Rational design of the next-generation peptide immunotherapy which exploits tumor endothelial cells as an APC.
| Project/Area Number |
19K07775
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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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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Kochi University |
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Principal Investigator |
Udaka Keiko 高知大学, 教育研究部医療学系基礎医学部門, 教授 (40263066)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | MHC分子 / ペプチド / 腫瘍免疫 / Th / 機械学習 / 自己免疫疾患 / 血管内皮細胞 / 抗原提示 / CTL / クロスプレゼンテーション / T細胞 / 腫瘍 / 浸潤 / 抗原特異的 / HLA class II / peptide / Immunotherapy |
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| Outline of Research at the Start |
腫瘍血管内皮細胞（EC）の抗原提示能を活かして、腫瘍組織に腫瘍抗原特異的T細胞の浸潤を促す免疫療法を開発する。本研究では、以下の３つを達成したい。
１）機械学習を用いた、HLA class II-結合性ペプチドの予想platformの作製
２）ペプチド免疫によるTh、CTL誘導効率を高めるため、担体Mとペプチドおよびアジュバントを混ぜて皮内注射する方法を、Mなしの免疫と比較する。
３）人のペプチド免疫療法で誘導されがちな、アミノ酸変異のない腫瘍抗原に対するCTLについて、in vivoにおける抗腫瘍活性を検討する。また、より高い抗腫瘍活性を誘導する免疫法を開発する。
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| Outline of Final Research Achievements |
We have delineated an antigen-specific mechanism of T-cell infiltration into tumor tissues where endothelial cells act as antigen presenting cells (APCs). Tumor endothelial cells (tECs) present tumor antigen peptides in the context of MHC class I and class II molecules. A next-generation peptide immunotherapy which induces tumor-specific Th cells along with CTLs exhibited prominent anti-tumor responses. We further identified that a compound U2317 enhances cross presentation of tumor antigens by tECs. Since the performance of currently available platforms to predict MHC class II-binding peptides are quite limited we have first developed a method to measure MHC class II-peptide interactions accurately and then developed a computational platform to predict MHC class II-binding peptides. The resultant platforms could be used to identify epitope peptides for anti-tumor immunotherapy and investigation of autoimmune diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで治療効果に限界があった悪性腫瘍に対するペプチド免疫療法に、新たに明らかにした腫瘍抗原特異的なT細胞の浸潤機構を活用して治療効果を画期的に高め、動物実験では完治例も出る次世代ワクチンを開発した。この原理を利用すれば、自己免疫疾患の原因解明や制御のみならず、不用な非腫瘍性細胞を積極的に除去する新規治療法の開発も可能となる。
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Identification of Neoantigens in Two Murine Gastric Cancer Cell Lines Leading to the Neoantigen-Based Immunotherapy2022
Author(s)
Koji Nagaoka, Changbo Sun, Yukari Kobayashi, Takayuki Kanaseki, Serina Tokita, Toshihiro Komatsu, Kazuhiro Maejima, Junichiro Futami, Sachiyo Nomura, Keiko Udaka, Hidewaki Nakagawa, Toshihiko Torigoe, Kazuhiro Kakimi
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Journal Title
Cancers
Volume: 14
Issue: 1
Pages: 106-106
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Development of a novel monoclonal antibody that binds to most HLA-A allomorphs in a conformation-dependent yet peptide-promiscuous fashion2020
Author(s)
Toshihiro Komatsu, Takeyuki Shimizu, Makoto Kanoh, Tomoya Miyakawa, Yoko Satta, Yoshiki Yasukochi, Rika Fujimoto, Motoki Tada, Kaori Machida, Sayo Kataoka, Keiko Udaka
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Journal Title
Immunogenetics
Volume: 72
Issue: 3
Pages: 143-153
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of a Promiscuous Epitope Peptide Derived From HSP70.2019
Author(s)
Matsui H, Hazama S, Tamada K, Udaka K, Irie A, Nishimura Y, Miyakawa T, Doi S, Nakajima M, Kanekiyo S, Tokumitsu Y, Shindo Y, Tomochika S, Yoshida S, Iida M, Suzuki N, Takeda S, Yamamoto S, Yoshino S, Ueno T, Nagano H
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Journal Title
J Immunother
Volume: 42
Issue: 7
Pages: 244-250
DOI
Related Report
Peer Reviewed / Open Access
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