Neoantigen analysis in tumor tissues for development of personalized precision cancer immunotherapy
Project/Area Number |
18K08577
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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Research Institution | Kyushu University |
Principal Investigator |
KUBO Makoto 九州大学, 医学研究院, 准教授 (60403961)
|
Co-Investigator(Kenkyū-buntansha) |
甲斐 昌也 九州大学, 大学病院, 助教 (10755242)
大内田 研宙 九州大学, 大学病院, 講師 (20452708)
中村 雅史 九州大学, 医学研究院, 教授 (30372741)
大西 秀哉 九州大学, 医学研究院, 准教授 (30553276)
水元 一博 九州大学, 大学病院, 准教授 (90253418)
森崎 隆 九州大学, 医学研究院, 共同研究員 (90291517)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | ネオアンチゲン / がん微小環境 / 腫瘍免疫 / 乳癌 / 腫瘍遺伝子変異量 / 腫瘍浸潤リンパ球 / がんゲノム / 免疫チェックポイント阻害薬 / Tumor mutational burden / ペプチドがんワクチン療法 |
Outline of Final Research Achievements |
Analysis of total exon DNA + RNA by next-generation sequencer (NGS) using biopsy material from 32 cases of fresh breast cancer showed that the number of gene mutations tended to be higher in triple-negative breast cancer. The number of gene mutations showed a positive correlation with TIL and PD-L1 expression rate (according to immunostaining IHC), T cell activation marker GZMB, and expected number of neoantigen candidates. Subsequently, the IFN-γ production of autologous lymphocytes against pulsed dendritic cells with the mutant peptide obtained by neoantigen predictive analysis was amplified in a peptide concentration-dependent manner. In addition, the cytotoxicity of lymphocytes stimulated with neoantigen-pulsed dendritic cells to autologous tumors was enhanced. These results suggest that neoantigen is an immune target in the breast cancer microenvironment.
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Academic Significance and Societal Importance of the Research Achievements |
NGSを用いた全エクソンDNA+RNAの解析の結果、乳癌におけるネオアンチゲンの存在を確認し、ネオアンチゲンで刺激されたTリンパ球よって腫瘍に対する細胞障害性は増強されることが示された。副作用の少ない精密個別化医療として細胞医薬への道を開いた社会的意義は大きい。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Validity of the prognostication tool PREDICT version 2.2 in Japanese breast cancer patients2021
Author(s)
Karen Zaguirre, Masaya Kai, Makoto Kubo, Mai Yamada, Kanako Kurata, Hitomi Kawaji, Kazuhisa Kaneshiro, Yurina Harada, Saori Hayashi, Akiko Shimazaki, Takafumi Morisaki, Hitomi Mori, Yoshinao Oda, Sanmei Chen, Taiki Moriyama, Shuji Shimizu, Masafumi Nakamura
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Journal Title
Cancer Medicine
Volume: 10
Issue: 5
Pages: 1605-1613
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] FoundationOne CDx gene profiling in Japanese pancreatic ductal adenocarcinoma patients: a single-institution experience2020
Author(s)
Kimura R, Ohtsuka T, Kubo M, Kajihara A, Fujii A, Watanabe Y, Mori Y, Ikenaga N, Nakata K, Shindo K, Ohuchida K,Nakamura M
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Journal Title
Surgery Today
Volume: 51
Issue: 4
Pages: 619-626
DOI
Related Report
Peer Reviewed
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[Journal Article] Microsatellite Instability in Japanese Female Patients With Triple-Negative Breast Cancer2020
Author(s)
Kurata K, Kubo M, Kai M, Mori H, Kawaji H, Kaneshiro K, Yamada M, Nishimura R, Osako T, Arima N, Okido M, Oda Y, Nakamura M
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Journal Title
Breast Cancer
Volume: 印刷中
Issue: 3
Pages: 490-498
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 乳癌におけるネオアンチゲン解析の有用性2020
Author(s)
久保真, 森崎隆史, 甲斐昌也, 梅林雅代, 島﨑亜希子, 林早織, 原田由利菜, 川地眸, 金城和寿, 倉田加奈子, 森瞳美, 山田舞, 森崎隆, 中村雅史
Organizer
第28回日本乳癌学会学術総会
Related Report
Invited
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[Presentation] マルチプレックス遺伝子パネルFoundationOne CDxが変えるHER2陽性乳癌の周術期治療2020
Author(s)
久保真, 川地眸, 甲斐昌也, 山田舞, 倉田加奈子, 森 瞳美, 金城和寿, 本山由利菜, 林早織, 島﨑亜希子, 森崎隆史, 沖英次, 中村雅史
Organizer
第120回日本外科学会定期学術集会
Related Report
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[Presentation] Tumor Mutational Burden in Japanese Patients with Triple Negative Breast Cancer2019
Author(s)
Kurata K, Kubo M, Yuan Y, Harada Y, Morisaki T, Shimazaki A, Hayashi S, Kawaji H, Kaneshiro K, Yamada M, Kai M, Nakamura M
Organizer
The 42nd San Antonio Breast Cancer Symposium
Related Report
Int'l Joint Research
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[Presentation] A prospective evaluation of comprehensive tumor profiling busing a targeted Next-generation sequencing for Japanese breast cancer patients2019
Author(s)
Kawaji H, Kubo M, Yamashita N, Harada Y, Shimazaki A, Hayashi S, Kurata K, Yamada M, Kaneshiro K, Kai M, Babe E, Oda Y, Nakamura M
Organizer
The 42nd San Antonio Breast Cancer Symposium
Related Report
Int'l Joint Research
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[Presentation] PD-L1 expression of tumor infiltrating immune cells has potential as a biomarker in triple-negative breast cancers2019
Author(s)
Harada Y, Kubo M, Mori H, Kai M, Yamada M, Kurata K, Kawaji H, Kaneshiro K, Hayashi S, Shimazaki A, Morisaki T, Yamaguchi R, Arima N, Nishimura R, Okido M, Nakamura M
Organizer
The 42nd San Antonio Breast Cancer Symposium
Related Report
Int'l Joint Research
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[Presentation] Transcription factor T-bet and PD-L1 expression in tumor microenvironment of triple-negative breast cancer2018
Author(s)
Hitomi Mori, Makoto Kubo, Masaya Kai, Kanako Kurata, Hitomi Kawaji, Kazuhisa Kaneshiro, Yurina Motoyama, Rumi Kuroki, Mai Yamada, Reiki Nishimura, Masayuki Okido, Yoshinao Oda, Masafumi Nakamura
Organizer
The 2018 San Antonio Breast Cancer Symposium
Related Report
Int'l Joint Research