Development of novel cancer immunotherapy based on memory-oriented TCR

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07216
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Osaka University
• Principal Investigator: Morimoto Soyoko 大阪大学, 医学系研究科, 寄附講座助教 (10649023)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: メモリー / TCR functional avidity / WT1

Outline of Final Research Achievements

In our previous reports, we demonstrated that induction and maintain of tumor-antigen specific-memory T cells in vivo needed to successful treatment of cancer immunotherapy and that TCR avidity have played an essential role in differentiation of naive T cells to memory T cells. To evaluate accurately of TCR avidity, we tried to establish the platform cell that could reflect the function of TCR-transduced T cells. TCR avidity evaluated by TCR-transduced platform cells correlated with cytokine production, cell proliferation, and cytotoxic activity of TCR-transduced T cells. These results showed that the platform cell was a novel and stable tool for the efficient and precise evaluation of the functional avidity of isolated and transduced TCRs in developing TCR-base immunotherapy.

Free Research Field

癌免疫学

Academic Significance and Societal Importance of the Research Achievements

近年の技術的発展に伴い、TCR遺伝子治療に用いるTCRの選択肢が大幅に広がった。しかしながら、治療に最良のTCRを選択する方法が無かった。本研究で作製したplatform細胞を用いることで、簡便かつ正確にTCR導入T細胞の機能を反映したTCR avidityを評価でき、最良のTCR選択が可能となる。さらに、platform細胞作製に用いた実験系を応用することで、TCR分化決定因子としてのTCR signalやそれに伴う遺伝子発現の差を評価することも可能となる。これは、TCR遺伝子治療のみならずがん免疫療法全般に対して治療効果改善の一端を担う可能性を大いに示唆する。