Development of cancer immunotherapy targeting mutation-derived neoantigens
| Project/Area Number |
16K07162
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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 |
Tumor therapeutics
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| Research Institution | Aichi Cancer Center Research Institute (2018)
The University of Tokyo (2016-2017) |
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Principal Investigator |
MATSUSHITA Hirokazu 愛知県がんセンター(研究所), 腫瘍免疫制御TR分野, 分野長 (80597782)
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| Co-Investigator(Kenkyū-buntansha) |
久米 春喜 東京大学, 医学部附属病院, 教授 (10272577)
中川 徹 帝京大学, 医学部, 教授 (40591730)
垣見 和宏 東京大学, 医学部附属病院, 特任教授 (80273358)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 腎癌 / 遺伝子変異 / ネオ抗原 / MHC結合予測アルゴリズム / 腎がん / ネオエピトープ / MHC class I 結合予測 / T細胞 / HLA-A2 / トランスジェニックマウス / IFN-gamma / HLA-A2 トランスジェニックマウス / MHCクラスI結合予測 / HLA-A2トランスジェニックマウス / IFNg |
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| Outline of Final Research Achievements |
For the purpose of developing immunotherapy of renal cell carcinoma (RCC) targeting neo-antigens derived from somatic mutations, using in silico MHC binding prediction algorithm for the data of the exome/RNA sequencing of 5 RCC cases, 121 HLA-A2 restricted candidate neo-epitopes have been identified. The immune response to these neo-epitope peptides first was screened using HLA-A2 transgenic mice, strong reaction was detected in 15 peptides. Then, we examined the immune responses of human peripheral blood mononuclear cells (PBMCs) from HLA-A2 positive healthy donor for the 15 peptides. The reaction was observed for a neo-epitope derived from PTEN gene mutation.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトの腎がん組織からエクソーム/RNAシーケンスにより体細胞変異を同定し、MHC結合予測アルゴリズムを用いて候補ネオエピトープを同定した。そして、実際に合成したネオエピトープペプチドに対するヒト正常人PBMCの免疫反応を、人工抗原提示細胞等を利用した我々のアッセイシステムで検出可能であった。本研究を通じて、非常に頻度の低いヒト末梢血中のネオエピトープ特異的T細胞を検出することが可能な培養法とアッセイ法を確立することができ、今後、他のがんのネオエピトープの同定にも応用できる可能性が示された。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Increased diversity with reduced "diversity evenness" of tumor infiltrating T-cells for the successful cancer immunotherapy.2018
Author(s)
Hosoi A, Takeda K, Nagaoka K, Iino T, Matsushita H, Ueha S, Aoki S, Matsushima K, Kubo M, Morikawa T, Kitaura K, Suzuki R, Kakimi K.
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Journal Title
Sci Rep
Volume: 8
Issue: 1
Pages: 1058-1058
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The frequency of neoantigens per somatic mutation rather than overall mutational load or number of predicted neoantigens per se is a prognostic factor in ovarian clear cell carcinoma.2017
Author(s)
Matsushita H, Hasegawa K, Oda K, Yamamoto S, Nishijima A, Imai Y, Asada K, Ikeda Y, Karasaki T, Fujiwara K, Aburatani H, Kakimi K.
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Journal Title
Oncoimmunology
Volume: 6
Issue: 8
Pages: e1338996-e1338996
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Prediction and prioritization of neoantigens: integration of RNA sequencing data with whole-exome sequencing.2017
Author(s)
Karasaki T, Nagayama K, Kuwano H, Nitadori JI, Sato M, Anraku M, Hosoi A, Matsushita H, Takazawa M, Ohara O, Nakajima J, Kakimi K.
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Journal Title
Cancer Sci.
Volume: 108(2)
Issue: 2
Pages: 170-177
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Neoantigen load and HLA-class I expression characterize a subset of HR-proficient high-grade serous ovarian carcinomas with favorable prognosis and T cell-inflamed phenotype.2018
Author(s)
Hirokazu Matsushita, Kosei Hasegawa, Katsutoshi oda, Shogo Yamamoto, Kayo Asada, Akira Yabuno, Akira Nishijima, Takahiro krasaki, Yuji Ikeda, Keiichi Fujiwara, Hiroyuki Aburatani, Kazuhito Kakimi
Organizer
AACR(American Association for Cancer Research) Annual Meeting 2018
Related Report
Int'l Joint Research
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[Presentation] Neoantigen frequency as an independent prognostic factor in patients with clear ovarian carcinoma(CCOC)2017
Author(s)
Hirokazu Matsushita, Kosei Hasegawa, Katsutoshi Oda, Shogo Yamamoto, Akira Nishijima, Yuichi Imai, Kayo Asada, Yuji Ikeda, Takahiro Karasaki, Keiichi Fujiwara, Hiroyuki Aburatani, Kazuhiro Kakimi
Organizer
AACR(American Association for Cancer Research) Annual Meeting 2017
Related Report
Int'l Joint Research
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