CELL INTELLIGENCE · 肿瘤细胞治疗研究

Cord blood (CB)-derived chimeric antigen receptor (CAR)-natural killer (NK) cells targeting CD19 have been shown to be effective against B cell malignancies. While human CD56 + NK cells can be expanded in vitro , NK cells can also be differentiated from hematopoietic progenitor cells. It is still unclear whether CAR-NK cells originate from mature NK cells or NK progenitor cells in CB. Here, we determined that CAR-NK cells were predominantly derived from CD56 - NK progenitor cells. We first found that substantial numbers of CD19 CAR-NK cells were produced from CD56 - CB mononuclear cells after in vitro culture for 2 weeks. Single-cell RNA sequencing analysis of CD56 - CD3 - CD14 - CD19 - CB mononuclear cells revealed that these cells could be subdivided into three subpopulations based on the expression of CD34 and human leukocyte antigen (HLA)-DR. NK cells originated primarily from CD34 - HLA-DR - cells. In addition, among the CD34 - HLA-DR - cells, only CD7 + cells could differentiate into NK cells. These results indicate that CD56 - CD7 + CD34 - HLA-DR - lineage marker (Lin) - cells are the major origin of human CB-derived CAR-NK cells, indicating the importance of developing methods to enhance the quality and quantity of NK cells produced from these NK progenitor cells.