Hemoglobin-beta1 as cancer antigen against GIST

2012 Fiscal Year Final Research Report

• Project/Area Number: 22700898
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Tumor immunology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: KOMITA Hideo 東京慈恵会医科大学, 医学部, 助教 (90534561)
• Project Period (FY): 2010 – 2012
• Keywords: GIST / Hemoglobin-beta1 / 周細胞 / Sutent

Research Abstract

Gastrointestinal stromal tumor (GIST) is the most common mesencymal tumor of the gastrointestinal tract. After surgical resection of primary tumor, tumor recurrence is frequent and 50% of patinets died within 5years of initial diagnosis. The KIT inhibitor imatinib mesylate is the reference treatment in the first line in advanced GISTs as adjuvant setting. However Imatinib mesylate is well tolerated in most patinets. Second line, Sunitinib malate is also similar situation.Recent results and reports suggest cancer vaccine treatment targeting the tumor-associated vasculature. CD8+T cells in regressor mice showed strong reactivity against HPLC eluted peptides (HBB1) by acid elution from surgical removed CMS4 lesions. In situimaging suggest GIST tumor vascular express HBB1 with pericyte markers(NG2, TEM1,RGS5,αSMA). TBVA vaccine against GIST should induce antipericyte Tc1 cells

Research Products

• [Journal Article] Vaccines targeting tumor blood vessel antigens promote CD8(+) T cell-dependent tumor eradication or dormancy in HLA-A2 transgenic mice. (2012)
  • Author(s): Zhao X, Bose A, Komita H, Taylor JL, Chi N, Lowe DB, Okada H, Cao Y, Mukhopahyay D, Cohen PA, Storkus WJ.
  • Journal Title: J Immunol. Volume: 188(4) Pages: 1782-1788
  • DOI: doi:10.4049/jimmunol. 1101644
• [Journal Article] Immunotherapy synergizes with chemotherapy targeting pancreatic cancer. (2012)
  • Author(s): Koido S, Homma S, Takahara A, Namiki Y, Komita H, Uchiyama K, Ito M, Gong J, Ohkusa T, Tajiri H
  • Journal Title: Immunotherapy. Volume: 4(1) Pages: 5-7
  • DOI: Doi:10.2217/imt.11.150
• [Journal Article] Current immunotherapeutic approaches in pancreatic cancer (2011)
  • Author(s): Koido S, Homma S, Takahara A, Namiki Y, Tsukinaga S, Mitobe J, Odahara S, Yukawa T, Matsudaira H, Nagatsuma K, Uchiyama K, Satoh K, Ito M, Komita H, Arakawa H, Ohkusa T, Gong J, Tajiri H
  • Journal Title: Clin Dev immunol Volume: 2011 Pages: 267539
  • DOI: Doi:10.1155/2011/267539
• [Journal Article] Gemcitabine enhances Wilms' tumor gene WT1 expression and sensitizes human pancreatic cancer cells with WT1-specific T-cell-mediated antitumor immune reponse (2011)
  • Author(s): Takahara A, Koido S, Ito M, Nagasaki E, Sagawa Y, Iwamoto T, Komita H, Ochi T, Fujiwara H, Yasukawa M, Mineno J, Shiku H, Nishida S, Sugiyama H, Tajiri H, Homma S.
  • Journal Title: Cancer Immunol Immunother Volume: 60(9) Pages: 1289-1297
  • DOI: Doi:10. 1007/s00262-011-1033-3
• [Journal Article] Immunologic monitoring of cellular responses by dendritic/tumor cell fusion vaccines. (2011)
  • Author(s): Koido S, Homma S, Takahara A, Namiki Y, Komita H, Nagasaki E, Ito M, Nagatsuma K, Uchiyama K, Satoh K, Ohkusa T, Gong J, Tajiri H.
  • Journal Title: J Biomed Biotechnol Volume: 2011 Pages: 910836
  • DOI: doi:10. 1155/2011/910836
• [Journal Article] Intratumoral Il-12 gene therapy results in the crosspriming of Tc1 cells reactive against tumor associated stromal antigens. (2011)
  • Author(s): Zhao X, Bose A, Komita H, Taylor JL, Kawabe M, Chi N, Spokas L, Lowe DB, Goldbach C, Alber S, Watkins SC, Butterfield LH, Kalinski P, Kirkwood JM, Storkus WJ
  • Journal Title: Mol Ther Volume: 19(4) Pages: 805-814
  • DOI: doi:10. 1038/mt.2010.295
• [Journal Article] [膵癌診療と研究の最先端] 進行膵癌に対するgemcitanbine併用WT1標的免疫療法の意義(解説/特集) (2011)
  • Author(s): 小井戸薫雄、本間定、高原映崇、込田英夫、大草敏史、田尻久雄
  • Journal Title: 胆と膵 Volume: 32(9) Pages: 887-891
• [Journal Article] Regulation of tumor immunity by tumor/dendritic cell fusions. (2010)
  • Author(s): Koido S, Homma S, Hara E, Namiki Y, Takahara A, Komita H,Nagasaki E, Ito M, Ohkusa T, Gong J, Tajiri H
  • Volume: 201
  • Pages: 516768.
  • DOI: doi:10.1155/2010/516768
• [Journal Article] Dendritic/pancreatic carcinoma fusions for clinical use: Comparative functional analysis of healthy-versus patient-derived fusions (2010)
  • Author(s): Koido S, Hara E, Homma S, Namiki Y, Komita H,Takahara A, Nagasaki E, Ito M, Sagawa Y, Mitsunaga M, Uchiyama K, Satoh K, Arihiro S, Ohkusa T, Gong J, Tajiri H.
  • Journal Title: Clin Immunol Volume: 135(3) Pages: 384-400
  • DOI: doi:10.1016/j-clim.2010.02.003
• [Presentation] 消化器癌の免疫学的解析と治療 腫瘍血管ペリサイトを標的とした新たながん免疫療法と GIST 治療への応用 (2012)
  • Author(s): 込田英夫、小井戸薫雄、本間定
  • Organizer: 日本消化器病学会雑誌109 巻臨時増総会pageA175
  • Year and Date: 20120300
• [Presentation] 膵癌に対するゲムシタビン併用 WT1 ペプチドワクチン療法の臨床効果と免疫誘導(Memory WT1-CTLs is a useful marker to predict the clinical outcome: WT1 vaccine in the combination with gemcitabine) (2011)
  • Author(s): 西田純幸、小井戸薫雄、原一馬、森本創世子、坪井昭博、本間定、武田裕、込田英夫、永野裕昭、岡芳弘、大草敏史、田尻久雄、杉山治夫
  • Organizer: 日本癌学会総会記事 70回page395
  • Year and Date: 20110900
• [Presentation] iPS 細胞から腫瘍血管を標的とした癌ワクチンの開発(Generation of a cancer vaccine targeting tumor vessel from iPS cells) (2011)
  • Author(s): 本間定、佐川由紀子、伊藤正紀、永崎栄次郎、高原映崇、込田英夫、小井戸薫雄
  • Organizer: 日本癌学会総会記事 70回 Page82
  • Year and Date: 20110900
• [Presentation] iPS 細胞から腫瘍血管を標的とした癌ワクチン療法の作製 (2011)
  • Author(s): 本間定、佐川由紀子、伊藤正紀、永崎栄次郎、高原映崇、込田英夫、小井戸薫雄
  • Organizer: 日本がん免疫学会総会プログラム 15回 Page105
  • Year and Date: 20110600
• [Presentation] 、WT1 ペプチドがん免疫療法の現状と将来膵がんに対する WT1 ペプチド免疫療法 (2010)
  • Author(s): 本間定、小井戸薫定、込田英夫、高原映崇、大草敏史、西田純幸、武田裕、岡芳弘、伊藤濤記、坪井昭博、杉山治夫
  • Organizer: 日本癌治療学会誌 45 巻 2 号 Page450
  • Year and Date: 20100900