Basic construction of WT1-targetting CAR-T therapy for acute myeloid leukemia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09923
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Mie University
• Principal Investigator: Katayama Naoyuki 三重大学, 医学系研究科, 教授 (20185812)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 血液内科学 / 造血器腫瘍 / 急性骨髄性白血病 / 白血病幹細胞 / CD25 / 造血幹細胞 / B1細胞

Outline of Final Research Achievements

We examined leukemic stem cell (LSC) properties of CD25-positive acute myeloid leukemia (AML), using a patient-derived xenograft model and an in vitro culture system. The expression of CD25 fluctuated in LSCs in CD25-positive AML, suggesting that targeting CD25 may not be effective for eradicating LSCs of CD25-positive AML.
We analyzed peripheral blood cells from patients with paroxysmal nocturnal hemoglobinemia (PNH), a clonal disorder of hematopoietic stem cells (HSCs) caused by somatic mutations in PIGA. Importantly, the PIGA-mutated HSCs retain their multilineage differentiation capacity. We separated and investigated the mutated cells. The results suggest that a small, but distinct, proportion of B1 cells may be derived from adult HSCs. The similar data were obtained with peripheral blood cells from patients with chronic myelogenous leukemia, a clonal disorder of HSCs with their multilineage differentiation capacity except for T-cell lineage.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

造血器悪性腫瘍の中でがん幹細胞の存在が明白である急性骨髄性白血病（AML）に対する白血病幹細胞に対する分子標的療法の開発は、AMLの治療成績の改善に必須である。そのような状況の中では、標的分子の同定が必要とされ、その同定には緻密な検討が要求される。今回の研究成果は最適な分子の同定を再認識させる意義のあるものである。ヒトB1細胞の機能は不明な点も多い。この細胞の生物学的特性を明らかにしていくことで、様々な免疫反応や自己免疫疾患のメカニズムを検討していくことは、疾患の病態解明や治療法の開発に有用な情報を提供するものである。