Studies on generation of peptide vaccine against cancer stem cells of pancreatic cancer using proteomic analysis

• Project/Area Number: 20390214
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: HOMMA Sadamu Jikei University School of Medicine, 医学部, 准教授 (50192323)
• Co-Investigator(Kenkyū-buntansha): 小井戸 薫雄 東京慈恵会医科大学, 医学部, 准教授 (70266617) ; 伊藤 正紀 東京慈恵会医科大学, 医学部, 助教 (80297366)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2010: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 膵癌 / ペプチドワクチン / プロテオーム / 癌幹細胞 / 樹状細胞

Research Abstract

We have tried to identify cancer stem cell-specific antigenic peptide from dendritic cells (DCs) loaded with side-population (SP-population) of human pancreatic cancer cells. DCs pulsed with lysate of SP-fraction or non-SP-fraction of Panc-1 cells were treated with an adequate detergent and MHC class-I/antigenic peptide complex was isolated from these DCs using anti-HLA-A02 affinity column chromatography. The several specific peptides only from DCs loaded with SP-fraction were obtained. The isolated peptide is now being analyzed for identification of a possible candidate for peptide vaccine against cancer stem cells of human pancreatic cancer.

Research Products

• [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. 33 Pages: 467-474
• [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, et al.
  • Journal Title: Clin Immunol. 135 Pages: 156-166
• [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,, et al.
  • Journal Title: J Biomed Biotech. 2010
• [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, et al.
  • Journal Title: Clin Immunol. 135 Pages: 384-400
• [Journal Article] Regulation of Tumor Immunity by Tumor/Dendritic Cell Fusions. (2010)
  • Author(s): Koido S, Homma S, Hara E, et al.
  • Journal Title: Clin Dev Immunol. 2010
• [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. 400 Pages: 548-553
• [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, et al.
  • Journal Title: Clin Dev Immunol. Volume: 2010 Pages: 516768-516768
  • 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, et al.
  • 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, et al.
  • Journal Title: J Biomed Biotech. Volume: 2010 Pages: 752381-752381
  • 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, et al.
  • 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
• [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. 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-alphapathway (2010)
  • Author(s): Nagasaki E, Takahara A, Koido S, Sagawa Y, Aiba K, Tajiri H, Yagita H, Homma S.
  • Journal Title: J Immunother. (In press)
  • 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, et al.
  • Journal Title: Clin Immunol. (In press)
  • Peer Reviewed
• [Journal Article] Antigenic stimulation with cytochrome P450 2J expressed in mouse hepatocellular carcinoma cells regulates host anti-tumour immunity. (2009)
  • Author(s): Homma S, Koido S, Sagawa Y, et al.
  • Journal Title: Clin Exp Immunol. 156(2) Pages: 344-52
• [Journal Article] Antigenic stimulation with cytochrome P450 2J expressed in mouse hepatocellular carcinoma cells regulates host anti-tumor immunity (2009)
  • Author(s): Homma S, Koido S, Sagawa Y, et al.
  • Journal Title: Clinical and Experimental Immunology 156 Pages: 344-352
  • Peer Reviewed
• [Journal Article] In vitro generation of cytotoxic and regulatory T cells by fusions of human dendritic cells and hepatocellular carcinoma cells. (2008)
  • Author(s): Koido S, Homma S, Hara E, et al.
  • Journal Title: J Transl Med. 6 Pages: 51-70
• [Journal Article] In vitro generation of cytotoxic and regulatory T cells by fusions of human dendritic cells and hepatocellular carcinoma cells (2008)
  • Author(s): Koido S, Homma S, Hara E, et al.
  • Journal Title: Journal of Translational Medicine 6 Pages: 51-70
  • Peer Reviewed
• [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、ほか
  • 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] 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] 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、ほか
  • 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] 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、ほか
  • 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
• [Presentation] 膵癌に対するWT1ペプチドワクチンと塩酸ゲムシタビン併用療法の相乗効果のメカニズム (2009)
  • Author(s): 高原映崇, 永崎栄次郎, 小井戸薫雄, 佐川由紀子, 伊藤正紀, 越智俊元, 藤原弘, 安川正貴, 田尻久雄, 本間定
  • Organizer: 第22回日本バイオセラピィ学会学術集会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-11-27
• [Presentation] Accumulation of functional regulatory T cells in actively inflamed liver in mouse dendritic cell-based autoimmune hepatic inflammation. (2009)
  • Author(s): Chisato Saeki, Masanori Nakano, Tsunegazu oikawa, Hiroki Takahashi, Sadamu Homma, et al.
  • Organizer: The 60th Annual Meeting of the American Association for the Study of Liver Disease.
  • Place of Presentation: Boston
  • Year and Date: 2009-10-21
• [Presentation] 進行肝細胞癌における樹状細胞ワクチンの免疫回避機構の解明 (2009)
  • Author(s): 小井戸薫雄, 本間定, 込田英夫, ほか
  • Organizer: 第51回日本消化器病学会大会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-15
• [Presentation] Conditional IL-12 Gene Therapy Promotes Safe amd effective Anti-Tumor Immunity. (2009)
  • Author(s): 込田英夫, 小井戸薫雄, 本間定, ほか
  • Organizer: 第51回日本消化器病学会大会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-15
• [Presentation] 樹状細胞と5-FUの併用療法はTNF-αを介した抗腫瘍効果. (2009)
  • Author(s): 永崎栄次郎, 小井戸薫雄, 田尻久雄, 相羽恵介, 本間定
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Presentation] 肝細胞癌産生物質はヒト樹状細胞と癌細胞との融合細胞を未成熟化し抑制性T細胞を誘導する (2009)
  • Author(s): 小井戸薫雄, 本間定, 原栄一, 込田英夫, 佐川由紀子, 高原映崇, 永崎栄二郎, 伊藤正紀, ほか
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Presentation] On/offシステムによるIL-12遺伝子治療により安全で効率的な抗腫瘍効果の誘導 (2009)
  • Author(s): 込田英夫, Xi Zhao, 小井戸薫雄, 本間定, ほか
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Presentation] 肝細胞癌産生物質はヒト樹状細胞と癌細胞との癒合細胞を未熟化し抑制性T細胞を誘導する (2009)
  • Author(s): 小井戸薫雄、本間定、原栄一、込田英夫、並木禎尚, ほか
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] 樹状細胞と5-FUの併用療法はTNF-αを介した抗腫瘍相乗効果を示した (2009)
  • Author(s): 永崎栄次郎、高原映崇、小井戸薫雄、田尻久雄、本間定, ほか
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [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, 武田裕, 岡芳弘, 小井戸薫雄, 込田英夫, 伊藤壽記, 本間定, ほか
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] 膵癌に対するWT1ペプチドワクチンと塩酸ゲムシタビン併用療法の相乗効果のメカニズム (2009)
  • Author(s): 高原映崇, 永崎栄二郎, 小井戸薫雄, 佐川由紀子, 伊藤正紀, 田尻久雄, 本間定
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] WT1ペプチドワクチンと塩酸ゲムシタビンを併用した進行膵臓癌に対する新たな治療戦略 (2009)
  • Author(s): 西田純幸, 武田裕, 岡芳弘, 小井戸薫雄, 本間定, ほか
  • Organizer: 第13回日本がん免疫学会総会
  • Place of Presentation: 北九州
  • Year and Date: 2009-06-25
• [Presentation] 肝血管肉腫に対する抗腫瘍免疫の誘導 (2009)
  • Author(s): 込田英夫, 本間定, 小井戸薫雄, ほか
  • Organizer: 第45回肝臓病学、会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-05
• [Presentation] 肝癌細胞に発現するチトクロームP450分子の抗腫瘍免疫誘導における意義 (2009)
  • Author(s): 本間定, 込田英夫, 小井戸薫雄, ほか
  • Organizer: 第45回日本肝臓学会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Presentation] 自己免疫性肝炎マウスモデルにおける制御性T細胞の動態と病態との関連の解析 (2009)
  • Author(s): 佐伯千里、中野真範、及川恒一、高橋宏樹、本間定、ほか
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Presentation] Fusions of human dendritic cells and hepatocellular carcinoma cells induce cytotoxic and regulatory T cells in vitro. (2009)
  • Author(s): Shigeo Koido, Sadamu Homma, Eiichi Hara, et al.
  • Organizer: Keystone Symposia, Dendritic Cells (Z2)
  • Place of Presentation: Banff, Canada.
  • Year and Date: 2009-05-18
• [Presentation] Fusions of human dendritic cells and pancreatic carcinoma cells induce antigen-specific antitumor immune responses. (2009)
  • Author(s): Shigeo Koido, Eiichi Hara, Sadamu Homma, et al.
  • Organizer: Digestive Disease Week
  • Place of Presentation: CHICAGO, ILINOIS
  • Year and Date: 2009-05-15
• [Presentation] 肝血管肉腫に対する抗腫瘍免疫の誘導 (2009)
  • Author(s): 込田英夫, 小井戸薫雄, 本間定, ほか
  • Organizer: 第95回日本消化器病学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-05-09
• [Presentation] 膵臓癌に対する塩酸ゲムシタビンとWT1ペプチドワクチン併用療法の有効性に関する基礎的検討 (2009)
  • Author(s): 高原映崇、本間定、田尻久雄
  • Organizer: 第95回日本消化器病学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-05-08
• [Presentation] トール様受容体を刺激した樹状細胞と熱処理した大腸癌細胞の融合細胞は効果的な細胞傷害性T細胞を誘導する (2009)
  • Author(s): 小井戸薫雄, 込田英夫, 本間定, ほか
  • Organizer: 第95回日本消化器病学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-05-08
• [Presentation] DCワクチンと5-FU併用のNK細胞を介する抗腫瘍増強効果 (2008)
  • Author(s): 永崎栄次郎、高原映崇、小井戸薫雄、相羽恵介、本間定
  • Organizer: 第21回日本バイオセラピィ学会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-18
• [Presentation] 固形腫瘍拒絶抗原としてのHemoglobin-βの効果Short Title : DC-IL12 gene therapy of cancer (2008)
  • Author(s): 込田英夫, 本間定, 小井戸薫雄, ほか
  • Organizer: 第21回日本バイオセラピィ学会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-18
• [Presentation] DCワクチンと5-FU併用のNK細胞を介する抗腫瘍増強効果 (2008)
  • Author(s): Homma S, et al.
  • Organizer: 第21回日本バイオセラピー学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-18
• [Presentation] IL-12遺伝子導入樹状細胞の腫瘍内投与は腫瘍血管を標的とした抗腫瘍抗果を示す (2008)
  • Author(s): 込田英夫、小井戸薫雄、田尻久雄、本間定、ほか
  • Organizer: 第67回 日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-30
• [Presentation] トール様受容体を刺激した樹状細胞と熱処理した癌細胞との融合細胞による細胞傷害性T細胞の誘導 (2008)
  • Author(s): 小井戸薫雄、原栄一、本間定、ほか
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] 初代がん細胞株の樹立 : 大腸がん、膵臓がん、メラノーマ、脳転移性腫瘍 (2008)
  • Author(s): 原栄一、坂本裕彦、小川匡市、渡部道章、田中俊英、本間定、小井戸薫雄
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] 樹状細胞と肝細胞癌との融合細胞ワクチンによる免疫応答の誘導 (2008)
  • Author(s): 小井戸薫雄、本間定、光永真人、ほか
  • Organizer: 第50回日本消化器病学会大会JDDW
  • Place of Presentation: 東京
  • Year and Date: 2008-10-02
• [Presentation] (2008)
  • Author(s): 込田英夫, 小井戸薫雄, 田尻久雄, 本間定, ほか
  • Organizer: 第12回基盤的癌免疫研究会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-02
• [Presentation] 樹状細胞の提示する抗原ペプチドのプロテオーム解析による自己免疫性肝疾患の標的抗原の探索 (2008)
  • Author(s): 本間 定, ほか
  • Organizer: 第44回日本肝臓学会総会
  • Place of Presentation: 松山
  • Year and Date: 2008-06-05
• [Presentation] アロ癌細胞株と自己樹状細胞との融合細胞にて誘導されたMUC1特異的細胞障害性T細胞の特徴 (2008)
  • Author(s): 小井戸薫雄, 本間定, 高原映崇, ほか
  • Organizer: 第94会日本消化器病学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-09