CELL INTELLIGENCE · 肿瘤细胞治疗研究

OBJECTIVES: Leukemia stem cells (LSCs) in chronic myeloid leukemia (CML) are associated with disease recurrence and progression, cannot be eliminated by tyrosine kinase inhibitors (TKIs), and affect TKI discontinuation in CML patients. Chimeric antigen receptor T cells (CAR-T) therapy can eliminate tumor cells expressing specific antigens. CD7 is highly expressed on LSCs and can distinguish LSCs from normal hematopoietic stem cells (HSCs). This study explored the biological characteristics of CD7, and evaluated the effects of CD7 CAR-T cells on CD7 + CML tumor cells and CD7 + LSCs in vitro. METHODS: We examined CD7 expression in primary CML LSCs, constructed CD7-overexpressing K562 cells, and assessed the in vitro cytotoxicity, degranulation and cytokine secretion of CD7 CAR-T cells against CD7 + CML cells and CD34 + CD7 + LSCs, along with the correlation between CD7 and TKI resistance. RESULTS: CD7 + CML tumor cells were resistant to TKI to a certain extent. This molecule appears to be relevant to the survival of LSCs in patients with CML receiving TKI-targeted therapy. In the in vitro co-culture system, CD7 CAR-T cells effectively eliminate CD7 + CML cells and LSCs and exhibit multiple immunological activities during the co-culture process. DISCUSSION: This study targets the key limitation of current CML treatment in that TKIs fail to eliminate LSCs, and confirms the correlation between CD7 and LSC survival, as well as the targeting potential of CD7 CAR-T for CML. CONCLUSION: This study showed that using CD7 CAR-T cells to specifically eliminate LSCs is effective and rational in vitro, which provides experimental evidence for LSC-targeted CML therapy and lays a foundation for subsequent in vivo and translational research.