Development of a novel cancer immunotherapy using the artificial proteins consisted in the functional peptide motifs.

• Project/Area Number: 22650231
• 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: ITO Masaki 東京慈恵会医科大学, 医学部, 助教 (80297366)
• Co-Investigator(Kenkyū-buntansha): HOMMA Sadamu 東京慈恵会医科大学, 医学部, 准教授 (50192323) ; KOIDO Shigeo 東京慈恵会医科大学, 医学部, 准教授 (70266617)
• Co-Investigator(Renkei-kenkyūsha): SHIBA Kiyotaka がん研究所, 蛋白創製研究部, 部長 (40196415)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,190,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 人工タンパク質 / MolCraft / 細胞性免疫 / OVA / 樹状細胞 / 腫瘍免疫 / 液性免疫 / がん / 腫瘍免疫療法 / 人工蛋白質 / 免疫 / WT1

Research Abstract

We have constructed an artificial protein library by combinatorially assembling four peptide motifs associated with the MHC class I epitope and MHC class II epitope of OVA(Ovalbumin), alpha-helical motif and randomized peptide sequence, respectively. We have generated two artificial proteins, F37A and F182A, which have the ability to induce OVA-specific cellular immunity without using any adjuvant. These exogenous proteins presented OVA-specific MHC class I epitope through the cross-presentation pathway in the antigen presenting cells. Our studies have demonstrated that the motif-programmed artificial proteins might be able to induce cellular immunity contribute to cancer immunotherapy.

Research Products

• [Journal Article] Gemcitabine enhances Wilms' tumor gene Immunotherapy synergizes with chemotherapy targeting pancreatic cancer (2012)
  • Author(s): Koido S., Homma S., Ito M., et al.
  • Journal Title: Immunotherpy Volume: 4 Issue: 1 Pages: 5-7
  • DOI: 10.2217/imt.11.150
  • Peer Reviewed
• [Journal Article] Current immunotherapeutic approaches in pancreatic cancer (2011)
  • Author(s): Koido S., Homma S., Ito M., et al.
  • Journal Title: Clin Dev Immunol Volume: 267539 Pages: 1-15
  • DOI: 10.1155/2011/267539
  • Peer Reviewed
• [Journal Article] Immunologic monitoring of cellular responses by Dendritic/Tumor cell fusion vaccines (2011)
  • Author(s): Koido S., Homma S., Ito M., et al.
  • Journal Title: Journal of Biomedicine and Biotechnology Volume: 910836 Issue: 1 Pages: 1-14
  • DOI: 10.1155/2011/910836
  • 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, et al
  • Journal Title: Cancer Immunol Immunother Volume: 60(9) Issue: 9 Pages: 1289-97
  • DOI: 10.1007/s00262-011-1033-3
  • 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: Biochemical and Biophysical Research Communications Volume: 400 Issue: 3 Pages: 548-553
  • DOI: 10.1016/j.bbrc.2010.06.096
  • 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, Tajiri H
  • Journal Title: Clin Dev Immnol Volume: 51678
  • Peer Reviewed
• [Journal Article] Dendritic/pancreatic carcinoma fusions for clinical use : Comparative functional analysis of helthy-versus patient-derived fusions (2010)
  • Author(s): Koido S, Hara E, Homma S, Namiki Y, Komita H
  • Journal Title: Clin Immunol. Volume: 135(3) Pages: 384-400
  • Peer Reviewed
• [Journal Article] Accumulation of functional regulatory T cells in actively inflamed liver in mouse dendritic cell-based autoimmune hepatic inflammation (2010)
  • Author(s): Saeki C, Homma S, et al.
  • Journal Title: Clin Immunol. Volume: 135 Pages: 156-166
  • Peer Reviewed
• [Journal Article] A heat shock protein 70-based vaccine with enhanced immunogenicity for clinical use (2010)
  • Author(s): Gong J, Koido S, et al.
  • Journal Title: J Immunol. Volume: 184 Pages: 488-496
  • Peer Reviewed
• [Journal Article] Combined treatment with dendritic cells and 5-fluorouracil elicits augmented NK cell-mediated antitumor activity through the 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(5) Pages: 467-74
  • Peer Reviewed
• [Presentation] Study of photodynamic diagnosis of colon cancer generated in DSS(Dextran sulfate sodium) utilizing Apc(Adenomatous polyposis Coli) knockout mice by visualization following oral 5-aminolevulinic acid sensitization (2012)
  • Author(s): Komoike A, Homma S, Ito M, et al
  • Organizer: DDW Digestive Disease Weeks
  • Place of Presentation: San Diego, CA USA
  • Year and Date: 2012-05-20
• [Presentation] iPS細胞から腫瘍血管を標的とした癌ワクチンの開発 (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70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [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] 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
• [Remarks]
  • URL: http://www.jikei.ac.jp/academic/course/17_akuseisyuyo.html
• [Remarks]
  • URL: http://www.jikei.ac.jp/academic/course/17_akuseisyuyo.html