author(s): 岡芳弘
  • Organizer: 14^<th> congress of the European Hematology Association
  • Place of Presentation: ベルリン (ドイツ)
  • Year and Date: 2009-06-07
• [Presentation] WT-1 peptide vaccine (2009)
  • Author(s): 岡 芳弘
  • Organizer: 14^<th> congress of the European Hematology Association
  • Place of Presentation: ベルリン(ドイツ)
  • Year and Date: 2009-06-07
  • Invited