TALEN-mediated genome editing facilitates establishing universal genome-edited regulatory T cells for immunotherapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08838
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Fujita Health University (2021); Hiroshima University (2019-2020)
• Principal Investigator: Takakazu Kawase 藤田医科大学, 国際再生医療センター, 准教授 (30463194)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: T細胞受容体 / ゲノム編集 / 養子免疫療法

Outline of Final Research Achievements

By utilizing genome editing technology using TALEN, we investigated the production of genome-edited T cells that suppress the risk of unexpected immune reactions due to T cell receptor (TCR) mispairing between introduced and endogenous TCR α and β chains. We established a method for knocking out the endogenous TCR and knocking in the desired antigen-specific TCR, and examined the cytotoxic activity of the produced antigen-specific genome-edited T cells in vitro. The method initially investigated was able to confirm antigen-specific cytotoxicity in vitro, but the viability of the cells was poor. Therefore, we investigated a method to minimize the number of gene transfer steps to reduce cell damage, and established a method to precisely introduce the desired gene into the targeted genomic site in two steps.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究をとおして、T細胞への遺伝子導入の際のダメージ軽減のために、2ステップで目的の遺伝子をゲノムの目的の位置に遺伝子導入する方法を確立できた。本方法により、抗原特異的TCRのα鎖とβ鎖を非特異的T細胞に遺伝子導入することにより、養子免疫T細胞療法に活用できる、安全でviabilityの高いTCR-T細胞を作成できることが期待される。