Cord blood donor characteristics determine the efficacy of IL-15 armored CAR-transduced natural killer cells against CD19-positive B cell tumors

We conducted a phase I-II clinical trial at our institution that was designed to assess the safety and efficacy of escalating doses of CAR19/IL-15 CB-NK cells as treatment for relapsed/refractory CD19-positive malignancies. NK cells from these optimal CBs were highly functional and enriched in effector-related genes. In contrast, NK cells from suboptimal CBs had upregulation of inflammation, cellular stress and apoptosis programs. Finally, using multiple mouse models, we confirmed the superior anti-tumor activity of CAR-NK cells from optimal CBs. The objective of this study was to investigate the molecular profiles difference between suboptimal and optimal CBs.