Development of peptide-based cancer immunotherapy using tumor antigen-derived long peptides for oral cancer patients

• Project/Area Number: 16H07082
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University
• Principal Investigator: Hirayama Masatoshi 熊本大学, 医学部附属病院, 診療助手 (50779171)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 口腔がん / がん免疫療法 / 口腔癌 / 腫瘍免疫 / がんペプチドワクチン療法 / がんペプチワクチン療法 / 腫瘍関連抗原

Outline of Final Research Achievements

In this study, to develop more effective cancer immunotherapy for oral cancer patients, we attempted to identify several HLA class II-restricted long peptides derived from some tumor antigens. We also tried to develop the biomarkers to predict the therapeutic effects of peptide-based cancer immunotherapy for oral cancer patients.
As a result, we identified several long peptides derived from cancer antigens, such as IMP-3, DEPDC1, and MPHOSPH1. Some of these peptide could activate both helper T cells and cytotoxic T cells, suggesting that these peptides are useful for exhibiting stronger anti-tumor immune responses. In addition, we identified T cells receptors of these tumor antigen-specific helper T cells.

Research Products

• [Journal Article] Bladder cancer-associated cancer-testis antigen-derived long peptides encompassing both CTL and promiscuous HLA class II-restricted Th cell epitopes induced CD4+ T cells expressing converged T-cell receptor genes in vitro (2018)
  • Author(s): Tsuruta Miki、Ueda Shohei、Yew Poh Yin、Fukuda Isao、Yoshimura Sachiko、Kishi Hiroyuki、Hamana Hiroshi、Hirayama Masatoshi、Yatsuda Junji、Irie Atsushi、Senju Satoru、Yuba Eiji、Kamba Tomomi、Eto Masatoshi、Nakayama Hideki、Nishimura Yasuharu
  • Journal Title: OncoImmunology Volume: 7 Issue: 4 Pages: 1415687-1415687
  • DOI: 10.1080/2162402x.2017.1415687
  • Peer Reviewed / Open Access
• [Journal Article] Predictive value of the combination of SMAD4 expression and lymphocyte infiltration in malignant transformation of oral leukoplakia. (2017)
  • Author(s): Sakata J, Yoshida R, Matsuoka Y, Nagata M, Hirosue A, Kawahara K, Nakamura T, Nakamoto M, Hirayama M, Takahashi N, Nakashima H, Arita H, Ogi H, Hiraki A, Shinohara M, Nakayama H
  • Journal Title: Cancer medicine Volume: 6 Issue: 4 Pages: 730-738
  • DOI: 10.1002/cam4.1005
  • Peer Reviewed / Open Access
• [Journal Article] Myeloid cell-derived soluble IL-6 receptor diminishes the differentiation of tumor-specific Th1 cells to exacerbate tumor progression (2017)
  • Author(s): Tsukamoto H., Fujieda K., Hirayama M., Yuno A., Ikeda T., Matsumura K., Fukuma D., Araki K., Mizuta H., Nakayama H., Senju S., Nishimura Y.
  • Journal Title: Cancer Research Volume: 77 Pages: 2279-2291
  • Peer Reviewed
• [Journal Article] An oncofetal antigen, IMP-3-derived long peptides induce immune responses of both helper T cells and CTLs (2016)
  • Author(s): M. Hirayama, Y. Tomita, A. Yuno, H. Tsukamoto, S. Sejju, Y. Imamura, M. A. Sayem, A. Irie, Y. Yoshitake, D. Fukuma, M. Shinohara, A. Hamada, H. Jono, E. Yuba, K. Kono, K. Yoshida, T. Tsunoda, H. Nakayama, Y. Nishimura
  • Journal Title: OncoImmunology Volume: 5 Issue: 6 Pages: e1123368-e1123368
  • DOI: 10.1080/2162402x.2015.1123368
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The present status and future prospects of peptide-based cancer vaccines. (2016)
  • Author(s): Hirayama M, Nishimura Y
  • Journal Title: Int Immunol Volume: 28 Issue: 7 Pages: 319-328
  • DOI: 10.1093/intimm/dxw027
  • Peer Reviewed / Open Access
• [Journal Article] Generation of Large Numbers of Antigen-Expressing Human Dendritic Cells Using CD14-ML Technology (2016)
  • Author(s): Yuya Imamura, Miwa Haruta, Yusuke Tomita, Keiko Matsumura, Tokunori Ikeda, Akira Yuno1, Masatoshi Hirayama, Hideki Nakayama, Hiroshi Mizuta, Yasuharu Nishimura, Satoru Senju
  • Journal Title: Plos One Volume: 11 Issue: 4 Pages: e0152384-e0152384
  • DOI: 10.1371/journal.pone.0152384
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 口腔癌患者に対する放射線外照射治療における金属補綴物除去の有効性の検討 (2018)
  • Author(s): 井上 和繁、平山 真敏、吉田 遼司、廣末 晃之、川原 健太、高橋 望、有田 英生、中山 秀樹
  • Organizer: 第36回日本口腔腫瘍学会学術大会
• [Presentation] 口腔癌術後患者に対する Adjuvant ペプチドワクチン療法の臨床試験に関する検討 (2017)
  • Author(s): 平山真敏、福間大喜、 湯野晃、中根未季、小島拓、吉武義泰、尾木秀直、廣末晃之、吉田遼司、田中拓也、川原健太、篠原正徳、城野博史、西村泰治、中山秀樹
  • Organizer: 第55回日本癌治療学会学術集会
• [Presentation] 膀胱癌関連がん精巣抗原由来の長鎖ペプチドに特異的な HLA 拘束性 T 細胞の免疫応答と TCR の解析 (2017)
  • Author(s): 鶴田未季、上田翔平、平山真敏、矢津田旬二、入江厚 、千住覚 、 神波大己 、江藤正俊、中山秀樹、西村泰治
  • Organizer: 第26回日本組織適合性学会大会
• [Presentation] 口腔癌での化学放射線治療におけるスぺーサー、および補綴物除去の有効性の検討 (2017)
  • Author(s): 井上 和繁、平山 真敏、吉田 遼司、廣末 晃之、川原 健太、高橋 望、有田 英生、中山 秀樹
  • Organizer: 第55回日本癌治療学会学術集会
• [Presentation] 2種類の膀胱癌関連がん精巣抗原に由来する長鎖ペプチドにより誘導されるCTL/TH1細胞とTCRの解析 (2017)
  • Author(s): 鶴田 未季、上田 翔平、平山 真敏、矢津田 旬二、入江 厚、千住 覚、江藤 正俊、中山 秀樹、西村 泰治
  • Organizer: 第21回日本がん免疫学会総会
• [Presentation] 右側下顎歯肉に生じた分類不能肉腫の1例 (2017)
  • Author(s): 大山徹、平山真敏、廣末晃之、吉田遼司、永田将士、川原健太、尾木秀直、田中拓也、福間大喜、三上芳喜、中山秀樹
  • Organizer: 第36回日本口腔腫瘍学会学術大会
• [Presentation] Identification of cancer-testis antigen (DEPDC1 and MPHOSPH1)-derived long peptides encompassing both CTL and HLA class II-restricted Th cell epitopes. (2016)
  • Author(s): NAKANE Miki, HIRAYAMA Masatoshi, UEDA Shohei, SAYEM Mohammad Abu, YATSUDA Junji, IRIE Atsushi, SENJU Satoru, ETO Masatoshi, NAKAYAMA Hideki and NISHIMURA Yasuharu
  • Organizer: 第45回 日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター、沖縄
  • Year and Date: 2016-12-05
• [Presentation] 腫瘍関連抗原IMP-3由来のCTLとTh細胞の誘導活性を併せ持つ長鎖ペプチドの同定 (2016)
  • Author(s): 平山真敏、湯野晃、中根未季、小島拓、福間大喜、中山秀樹
  • Organizer: 第61回 日本口腔外科学会総会・学術大会
  • Place of Presentation: 幕張メッセ、千葉
  • Year and Date: 2016-11-25
• [Book] 遺伝子医学MOOK 31号（CTLとTh細胞を共に活性化できるがんペプチドワクチン療法の開発） (2017)
  • Author(s): 平山真敏、西村泰治
  • Total Pages: 6
  • Publisher: 洋土社
• [Book] がん抗原ワクチン療法の現状と展望 (2016)
  • Author(s): 平山真敏、西村泰治
  • Total Pages: 8
  • Publisher: 羊土社 実験医学