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2022 Fiscal Year Final Research Report

Establishment of the TCR-T cell therapy for adult T-cell leukemia/lymphoma

Research Project

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Project/Area Number 18K16095
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionNagoya City University

Principal Investigator

Masaki Ayako  名古屋市立大学, 医薬学総合研究院(医学), 准教授 (40648044)

Project Period (FY) 2018-04-01 – 2023-03-31
KeywordsATLL / TCR-T
Outline of Final Research Achievements

For establishment of the TCR-T therapy for adult T-cell lymphoma/leukemia, we investigate the factors suppressing antitumor immune responses, and evaluated the activity of NY-EOS-1 specific TCR-T cells. We demonstrated that the percentage of PD-1-positive Tax-CTL was inversely correlated with their function in ATL patients. We found NY-ESO-1 expression in some of ATL patients, and confirmed activity of the NY-EOS-1 specific TCR-T cells against epitope peptide and NY-ESO-1-positive cell line in vitro. The activity of NY-EOS-1 specific TCR-T tended to decrease in the high-kynurenine and low-tryptophan culture medium.

Free Research Field

Lymphoma

Academic Significance and Societal Importance of the Research Achievements

ATLに対するTCR-T療法は、ドナー確保が容易で、移植片対宿主病に伴うさまざまな合併症を抑制することができるため、幅広い年齢の患者に対して安全に使用できる治療となることが期待できる。
本研究では患者由来ATL細胞でのNY-ESO-1発現と、NY-ESO-1特異的TCR-Tがepitope peptideおよび細胞株を認識して細胞障害活性を発揮することを見出し、NY-ESO-1特異的TCR-T療法の有望性を示した。また、ATL患者由来の腫瘍特異的CTLにおけるPD-1発現とサイトカイン産生の減弱の関連を見出した。ATLに対する免疫チェックポイント阻害剤の有効性が示唆された。

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Published: 2024-01-30  

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