Development of cancer immunotherapy using tumor-associated antigen-derived long peptides and liberation from immune suppression mediated trough IL-6 signaling
| Project/Area Number |
15H04311
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Kumamoto University |
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Principal Investigator |
Nishimura Yasuharu 熊本大学, 生命資源研究・支援センター, シニア教授 (10156119)
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| Co-Investigator(Kenkyū-buntansha) |
入江 厚 熊本大学, 大学院生命科学研究部(医), 講師 (30250343)
河野 健司 大阪府立大学, 工学(系)研究科(研究院), 教授 (90215187)
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| Co-Investigator(Renkei-kenkyūsha) |
Eto Masatoshi 九州大学, 大学院医学研究院, 教授 (90315078)
Nakayama Hideki 熊本大学, 大学院生命科学研究部, 教授 (70381001)
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| Research Collaborator |
Tsukamoto Hirotake (Awai Hirotake) 熊本大学, 大学院生命科学研究部, 講師 (10433020)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2015: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | 腫瘍免疫 / 腫瘍関連抗原 / 抗原ペプチド / 細胞傷害性T細胞 / ヘルパーT細胞 / IL-6シグナル / 免疫抑制的腫瘍微小環境 / 免疫抑制解除 / がん免疫療法 / 腫瘍関連抗原ペプチド / 細胞傷害性Ｔ細胞 / 免疫抑制 / IL-6 シグナル / ＨＬＡ / がん抗原ワクチン / 長鎖がん抗原ペプチド / 免疫抑制解除療法 / 癌抗原 / 癌抗原ワクチン / 長鎖癌抗原ペプチド |
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| Outline of Final Research Achievements |
We previously identified novel tumor-associated antigens (TAAs) frequently overexpressed in various cancers. In this study we identified these TAAs-derived long peptides (LPs) that can induce both Th1 cells restricted by common HLA class II molecules, and tumor-reactive CTLs specific to SPs included in LPs by cross-presentation in both human in vitro culture and HLA-transgenic mice in vivo. These LPs were naturally presented by DC and these TAA-LPs-specific Th cells were observed in cancer patients suggesting usefulness of these peptides for cancer immunotherapy. We demonstrated that tumor-specific Th1 cells was attenuated in tumor-bearing mice and cancer patients in an IL-6 and soluble IL-6 receptor (sIL-6R)-dependent manner. Abundant IL-6/sIL-6R was produced by myeloid cells in tumor-bearing mice and inhibition of IL-6-mediated signals restored the T cell-mediated tumor immunity suggesting that IL-6/sIL-6R is a rational target to augment T-cell-mediated cancer immunotherapy.
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Report
(4 results)
Research Products
(53 results)
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[Journal Article] Soluble IL-6R expressed by myeloid cells reduces tumor-specific Th1 differentation and drives tumor progression2017
Author(s)
Tsukamoto H, Fujieda K, Hirayama M, Ikeda T, Yuno A, Matsumura K, Fukuma D, Araki K, Mizuta H, Nakayama H, Senju S, Nishimura Y
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Journal Title
Cancer Research
Volume: 14
Issue: 9
Pages: 2279-2291
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] An oncofetal antigen, IMP-3-derived long peptides induce immune responses of both helper T cells and CTLs2016
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
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Journal Title
OncoImmunology
Volume: 5
Issue: 6
Pages: e1123368-e1123368
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Generation of Large Numbers of Antigen-Expressing Human Dendritic Cells Using CD14-ML Technology2016
Author(s)
Yuya Imamura, Miwa Haruta, Yusuke Tomita, Keiko Matsumura, Tokunori Ikeda, Akira Yuno1, Masatoshi Hirayama, Hideki Nakayama, Hiroshi Mizuta, Yasuharu Nishimura, Satoru Senju
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Journal Title
Plos One
Volume: 11
Issue: 4
Pages: e0152384-e0152384
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Identification of glypican-3-derived long peptides activating both CD8 and CD4 T cells; prolonged overall survival in cancer patients with Th cell response2016
Author(s)
Sayem, M. A. Tomita, Y. Yuno, A. Hirayama, M. Irie, A. Tsukamoto, H. Senju, S. Yuba, E. Yoshikawa, T. Kono, K. Nakatsura, T. Nishimura, Y.
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Journal Title
Oncoimmunology
Volume: 5
Issue: 1
Pages: e1062209-e1062209
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Identification of bladder cancer-associated cancer-testis antigens-derived long peptides encompassing both CTL and promiscuous HLA class II-restricted Th cell epitopes2018
Author(s)
Nishimura Y, Tsuruta M, Ueda S, Poh Yin Yew PY, Fukuda I, Yoshimura S, Kishi H, Hamana H, Hirayama M, Yatsuda J, Irie A, Senju S, Yuba E, Kamba T, Eto M, Nakayama H
Organizer
The American Association for Cancer Research (AACR) Annual Meeting 2018
Related Report
Int'l Joint Research
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[Presentation] Is there a revival of the cancer vaccine?2016
Author(s)
Yasuharu Nishimura
Organizer
Educational Session: What you should know about cancer immunotherapy, The European Society of Medical Oncology (ESMO) Asia
Place of Presentation
Suntec Singapore Convention & Exhibition Centre （シンガポール）
Year and Date
2016-12-16
Related Report
Int'l Joint Research / Invited
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[Presentation] Next generation combined cancer vaccines.2016
Author(s)
Yasuharu Nishimura, Masatoshi Hirayama, Mohammad Abu Sayem, Yuya Imamura, Satoru Senju, Akira Yuno, Yusuke Tomita, Yoshihiro Yoshitake, Kenji Kawano, Tetsuya Nakatsura, Yusuke Nakamura, Masanori Shinohara and Hideki Nakayama.
Organizer
The Core Symposia 2 "Beyond the immune checkpoint blockade", The 75th Annual Meeting of Japanese Association of Cancer.
Place of Presentation
Pacifico Yokohama （神奈川県 横浜市）
Year and Date
2016-10-06
Related Report
Invited
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[Presentation] Identification of oncofetal antigen (IMP-3)-derived long peptides encompassing both CTL epitopes and multiple HLA class II-restricted Th cell epitopes2015
Author(s)
Hirayama, M., Tomita, Y., Yuno, A., Sayem M.A., Nakane, M., Tsukamoto, H., Irie, A., Senju, S., Yoshitake, Y., Fukuma, D., Shinohara, M., Yuba, E., Kono, K., Yoshida, K., Nakamura, Y., Nakayama, H., Nishimura, Y.
Organizer
International Conference of Cancer Immunotherapy and Macrophages 2015
Place of Presentation
Ito Hall, Ito International Research Center, The University of Tokyo, Tokyo
Year and Date
2015-07-09
Related Report
Int'l Joint Research
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[Presentation] Identification of oncofetal antigen Glypican-3-derived long peptides encompassing CTL and multiple HLA class II-restricted Th cell epitopes2015
Author(s)
Sayem M.A., Tomita, Y., Yuno, A., Hirayama, M., Yuba, E., Kono, K., Yoshikawa, T., Nakatsura, T., Nishimura, Y.
Organizer
13th CIMT (Cancer Immunotherapy) Annual Meeting
Place of Presentation
Rheingold Halle Congress Center, Germany
Year and Date
2015-05-11
Related Report
Int'l Joint Research
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