Development of immunotherapy against malignancies relapsed post-transplant using TCR-T cells specific for mismatched HLAs

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08341
• 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: Nagoya University
• Principal Investigator: AKATSUKA YOSHIKI 名古屋大学, 医学系研究科, 特任教授 (70333391)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: HLA-DP / アロ抗原 / 同種造血幹細胞移植 / 移植後再発白血病 / 養子細胞免疫療法

Outline of Final Research Achievements

We attempted to generate T cell clones specific for mismatched HLA-DP molecules from peripheral blood T cells of healthy volunteers and patients who underwent HLA-DP-mismatched allogeneic hematopoietic cell transplantation from their unrelated donor. Several clones specific for HLA-DPB1*09:01and DPB1*02:01 were isolated from the volunteers' blood and those specific for DPB1*09:01 were isolated from the patients. The former clones showed weak reactivity against DPB1*09:01-positive primary leukemic blasts from various patients while the latter clones showed significant IFN-γ production and cytotoxicity toward the same targets. Healthy T cells that were gene-modified with a retrovirus encoding T cell receptor cDNA of the DPB1*09:01-specific T cell clone successfully demonstrated the identical specificity and cytokine production capacity against the cognate target cells.

Free Research Field

血液免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究を通じて樹立されたT細胞クローンが認識するHLA-DPB1*09:01およびDPB1*02:01は日本人間の同種造血細胞移植で不適合が起こりやすいHLA-DP型を認識するものであった。難治性白血病患者がこれらのHLA-DP座が不適合のドナーより移植を受けた後に再発してしまった場合、今回樹立したクローンやそのT細胞受容体遺伝子を導入されたT細胞を患者に投与することで、再発した白血病に対して抗原特異的な養子免疫細胞療法となると期待される。今後さらに日本人に多い3種類程度のHLA-DP型に特異的なT細胞クローンを樹立することで、約7割程度の患者に免疫療法をすることが可能となると考えられる。