Development of esophageal cancer vaccine therapy using newly identified epitope peptide with TLR-9 agonist

• Project/Area Number: 21791259
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Wakayama Medical University
• Principal Investigator: KATSUDA Masahiro Wakayama Medical University, 医学部, 学内助教 (50464673)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: TLR-9 / CpG-ODN / 癌ワクチン / 食道癌

Research Abstract

In inducing Flu peptide-specific CTLs in vitro, Flu peptide-specific cytotoxicity was enhanced in the presence of each type of CpG-ODN and especially CpG-A and CpG-C showed higher cytotoxic activity than CpG-B on PDC dependent manner. URLC10 peptide specific cytotoxicity was enhanced in the presence of CpG-A on PDC dependent manner. In vitro stimulation with CpG-ODN increased the precursor frequency of peptide-specific CTLs within PBMCs derived from esophageal cancer patients. The supernatant derived from PBMCs stimulated with CpG-ODN (CpG-sup) and IFN-α augmented the cytotoxicity of URLC10 specific CTL clone. These results revealed type-1 IFN induced by CpG-ODNs augmented the cytotoxic activity of the peptide-specific CTLs, cleary revealing one of the mechanism how CpG-ODNs would work as an ideal adjuvant for peptide vaccine therapy against cancer.

Research Products

• [Journal Article] Dendritic cells adenovirally-transduced with full-length mesothelin cDNA elicit mesothelin-specific cytotoxicity against pancreatic cancer cell lines in vitro. (2011)
  • Author(s): Miyazawa M, Iwahashi M, Ojima T, Katsuda M, Nakamura M, Nakamori M, Ueda K, Naka T, Hayata K, Iida T, Yamaue H
  • Journal Title: Cancer Lett. 305(1) Pages: 32-39
  • Peer Reviewed
• [Journal Article] Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer. (2011)
  • Author(s): Iida T, Iwahashi M, Katsuda M, Ishida K, Nakamori M, Nakamura M, Naka T, Ojima T, Ueda K, Hayata K, Nakamura Y, Yamaue H
  • Journal Title: Oncol Rep. 25(5) Pages: 1271-1277
  • Peer Reviewed
• [Journal Article] Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma. (2010)
  • Author(s): Iwahashi M, Katsuda M, Nakamori M, Nakamura M, Naka T, Ojima T, Iida T, Yamaue H
  • Journal Title: Cancer Sci. 101(12) Pages: 2510-2517
  • NAID: 10027834170
  • Peer Reviewed
• [Journal Article] Clinicopathological characteristics of remnant gastric cancer after a distal gastrectomy. (2010)
  • Author(s): Ojima T, Iwahashi M, Nakamori M, Nakamura M, Naka T, Katsuda M, Iida T, Tsuji T, Hayata K, Takifuji K, Yamaue H
  • Journal Title: J Gastrointest Surg. 14(2) Pages: 277-281
  • Peer Reviewed
• [Journal Article] Optimal dose of preoperative enteral immunonutrition for patients with esophageal cancer. (2009)
  • Author(s): Nakamura M, Iwahashi M, Takifuji K, Nakamori M, Naka T, Ishida K, Ojima T, Iida T, Katsuda M, Hayata K, Yamaue H
  • Journal Title: Surg Today. 39(10) Pages: 855-860
  • NAID: 10025555140
  • Peer Reviewed
• [Journal Article] Association of allogeneic blood transfusions and long-term survival of patients with gastric cancer after curative gastrectomy. (2009)
  • Author(s): Ojima T, Iwahashi M, Nakamori M, Nakamura M, Naka T, Katsuda M, Iida T, Hayata K, Yamaue H
  • Journal Title: J Gastrointest Surg. 13(10) Pages: 1821-1830
  • Peer Reviewed
• [Journal Article] Evaluation of double tract reconstruction after total gastrectomy in patients with gastric cancer : prospective randomized controlled trial. (2009)
  • Author(s): Iwahashi M, Nakamori M, Nakamura M, Naka T, Ojima T, Iida T, Katsuda M, Ueda K, Yamaue H
  • Journal Title: World J Surg. 33(9) Pages: 1882-1888
  • Peer Reviewed
• [Journal Article] Influence of overweight on patients with gastric cancer after undergoing curative gastrectomy : an analysis of 689 consecutive cases managed by a single center. (2009)
  • Author(s): Ojima T, Iwahashi M, Nakamori M, Nakamura M, Naka T, Ishida K, Ueda K, Katsuda M, Iida T, Tsuji T, Yamaue H
  • Journal Title: Arch Surg. 144(4) Pages: 351-358
  • Peer Reviewed
• [Journal Article] Comparison of different classes of CpG-ODN in augmenting the generation of human epitope peptide-specific CTLs.
  • Author(s): Katsuda M, Iwahashi M, Matsuda K, Miyazawa M, Nakamori M, Nakamura M, Ojima T, Iida T, Hayata K, Yamaue H
  • Journal Title: Int J Oncol. in press
  • Peer Reviewed
• [Journal Article] Comparison of different classes of CpG-ODN in augmenting the generation of human epitope peptide-specific CTLs.
  • Author(s): Masahiro Katsuda
  • Journal Title: Int J Oncol. Volume: (In press)
  • Peer Reviewed
• [Presentation] Type-I IFNによる癌抗原特異的CTLの細胞障害活性増強効果 (2010)
  • Author(s): 勝田将裕 岩橋誠 中森幹人 中村公紀 尾島敏康 飯田武 辻俊明 早田啓治 松田健司 宮澤基樹 山上裕機
  • Organizer: 第21回日本バイオセラピィー学会学術集会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-10
• [Presentation] Type-1 IFN from PBMCs stimulated by CpG-ODNs auguments proliferation and cytotoxicity of peptide specific CTL clone (2010)
  • Author(s): Masahiro Katsuda, Makoto Iwahashi, Mikihito Nakamori, Masaki Nakamura, Teiji Naka, Toshiyasu Ojima, Takeshi Iida, Toshiaki Tsuji, Keiji Hayata, Kenji Matsuda, Motoki Miyazawa, Hiroki Yamaue
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] 食道癌に対するCpG併用ペプチドワクチン療法第I相臨床試験における免疫学的評価 (2010)
  • Author(s): 勝田将裕、岩橋誠、中森幹人、中村公紀、中禎二、尾島敏康、飯田武、角田卓也、 中村祐輔、山上裕機
  • Organizer: 第64回日本食道学会学術総会
  • Place of Presentation: 久留米
  • Year and Date: 2010-08-31
• [Presentation] TLR-9アゴニスト併用食道癌ペプチドワクチン療法 (2010)
  • Author(s): 勝田将裕、岩橋誠、中森幹人、中村公紀、松田健司、飯田武、宮澤基樹、 角田卓也、中村祐輔、山上裕機
  • Organizer: 第65回日本消化器外科学会総会
  • Place of Presentation: 下関
  • Year and Date: 2010-07-15
• [Presentation] TLR-9 agonistを併用した新規食道癌ペプチドワクチン療法 (2010)
  • Author(s): 勝田将裕 岩橋誠 松田健司 宮澤基樹 中森幹人 中村公紀 尾島敏康 中禎二 飯田武 角田卓也 中村祐輔 山上裕機
  • Organizer: 第31回癌免疫外科研究会
  • Place of Presentation: 大阪
  • Year and Date: 2010-05-20
• [Presentation] CpG-ODNの食道癌ペプチドワクチン療法におけるアジュバント効果-ペプチド特異的CTLクローンを用いた解析- (2010)
  • Author(s): 勝田将裕、岩橋誠、中森幹人、中村公紀、松田健司、中禎二、尾島敏康、飯田武、宮澤基樹、山上裕機
  • Organizer: 第110回日本外科学会
  • Place of Presentation: 名屋
  • Year and Date: 2010-04-08
• [Presentation] CpG-ODNの食道癌ペプチドワクチン療法におけるアジュバント効果-ペプチド特異的CTLクローンを用いた解析- (2010)
  • Author(s): 勝田将裕
  • Organizer: 第110回日本外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-08
• [Presentation] Toll like receptor 9による新規食道癌ペプチド特異的CTLの効率的誘導と細胞障害活性増強効果 (2009)
  • Author(s): 勝田将裕 岩橋誠 中森幹人 中村公紀 中禎二 尾島敏康 飯田武 辻俊明 松田健司 宮澤基樹 山上裕機
  • Organizer: 第37回和歌山悪性腫瘍研究会
  • Place of Presentation: 和歌山
  • Year and Date: 2009-12-10
• [Presentation] CpG-ODNによる癌抗原特異的エフェクター細胞の効率的誘導と抗腫瘍活性増強効果 (2009)
  • Author(s): 勝田将裕、岩橋誠、中森幹人、中村公紀、松田健司、中禎二、尾島敏康、飯田武、宮澤基樹、角田卓也、中村祐輔、山上裕機
  • Organizer: 第21回日本バイオセラピィー学会学術集会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-11-26
• [Presentation] CpG-ODNによる癌抗原特異的エフェクタ-細胞の効率的誘導と抗腫瘍活性増強効果 (2009)
  • Author(s): 勝田将裕
  • 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: 2009-11-26
• [Presentation] TLR-9 agonistを併用した進行食道癌に対する新規エピトープペプチドワクチン療法の第I相臨床試験 (2009)
  • Author(s): 勝田将裕 岩橋誠 中森幹人 中村公紀 松田健司 中禎二 尾島敏康 飯田武 宮澤基樹 角田卓也 中村祐輔 山上裕機
  • Organizer: 第47回日本癌治療学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-23
• [Presentation] CpG-ODNs augment cytotoxic activity of peptide-specific CTLs from patients with esophageal cancer (2009)
  • Author(s): Masahiro Katsuda, Makoto Iwahashi, Mikihito Nakamori, Masaki Nakamura, Kenji Matsuda, Teiji Naka, Toshiyasu Ojima, Takeshi Iida, Motoki Miyazawa, Hiroki Yamaue
  • 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] 進行食道癌に対するCpG-B併用URLC10およびTTKエピトープペプチドワクチン療法の第I相臨床試験 (2009)
  • Author(s): 勝田将裕 岩橋誠 松田健司 宮澤基樹 中森幹人 中村公紀 中禎二 尾島敏康 飯田武 山上裕機
  • Organizer: 第64回日本消化器外科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-17
• [Presentation] 標準療法不応進行食道癌に対するCpG-B併用癌抗原ペプチドワクチン療法の第I相臨床試験 (2009)
  • Author(s): 勝田将裕 岩橋誠 松田健司 宮澤基樹 飯田武 中森幹人 中村公紀 角田卓也 中村祐輔 山上裕機
  • Organizer: 第63回日本食道学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-06-26
• [Presentation] 食道癌ペプチドワクチンの抗原特異的CTL誘導におけるCpG-ODNのアジュバント効果に関する基礎的検討 (2009)
  • Author(s): 勝田将裕
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-04-03