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2020 Fiscal Year Final Research Report

Identification of mutation-derived spliced peptides

Research Project

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Project/Area Number 18K19458
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionSapporo Medical University

Principal Investigator

Torigoe Toshihiko  札幌医科大学, 医学部, 教授 (20301400)

Project Period (FY) 2018-06-29 – 2021-03-31
Keywordsがん抗原 / スプライスペプチド / プロテアゾーム / 抗原提示 / がんワクチン / がん免疫療法 / T細胞 / HLA
Outline of Final Research Achievements

We could successfully develop the de novo sequencing technology for HLA ligandome analysis, and discovered three spliced peptides derived from wild-type proteins in HCT15 colon cancer cells. Spliced peptide-specific cytotoxic T-cells (CTLs) were induced from peripheral blood lymphocytes of healthy donors by mixed lymphocyte-peptide culture. Two CTL clones were established and analyzed for the cytotoxic potentials, indicating that the novel spliced peptides were highly immunogenic. Then, we analyzed the mechanism of peptide splicing, indicating that the splicing was dependent on the activity of proteasome in the cells. Our data revealed the novel category of neoantigens, which might contribute to the development of a prophylactic cancer vaccine as well as a therapeutic cancer vaccine.

Free Research Field

分子免疫病理学

Academic Significance and Societal Importance of the Research Achievements

本研究で最大の学術的意義は、ヒト大腸がん細胞から新規スプライスペプチドを同定し、抗原特異的CTLクローンの樹立に成功した点にある。親タンパクはがん細胞だけでなく、正常組織にも発現しているハウスキーピング分子である。それにも関わらず、スプライスペプチドの高い免疫原性が確認されたことは、この分子のスプライスががん細胞特異的に生じている可能性を示唆する結果であり、遺伝子変異に依存しない新しいネオアンチゲンの産生メカニズムとして大きな細胞生物学的意義がある。また、患者に共通して適応されるネオアンチゲンワクチン創薬に貢献することが期待され、今後がん予防ワクチンの実用化にも道が拓かれる可能性もある。

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Published: 2022-01-27  

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