Analysis of cancer antigens through novel HLA assay

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22551
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Miyadera Hiroko 筑波大学, 医学医療系, 助教 (40361464)
• Co-Investigator(Kenkyū-buntansha): 平山 令明 東海大学, 先進生命科学研究所, 教授 (70238393)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: HLA / MHC / がん抗原 / ワクチン

Outline of Final Research Achievements

We developed a protocol to measure the ability of each HLA allele to present peptide on cell-surface. In the present study, we validated the protocol, analyzed the binding data for known T-cell epitopes, and compared the binding spectra obtained from in silico prediction. In addition, we improved the method to construct expression plasmids to enable large scale analysis at relatively low-cost. The preliminary data suggest that our method is superior than known assays in terms of its ability to predict potential epitopes. We then utilized this method to analyze the interaction of murine MHC and cancer neoepitopes. These data are under submission, or under preparation for submission.

Free Research Field

生化学、免疫学

Academic Significance and Societal Importance of the Research Achievements

HLA(ヒト白血球抗原)は獲得免疫応答をつかさどるタンパク質である。HLAが、がん特異的な変異を含むペプチド断片を結合し、細胞表面に提示すると、がん細胞を標的とした免疫応答が起こりうる。そのような免疫応答を引き起こすペプチドを見出すことが出来れば、効果の高いペプチドワクチンの設計につながるが、現状では、がんペプチドワクチンは少数の著効例がある一方、全体の奏効率は低い。この現状を打開するため研究代表者はHLAクラスIIが提示するペプチド探索手法を開発し、測定系の評価、がん抗原への適用を行った。本研究は、がんペプチドワクチンをすべての患者に対して設計できる体制の構築に貢献する。