Immunotherapy targeting tumor vascular cells using iPS cell-derived vaccine

2011 Fiscal Year Final Research Report

• Project/Area Number: 22650232
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Tumor immunology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: HOMMA Sadamu 東京慈恵会医科大学, 医学部, 准教授 (50192323)
• Co-Investigator(Kenkyū-buntansha): KOIDO Shigeo 東京慈恵会医科大学, 医学部, 准教授 (70266617) ; ITO Masaki 東京慈恵会医科大学, 医学部, 助教 (80297366)
• Project Period (FY): 2010 – 2011
• Keywords: iPS細胞 / 血管前駆細胞 / 腫瘍血管 / 血管新生 / 樹状細胞 / 血管内皮細胞 / 血管周細胞 / 抗腫瘍効果

Research Abstract

Induced Pluripotent Stem(iPS) cells are able to differentiate into vascular progenitor cells(iVP cells). Immunization of mice with dendritic cells pulsed with iVP cell lysate could induce potent antitumor immunity. Development of tumor vascular system was significantly suppressed and antibody against vascular endothelial cells was induced in the immunized mice. It is suggested that immunization with iVP cells could confer antitumor activity by induction of immune response against tumor vasculature.

Research Products

• [Journal Article] Clinical and immunologic evaluation of dendritic cell-based immunotherapy in combination with gemcitabine and/or S-1 in patients with advanced pancreatic carcinoma (2012)
  • Author(s): Takahashi H, Imai K, Shimamura K, Sunamura M, Yonemitsu Y, Shimodaira S, Koido S, Homma S, Okamoto M
  • Journal Title: Pancreas Volume: 41 Pages: 195-205
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Gemcitabine enhances Wilms' tumor gene WT1 expression and sensitizes human pancreatic cancer cells with WT1-specific T-cell-mediated antitumor immune response (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
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] 進行膵癌に対するGemcitabine併用WT1標的免疫療法の意義 (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 Pages: 887-891
  • Peer Reviewed
• [Journal Article] The identification of a novel Paneth cell-associated antigen in a familial adenomatous polyposis mouse model (2010)
  • Author(s): Ito M, Suzuki H, Sagawa Y, Homma S
  • Journal Title: Biochem Biophys Res Commun Volume: 400 Pages: 548-553
  • Peer Reviewed
• [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, and Tajiri H
  • Journal Title: Clin Dev Immunol Volume: Volume 2010 Pages: 14
  • Peer Reviewed
• [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 Pages: 384-400
  • Peer Reviewed
• [Journal Article] Antigen. specific polyclonal cytotoxic T lymphocytes induced by fusions of dendritic cells and tumor cells (2010)
  • Author(s): Koido S, Homma S, Hara E, Namiki Y, Okusa T, Gong J, Tajiri H
  • Journal Title: J Biomed Biotech Volume: Volume 2010 Pages: 12
  • DOI: doi:10.1155/2010/752381
  • Peer Reviewed
• [Journal Article] Accumulation of functional regulatory T cells in a actively inflamed liver in mouse dendritic cell-based autoimmune hepatic inflammation (2010)
  • Author(s): Saeki C, Nakano M, Takahashi H, Saito S, Homma S, Tajiri H, Zeniya M
  • Journal Title: Clin Immunol Volume: 135 Pages: 156-166
  • Peer Reviewed
• [Journal Article] Combined treatment with dendritic cells and 5-fluorouracil elicits augmented NK-cell. mediated antitumor activity via tumor necrosis factor-alpha pathway (2010)
  • Author(s): Nagasaki E, Takahara A, Koido S, Sagawa Y, Aiba K, Tajiri H, Yagita H, Homma S
  • Journal Title: J Immunother Volume: 33 Pages: 467-474
  • Peer Reviewed
• [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 (2012)
  • 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、永野浩昭、岡芳弘、大草敏史、田尻久雄、杉山治夫
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-10-05
• [Presentation] 化学療法剤による癌細胞の免疫感受性の増強 (2012)
  • Author(s): カンシン、木村幸乃、塚田旬、吉崎慎二、石田尾武文、岡本正人、本間定、小井戸薫雄、恒富亮一、吉村清、硲彰一、岡正朗
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-10-04
• [Presentation] iPS細胞から腫瘍血管を標的とした癌ワクチンの開発 (2012)
  • 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: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-10-03
• [Presentation] Activated NKT cells producing interferon-gamma potentiate cytotoxic T cell-mediated autoimmune hepatic inflammation (2011)
  • Author(s): Nakano M, Nakagawa R, Saeki C, Oikawa T, Takahashi H, Homma S, Zeniya M
  • Organizer: 59^<th> American Association of Liver disease Liver Meeting
  • Place of Presentation: San Francisco
  • Year and Date: 2011-11-07
• [Presentation] iPS細胞から腫瘍血管を標的とした癌ワクチンの作製 (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: 第15回日本がん免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2011-07-01
• [Presentation] 自己免疫性肝障害を惹起する自己反応性CD8+T細胞の活性化と肝内誘導には肝内活性化NKT細胞が関与する (2011)
  • Author(s): 中野真範、中川良、佐伯千里、及川恒一、高橋宏樹、本間定、田尻久雄、銭谷幹男
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-03
• [Presentation] 膵癌に対するWT1ペプチド免疫療法 (2010)
  • Author(s): 本間定、小井戸薫雄、込田英夫、高原映崇、大草敏史、西田純幸、武田裕、岡芳弘、伊藤壽記、坪井昭博、杉山治夫
  • Organizer: 第48回日本癌治療学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-29
• [Presentation] 切除不能・再発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第1相臨床試験 (2010)
  • Author(s): 西田純幸、武田裕、小井戸薫雄、岡芳弘、込田英夫、本間定、大草敏史、森正樹、土岐祐一郎、川瀬一郎、田尻久雄、杉山治夫
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] 臨床応用に向けた樹状細胞と膵癌細胞との融合膵癌ワクチン (2010)
  • Author(s): 小井戸薫雄、本間定、込田英夫、高原映崇、大草敏史、田尻久雄
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] 抗腫瘍免疫反応により産生されるインターフェロンガンマはゲムシタビン活性化酵素の発現を上昇させる (2010)
  • Author(s): 本間定、佐川由紀子、高原映崇、永崎栄次郎、込田英夫、伊藤正紀、小井戸薫雄
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] 進行膵癌に対するWT1ペプチドワクチンと塩酸ゲムシタビンの併用効果のメカニズム (2010)
  • Author(s): 本間定、高原映崇、小井戸薫雄
  • Organizer: 第19回日本癌病態治療研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-01
• [Presentation] 進行膵癌に対するWT1ペプチドワクチンと塩酸ゲムシタビンの併用効果のメカニズム (2010)
  • Author(s): 本間定、高原映崇、小井戸薫雄
  • Organizer: 日本消第96回化器病学会総会
  • Place of Presentation: 新潟
  • Year and Date: 2010-04-22