Rational design of the next-generation peptide immunotherapy which exploits tumor endothelial cells as an APC.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07775
• 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: Kochi University
• 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)
• Project Period (FY): 2019-04-01 – 2022-03-31
• 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

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.

Free Research Field

腫瘍免疫

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。