Development of cell preparations and high/low molecular-weight therapeutics that exhibit synergistic effects with PD-1 immune checkpoint antibodies
| Project/Area Number |
16K08844
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Nagasaki University |
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Principal Investigator |
TANAKA Yoshimasa 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (90280700)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | PD-1 / 免疫チェックポイント阻害剤 / QOL / 奏効率 / 細胞製剤 / ビスホスホン酸 / スクリーニグ / 創薬ライブラリー / PD-L1 / 免疫チェックポイント / シグナル / BcL-XL / ミトコンドリア / 抗腫瘍作用 / 肺がん / 成人T細胞白血病 / 乳がん / がん免疫療法 / IL-18 / γδ型T細胞 / 癌 / 免疫学 / 蛋白質 / 有機化学 / バイオテクノロジー |
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| Outline of Final Research Achievements |
PD-1 immune checkpoint inhibitors are expected to maintain a high level of QOL, compared to the current standard therapies, whereas the efficacy is only 10%~30%. In this study, we explored cell preparations and high/low molecular-weight therapeutics that had synergistic effects when combined with the antibodies. Regarding cell preparations, we selected gammadelta T cells and established an efficient expansion protocol for expansion of the cells, in which the fourth-generation bisphosphonate was used. When it comes to high molecular-weight therapeutics, we used an E. coli expression system and examined the synergistic effect of the proteinaceous preparations with PD-1 immune checkpoint inhibitors. As for low molecular-weight therapeutics, we screened a Nagasaki University chemical library and obtained several hit compounds.
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| Academic Significance and Societal Importance of the Research Achievements |
PD-1免疫チェックポイント阻害剤を用いたがん免疫治療研究は1999年頃から開始され、実際に動物実験で抗PD-L1抗体の抗腫瘍効果が確認されたのは2001年頃であった。この時から、奏功率の低さが問題となっていたが、奏功率の改善は困難であった。本研究課題においてはPD-1免疫チェックポイント阻害剤との併用剤を、低分子、高分子、細胞製剤の中に見出すことができた。今後、これらの製剤に関して臨床試験を行い、その併用効果が確認できれば、これまでの適用症例に関してより高い奏効率が期待できるだけでなく、適応症例とならなかった他のがん種についても新たな適用を取得できる可能性がある。
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Report
(4 results)
Research Products
(38 results)
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[Journal Article] Identification and structure of an MHC class I-encoded protein with the potential to present N-myristoylated 4-mer peptides to T cells2019
Author(s)
Yukie Yamamoto, Daisuke Morita, Yoko Shima, Akihiro Midorikawa, Tatsuaki Mizutani, Juri Suzuki, Naoki Mori, Takashi Shiina, Hidetoshi Inoko, Yoshimasa Tanaka, Bunzo Mikami and Masahiko Sugita
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Journal Title
Journal of Immunology
Volume: In press
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effect of IL-18 on the Expansion and Phenotype of Human Natural Killer Cells: Application to Cancer Immunotherapy2018
Author(s)
Hiroaki Senju, Asuka Kumagai, Yoichi Nakamura, Hiroyuki Yamaguchi, Katsumi Nakatomi, Shota Fukami, Kengo Shiraishi, Yuka Harada, Mitsuhiro Nakamura, Haruki Okamura, Yoshimasa Tanaka and Hiroshi Mukae
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Journal Title
International Journal of Biological Sciences
Volume: 14
Pages: 331-340
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Anti-Tumor Activity and Immunotherapeutic Potential of a Bisphosphonate Prodrug2017
Author(s)
Tanaka, Y.; Iwasaki, M.; Murata-Hirai, K.; Matsumoto, K.; Hayashi, K.; Okamura, H.; Sugie, T.; Minato, N.; Morita, C. T.; Toi, M.
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Journal Title
Scientific Reports
Volume: 7
Pages: 5987-5987
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Targeting Lymphoma and Myeloid Leukemia Cells with Bisphosphonate Prodrugs.2016
Author(s)
Matsumoto, K, Hayashi, K, Murata-Hirai, K., Iwasaki, M., Okamura, H., Minato, N., Morita, CT., and Tanaka, Y.
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Journal Title
ChemMedChem
Volume: 11
Pages: 2656-2663
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Immuno-modulatory effects of zoledronic acid on gammadelta T cells in postmenopausal women undergoing neoadjuvant endocrine therapy for early-stage breast cancer2018
Author(s)
Tomoharu Sugie, Eiji Suzuki, Akira Yamauchi, Kazuhiko Yamagami, Norikazu Masuda, Naomi Gondo, Eriko Sumi, Takafumi Ikeda, Harue Tada, Ryuji Uozumi, Shotaro Kanao, Yoshimasa Tanaka, Yoko Hamazaki, Nagahiro Minato, Masakazu Toi
Organizer
The 45th Naito Conference: Immunological and Molecular Bases for Cancer Immunotherapy
Related Report
Int'l Joint Research
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[Presentation] KID-001, a novel TDO/IDO inhibitor, suppresses the AHR-TIPARP pathway to reduce HBV replication in human hepatocytes2018
Author(s)
Seiichi Sato, Taisho Yamada, Kenji Matsuno, Kai Li, Koichi Watashi, Takaji Wakita, Yoshimasa Tanaka, Yasuhito Tanaka, and Akinori Takaoka
Organizer
6th Japan-Taiwan-Korea HBV Research Symposium 2018
Related Report
Int'l Joint Research
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[Presentation] Immuno-modulatory effects of zoledronic acid on gamma delta T cells in postmenopausal women undergoing neoadjuvant endocrine therapy for early-stage breast cancer2018
Author(s)
Tomoharu Sugie, Eiji Suzuki, Akira Yamauchi, Kazuhiko Yamagami, Norikazu Masuda, Naomi Gondo, Eriko Sumi, Takafumi Ikeda, Harue Tada, Ryuji Uozumi, Shotaro Kanao, Yoshimasa Tanaka, Yoko Hamazaki, Nagahiro Minato, Masakazu Toi
Organizer
The 45th Naito Conference: Immunological and Molecular Bases for Cancer Immunotherapy
Related Report
Int'l Joint Research
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