• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Neoantigen analysis in tumor tissues for development of personalized precision cancer immunotherapy

Research Project

Project/Area Number 18K08577
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionKyushu 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.

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。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (16 results)

All 2021 2020 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results)

  • [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
    • Journal Title

      Cancer Medicine

      Volume: 10 Issue: 5 Pages: 1605-1613

    • DOI

      10.1002/cam4.3713

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive molecular profiling broadens treatment options for breast cancer patients2020

    • Author(s)
      Kawaji Hitomi、Kubo Makoto、Yamashita Nami、Yamamoto Hidetaka、Kai Masaya、Kajihara Atsuko、Yamada Mai、Kurata Kanako、Kaneshiro Kazuhisa、Harada Yurina、Hayashi Saori、Shimazaki Akiko、Mori Hitomi、Akiyoshi Sayuri、Oki Eiji、Oda Yoshinao、Baba Eishi、Mori Masaki、Nakamura Masafumi
    • Journal Title

      Cancer Medicine

      Volume: 10 Issue: 2 Pages: 529-539

    • DOI

      10.1002/cam4.3619

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Annual report of the Japanese Breast Cancer Society registry for 20162020

    • Author(s)
      Kubo Makoto、Kumamaru Hiraku、Isozumi Urara、Miyashita Minoru、Nagahashi Masayuki、Kadoya Takayuki、Kojima Yasuyuki、Aogi Kenjiro、Hayashi Naoki、Tamura Kenji、Asaga Sota、Niikura Naoki、Ogo Etsuyo、Iijima Kotaro、Tanakura Kenta、Yoshida Masayuki、Miyata Hiroaki、Yamamoto Yutaka、Imoto Shigeru、Jinno Hiromitsu
    • Journal Title

      Breast Cancer

      Volume: 27 Issue: 4 Pages: 511

    • DOI

      10.1007/s12282-020-01081-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      Surgery Today

      Volume: 51 Issue: 4 Pages: 619-626

    • DOI

      10.1007/s00595-020-02123-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      Breast Cancer

      Volume: 印刷中 Issue: 3 Pages: 490-498

    • DOI

      10.1007/s12282-019-01043-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Usefulness of the nCounter Analysis System to Monitor Immune-related Biomarkers in PBMCs During Anti-PD-1 Therapy2019

    • Author(s)
      MORISAKI TAKAFUMI、KUBO MAKOTO、UMEBAYASHI MASAYO、YUAN YUAN、TSUYADA AKIHIRO、TANAKA HIROTO、KOYA NORIHIRO、NAKAGAWA SHINICHIROU、MORISAKI TAKASHI、NAKAMURA MASAFUMI
    • Journal Title

      Anticancer Research

      Volume: 39 Issue: 8 Pages: 4517-4523

    • DOI

      10.21873/anticanres.13628

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] T-bet+ lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer2019

    • Author(s)
      Mori Hitomi、Kubo Makoto、Kai Masaya、Yamada Mai、Kurata Kanako、Kawaji Hitomi、Kaneshiro Kazuhisa、Osako Tomofumi、Nishimura Reiki、Arima Nobuyuki、Okido Masayuki、Kishimoto Junji、Oda Yoshinao、Nakamura Masafumi
    • Journal Title

      Breast Cancer Research and Treatment

      Volume: 176 Issue: 3 Pages: 569-577

    • DOI

      10.1007/s10549-019-05256-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [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
      2020 Annual Research Report
    • Invited
  • [Presentation] Precision Oncology:乳がんゲノムプロファイリングから見えてきたこと2020

    • Author(s)
      久保真, 甲斐昌也, 山田舞, 中村雅史
    • Organizer
      第26回日本遺伝性腫瘍学会学術集会
    • Related Report
      2020 Annual Research Report
  • [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
      2020 Annual Research Report
  • [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
      2019 Research-status Report
    • Int'l Joint Research
  • [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
      2019 Research-status Report
    • Int'l Joint Research
  • [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
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 乳癌におけるネオアンチゲン解析の意義2019

    • Author(s)
      森崎隆史、久保真、梅林雅代、吉村祥子、川地眸、倉田加奈子、金城和寿、森瞳、山田舞、林早織、本山由利菜、甲斐昌也、中村雅史、森崎隆
    • Organizer
      第32回日本バイオセラピィ学会学術集会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Microsatellite Instability in Triple Negative Breast Cancers2018

    • Author(s)
      Kanako Kurata, Makoto Kubo, Hitomi Mori, Hitomi Kawaji, Yurina Motoyama, Lumi Kuroki, Mai Yamada, Kazuhisa Kaneshiro, Masaya Kai, Masafumi Nakamura
    • Organizer
      The 2018 San Antonio Breast Cancer Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [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
      2018 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi