Development of an immune therapy against advanced solid tumors using the epitope peptides derived from novel tumor-associated antigens

• Project/Area Number: 20790498
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Kyushu University
• Principal Investigator: MUTSUNORI Iga Kyushu University, 大学病院, 助教 (20422420)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 胆道学 / 膵臓学 / 腫瘍免疫 / 腫瘍抗原ペプチドワクチン / 制御性T細胞 / 臨床試験 / シクロフォスファミド / CD8+T細胞 / IFNγ産生 / ELISPOTアッセイ

Research Abstract

This is an open-label, Phase I dose-escalation study targeting HLA-A^*2402- positive patients with advanced, metastatic, and/or recurrent gastrointestinal cancer, cholangiocellular carcinoma, pancreatic cancer, small cell and non-small cell lung cancer, and cervical cancer. The study treatments include pre-administration of cyclophosphamide (CPM) to exclude regulatory T cells, vaccination with five HLA-A^*2402 restricted peptides derived from tumor-associated antigens, followed by administration of low-dose IL-2. The primary endpoint of safety was investigated in a CPM dose-escalation study that included a cohort of three patients. The secondary endpoint was to observe the induction of antigen-specific immune responses and clinical antitumor response. Twenty-two patients satisfying the eligibility criteria enrolled in this study, and the vaccination protocol was found to be well tolerated in 17 enrolled patients. Stable disease (SD) was observed in 8 of 15 patients. Immunological analysis will be demonstrated in these patients.

Research Products

• [Journal Article] Non-transmissible Sendai virus encoding granulocyte macrophage colony-stimulating factor is a novel and potent vector system for producing autol ogous tumor vaccines (2008)
  • Author(s): Inoue, H., Iga, M., Tani, K., et.al.
  • Journal Title: Cancer Sci 99 Pages: 2315-2326
  • Peer Reviewed
• [Journal Article] TARC and RANTES enhance antitumor immunity induced by the GM-CSF-transduced tumor vaccine in a mouse tumor model (2008)
  • Author(s): Inoue, H., Iga, M., Tani, K., et.al.
  • Journal Title: Cancer Immunol Immun 57 Pages: 1399-1411
  • Peer Reviewed
• [Presentation] New strategies of immune and cell therapy targeting malignancy (2009)
  • Author(s): 伊賀睦了
  • Organizer: 第71回日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-23
• [Presentation] 進行・再発固形腫瘍に対するシクロフォスファミド併用新規腫瘍関連抗原由来ペプチドを用いた腫瘍特異的強化ワクチン療法 (2009)
  • Author(s): 土方康基
  • Organizer: 第106回日本内科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-04-10
• [Presentation] New strategies of immune and cell therapy targeting malignancy. (2009)
  • Author(s): Iga M, Hijikata Y, Suehiro Y, Inoue H, Tanaka Y, Shimoda S, Marumoto T, Okazaki T, Tsunoda T, Nakamura Y, Tani K
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] 進行再発固形腫瘍に対するシクロフォスファミド併用新規腫瘍関連抗原由来ペプチドを用いた腫瘍特異的強化ワクチン療法 (2009)
  • Author(s): 伊賀睦了、土方康基、末廣陽子、岡崎利彦、村上佑介、田中芳浩、中村祐輔、吉田浩二、角田卓也、谷憲三朗
  • Organizer: 第106回日本内科学会総会
  • Place of Presentation: 東京
• [Presentation] 進行・再発固形腫瘍 (消化器がん・肺がん・子宮頚がん) に対するシクロフォスファミド併用新規腫瘍関連抗原由来エピトープペプチドカクテルを用いた腫瘍特異的強化ワクチン療法第1相臨床試験 (2008)
  • Author(s): 伊賀睦了
  • Organizer: 第21回日本バイオセラピィ学会学術集会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-29
• [Presentation] 進行再発固形腫瘍に対する抗腫瘍ワクチン療法第1相臨床試験 (2008)
  • Author(s): 谷憲三朗、伊賀睦了、土方康基、末廣陽子、岡崎利彦、村上佑介、田中芳浩、中村祐輔、吉田浩二、角田卓也
  • Organizer: 第21回日本日本バイオセラピィ学会学術集会総会
  • Place of Presentation: 東京