Development of novel redirected T cell-based adaptive immunotherapy to cure the chemotherapy-resistant leukemia

• Project/Area Number: 16K19577
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Ehime University
• Principal Investigator: ASAI HIROAKI 愛媛大学, 医学部附属病院, 講師(病院教員) (00726838)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 遺伝子改変T細胞療法 / Wilms tumor 1 / PD-L1 / PD1 / チェックポイント阻害剤 / PD-1 / 免疫チェックポイント阻害剤 / 細胞免疫療法 / WT1 / 化学療法抵抗性白血病

Outline of Final Research Achievements

We achieved the development of novel redirected HLA-A24-restricted CD8+T-cell based adoptive immunotherapy targeting Wilms tumor 1(WT1) which strengthened affinity and safety. On the one hand, leukemia cells express PD-L1 under the presence of IFN-γ, but at the same time HLA-A24-restricted WT1-CTLs express PD-1. This result support the existence of PD-L1/PD-1 axis between leukemia cells and A24/WT1-TCR-CTLs. Thus, our experimental findings strongly suggest that we can enhance the clinical efficacy of redirected T cell based adaptive immunotherapy by using adjunctively with anti-PD-1/PD-L1 monoclonal antibodies.