Repertoirome analysis of antibody genes of peripheral blood memory B cells for qualitative evaluation of tumor associated immune response

• Project/Area Number: 18K07334
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Hoshi University
• Principal Investigator: Tsuiji Makoto 星薬科大学, 薬学部, 准教授 (90302611)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: がん免疫 / 免疫状態 / 抗体 / レパトア / 免疫記憶 / バイオマーカー / 末梢血 / scFv-Fc / がん / T細胞抗原受容体 / 可変部 / 記憶B細胞 / 抗体遺伝子

Outline of Final Research Achievements

In cancer-bearing model mice, the abundance ratio of B220-positive and CD4-positive cells in peripheral blood changes correlate with increasing tumor volume.
It also clarified the changes in the repertoire of the variable region of antibody genes (BCRs) and the α chain and β chain of T cell receptor genes (TCRs).
Furthermore, to verify their binding specificity, we constructed the single-chain antibody (scFv-Fc) and scTCR-Fc. In the future, we plan to continue building a platform to utilize the obtained variable part as a new molecular-targeted drug discovery drug.

Academic Significance and Societal Importance of the Research Achievements

抗体医薬品、がんワクチン、免疫療法などの選択基準や治療の継続性の判断基準が不足している現在、個別の免疫状態に対応したプレシジョン医療への移行が求められている。そこで担がんモデルマウスにて、独自に確立した免疫応答の質的評価となるB細胞とT細胞の可変部領域の多様性解析を進めたところ、免疫状態に応じて変化することを明らかにした。さらにそれらの抗原認識特異性を明らかにするために一本鎖抗体(scFv-Fc)およびscTCR-Fcの構築に成功した。今後は、得られた可変部を新たな分子標的医薬品として創薬に活用することを目指しプラットフォームの構築を展開する予定である。

Research Products

• [Journal Article] rs9459874 and rs1012656 in CCR6/FGFR1OP confer susceptibility to primary biliary cholangitis (2022)
  • Author(s): Hitomi Yuki、Aiba Yoshihiro、Ueno Kazuko、Nishida Nao、Kawai Yosuke、Kawashima Minae、Yasunami Michio、Gervais Olivier、Ito Masahiro、Cordell Heather J.、Mells George F.、Nagasaki Masao、Tokunaga Katsushi、Tsuiji Makoto、Nakamura Minoru
  • Journal Title: Journal of Autoimmunity Volume: 126 Pages: 102775-102775
  • DOI: 10.1016/j.jaut.2021.102775
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Coronin-1 is phosphorylated at Thr-412 by protein kinase Cα in human phagocytic cells (2021)
  • Author(s): Oku Teruaki、Kaneko Yutaka、Ishii Rie、Hitomi Yuki、Tsuiji Makoto、Toyoshima Satoshi、Tsuji Tsutomu
  • Journal Title: Biochemistry and Biophysics Reports Volume: 27 Pages: 101041-101041
  • DOI: 10.1016/j.bbrep.2021.101041
  • Peer Reviewed / Open Access
• [Journal Article] Immunomodulatory Activity of an Aqueous Extract of Mycelium of an Endophytic-Like Fungus, Ustilago esculenta (2021)
  • Author(s): Makoto Tsuiji, Junko Nagasaka, Yoshimasa Yajima, Keita Nishiumi, Yasutaka Kojima, Miho Amemiya, Wakana Ogura, Takaaki Moriyama, Tomoko Sakai, Teruaki Oku, Tsutomu Tsuji
  • Journal Title: BPB Reports Volume: 4 (4) Pages: 98-102
  • NAID: 130008069606
  • Peer Reviewed
• [Journal Article] rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis (2021)
  • Author(s): Hitomi Yuki、Aiba Yoshihiro、Kawai Yosuke、Kojima Kaname、Ueno Kazuko、Nishida Nao、Kawashima Minae、Gervais Olivier、Khor Seik-Soon、Nagasaki Masao、Tokunaga Katsushi、Nakamura Minoru、Tsuiji Makoto
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 4557-4557
  • DOI: 10.1038/s41598-021-84042-x
  • Peer Reviewed / Open Access
• [Journal Article] Reply to Slominski et al.: UVB irradiation induces proenkephalin+ regulatory T cells with a wound-healing function (2021)
  • Author(s): Shime Hiroaki、Odanaka Mizuyu、Tsuiji Makoto、Matoba Takuma、Imai Masaki、Yasumizu Yoshiaki、Uraki Ryuta、Minohara Kiyoshi、Watanabe Maiko、Bonito Anthony John、Fukuyama Hidehiro、Ohkura Naganari、Sakaguchi Shimon、Morita Akimichi、Yamazaki Sayuri
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 118 Issue: 3
  • DOI: 10.1073/pnas.2021919118
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Guillain-Barre syndrome-associated SIGLEC10 rare variant impairs its recognition of gangliosides (2021)
  • Author(s): Alborzian Deh Sheikh Amin、Gomaa Soha、Li Xuexin、Routledge Matthew、Saigoh Kazumasa、Numoto Nobutaka、Angata Takashi、Hitomi Yuki、Takematsu Hiromu、Tsuiji Makoto、Ito Nobutoshi、Kusunoki Susumu、Tsubata Takeshi
  • Journal Title: Journal of Autoimmunity Volume: 116 Pages: 102571-102571
  • DOI: 10.1016/j.jaut.2020.102571
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Proenkephalin+regulatory T cells expanded by ultraviolet B exposure maintain skin homeostasis with a healing function (2020)
  • Author(s): Shime Hiroaki、Odanaka Mizuyu、Tsuiji Makoto、Matoba Takuma、Imai Masaki、Yasumizu Yoshiaki、Uraki Ryuta、Minohara Kiyoshi、Watanabe Maiko、Bonito Anthony John、Fukuyama Hidehiro、Ohkura Naganari、Sakaguchi Shimon、Morita Akimichi、Yamazaki Sayuri
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 117 Issue: 34 Pages: 20696-20705
  • DOI: 10.1073/pnas.2000372117
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] がん病態関連免疫応答の質的評価のための末梢血記憶B細胞抗体遺伝子レパトローム解析 (2019)
  • Author(s): 築地信
  • Journal Title: Medical Science Digest Volume: Vol.45 No.2 Pages: 14-15
• [Journal Article] がん病態関連免疫応答の質的評価のための末梢血記憶B細胞抗体遺伝子レパトローム解析 (2019)
  • Author(s): 築地信
  • Journal Title: Precision Medicine Volume: Vol.2 No.2 Pages: 79-81
• [Presentation] 腫瘍関連糖鎖抗原を認識する抗体の可変部遺伝子配列の決定と人工抗体の作製 (2022)
  • Author(s): 吉田 昌宏、稲垣 優希、人見 祐基、奥 輝明、伝田 香里、入村 達郎、築地 信
  • Organizer: 日本薬学会年会 142年会
• [Presentation] 免疫細胞特異的アクチン結合タンパク質Coronin-1の発現制御機構の解析 (2022)
  • Author(s): 安藤 祐介、金子 豊、長谷川 晋也、築地 信、渡辺 知恵、奥 輝明
  • Organizer: 日本薬学会年会 142年会
• [Presentation] MUC1糖ペプチドと抗MUC1抗体MY.1E12の相互作用解析 (2022)
  • Author(s): 國府 涼香、倉谷 太豪、高橋 優花、大野 詩歩、真鍋 法義、清水 弘樹、千葉 靖典、伝田 香里、築地 信、入村 達郎、山口 芳樹
  • Organizer: 日本薬学会年会 142年会
• [Presentation] Lacto-N-fucopentaose Iの立体構造および抗iPS細胞抗体R-17Fとの相互作用の解析 (2022)
  • Author(s): 大野 詩歩、大内 陽翔、齋藤 祐希、真鍋 法義、湯浅 徳行、松崎 祐二、築地 信、川嵜 敏祐、山口 芳樹
  • Organizer: 日本薬学会年会 142年会
• [Presentation] 糖鎖抗原を認識する抗体の可変部遺伝子配列の決定と人工抗体の作製 (2022)
  • Author(s): 築地 信、吉田 昌宏、稲垣 優希、石村 彰識、河村 桂輔、獅子原 弘樹、伝田 香里、入村 達郎、中尾 広美、川嵜 敏祐
  • Organizer: 第6回 糖鎖免疫学研究会
• [Presentation] Variable gene repertoirome analysis of peripheral blood BCRs and CD4+ T cell TCRs(alpha/beta) for monitoring of tumor-associated immune responses (2021)
  • Author(s): Makoto Tsuiji
  • Organizer: 第50回 日本免疫学会
• [Presentation] Proenkephalin+ regulatory T cells expanded by ultraviolet B exposure maintain skin homeostasis with a healing function (2021)
  • Author(s): Hiroaki Shime, Mizuyu Odanaka, Makoto Tsuiji, Masaki Imai, Yoshiaki Yasumizu, Ryuta Uraki, Anthony JB, Hidehiro Fukuyama, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita, Sayuri Yamazaki
  • Organizer: 第50回 日本免疫学会
• [Presentation] Skin regulatory T cells expanded by ultraviolet B exposure have a unique gene expression profile compared to other tissue Treg cells (2021)
  • Author(s): Mizuyu Odanaka, Hiroaki Shime, Makoto Tsuiji, Masaki Imai, Yoshiaki Yasumizu, Ryuta Uraki, Anthony JB, Hidehiro Fukuyama, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita, Sayuri Yamazaki
  • Organizer: 第50回 日本免疫学会
• [Presentation] Evaluation of immune responses induced by influenza vaccines using antibody repertoire analysis (2021)
  • Author(s): Kayoko Sato, Hideki Asanuma, Makoto Tsuiji
  • Organizer: 第50回 日本免疫学会
• [Presentation] NKT-mediated vaccine induces affinity maturation of BCR and supply antibody dependent protection against Streptococcus pneumoniae (2021)
  • Author(s): Koji Hayashizaki, Shogo Takatsuka, Yasuhiro Kamii, Makoto Tsuiji, Masato Kubo, Yoshimasa Takahashi, Yuki Kinjo
  • Organizer: 第50回 日本免疫学会
• [Presentation] Identification of the primary functional variants in primary biliary cholangitis susceptibility gene CCR6/FGFR1OP (2021)
  • Author(s): Yuki Hitomi, Yoshihiro Aiba, Makoto Tsuiji, Minoru Nakamura
  • Organizer: 第50回 日本免疫学会
• [Presentation] Variable gene repertoirome analysis of peripheral blood BCRs and CD4+ T cell TCRs(alpha/beta) for monitoring of tumor-associated immune responses (2021)
  • Author(s): Makoto Tsuiji
  • Organizer: 2021 JCA-AACR Precision Cancer Medicine International Conference
• [Presentation] 糖鎖抗原を認識する抗体の可変部遺伝子配列の決定と人工抗体の作製 (2021)
  • Author(s): 築地 信、吉田 昌宏、稲垣 優希、石村 彰識、河村 桂輔、獅子原 弘樹、伝田 香里、入村 達郎、中尾 広美、川嵜 敏祐
  • Organizer: 第40回 日本糖質学会年会
• [Presentation] 潰瘍性大腸炎モデルマウスの大腸粘膜固有層に集積する細胞へのブシラミンの効果 (2021)
  • Author(s): 柳澤 直樹、菊池 隼矢、奥 輝明、築地 信
  • Organizer: 第21回 Pharmaco-Hematology シンポジウム
• [Presentation] 腫瘍関連抗原を認識する抗体の可変部遺伝子配列の決定と人工抗体の作製 (2020)
  • Author(s): 築地信, 澁澤晴美, 岡部早希子, 林美佑, 稲垣優希, 吉田昌宏, 人見祐基, 奥輝明, 伝田香里, 入村達郎
  • Organizer: 日本薬学会年会140th
• [Presentation] ヒト由来細胞を利用した新規発熱性物質試験法の開発 (2020)
  • Author(s): 奥輝明, 安藤祐介, 人見祐基, 築地信, 亀井淳三, 林克彦, 菊池裕, 菊池裕, 工藤由起子, 伊豆津健一, 辻勉
  • Organizer: 日本薬学会年会140th
• [Presentation] 糖鎖認識抗体によるエピトープ認識の分子基盤 (2020)
  • Author(s): 川嵜敏祐, 中尾広美, 川嵜伸子, 築地信, 稲垣優希, 吉田昌宏, 山口芳樹, 天野裕之, 大野詩歩, 真鍋法義
  • Organizer: 日本生化学会大会93rd
• [Presentation] Variable gene repertoirome analysis of peripheral blood BCRs and CD4+ T cell TCRs(alpha/beta) for monitoring of cancer-associated immune responses (2019)
  • Author(s): Makoto Tsuiji
  • Organizer: 第48回 日本免疫学会学術集会
• [Presentation] 担がんマウスにおける免疫状態を評価するための末梢血B細胞およびT細胞の抗原受容体遺伝子レパトローム解析 (2019)
  • Author(s): 築地信、岡部早希子、澁澤晴美、林美佑
  • Organizer: 第92回 日本生化学会大会
• [Presentation] Antibody gene repertoirome analysis of peripheral blood B cells for quantitative evaluation of cancer-associated immune response (2018)
  • Author(s): M. Tsuiji, S. Okabe, H. Shibusawa, T. Yamaguchi, Y. Hayakawa, T. Tsuji
  • Organizer: The 6th JCA-AACR Special Joint Conference
  • Int'l Joint Research
• [Presentation] 担がんマウスにおける末梢血B細胞の抗体遺伝子レパトローム解析 (2018)
  • Author(s): 築地信、岡部早希子、澁澤晴美、山口大樹、早川侑希、辻勉
  • Organizer: 第19回 Pharmaco-Hematologyシンポジウム
• [Presentation] Variable gene repertoirome analysis of peripheral blood BCRs and CD4+ TCRs (a/b) for qualitative evaluation of cancer-associated immune response (2018)
  • Author(s): M. Tsuiji, S. Okabe, H. Shibusawa, T. Yamaguchi, Y. Hayakawa, T. Tsuji
  • Organizer: 第47回 日本免疫学学術集会
• [Remarks] Makoto Tsuiji (Researchmap)
  • URL: https://researchmap.jp/tsuijimak
• [Remarks] Makoto Tsuiji (Researchgate)
  • URL: https://www.researchgate.net/profile/Makoto-Tsuiji
• [Remarks] Makoto Tsuiji (Orcid)
  • URL: https://orcid.org/0000-0002-5607-4880
• [Remarks] Makoto Tsuiji (Loop)
  • URL: https://loop.frontiersin.org/people/1498398/overview