Development of CRISPR/HDR genome editing technology in primary T cells for improved immunotherapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07212
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Chiba University
• Principal Investigator: OUCHI YASUO 千葉大学, 大学院医学研究院, 特任助教 (70553858)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ゲノム編集 / T細胞 / がん免疫療法

Outline of Final Research Achievements

Recently, immunotherapies have led to the successful development of novel treatments for cancer, primarily by two strategies, immunologic checkpoint blockade therapy, and adoptive T-cell therapy. Although these immunotherapies have shown promising efficacy in the treatment of cancer, there remain considerable difficulties. In this study, to develop the clinically applicable methodology for the immunotherapies using genome-edited T cells, we aim to develop the technology that allows the one-step generation of antigen-specific T cells using non-viral strategy. From the results obtained in this study, we developed a novel nanoparticle carrying genome editing tool for the primary mouse T cells. This technology allows a novel and easy-to-use methodology to generate the genome-edited T cells for use in clinical settings that have been previously impossible.

Free Research Field

ゲノム編集技術

Academic Significance and Societal Importance of the Research Achievements

近年、免疫チェックポイント阻害剤、ゲノム編集T細胞、がん抗原特異的TCRまたはキメラ抗原受容体(CAR)遺伝子導入T細胞を用いたがん免疫療法は第四の治療法として注目されている。しかし、ゲノム編集技術を用いた免疫細胞療法は国外では臨床試験が進んでいるものの、数多くの技術的な問題を抱えており、幅広い臨床応用は難しい状況である。本研究課題で開発したナノ粒子を利用したゲノム編集技術は従来の遺伝子導入試薬では不可能であった初代T細胞に対する簡便な遺伝子導入およびゲノム編集を可能にする技術である。今後、ゲノム編集T細胞を用いた免疫細胞療法の汎用化において重要なツールになることが期待できる。