IL-15 激活的 CD56+细胞疗法在高危急性髓系白血病造血干细胞移植后的可行性与安全性：I 期临床试验

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most effective treatment for patients with high-risk acute myeloid leukemia (AML), but relapse remains a major challenge. Immunotherapy is considered a promising approach for reducing the risk of relapse. Natural killer (NK) cells exert cytotoxic effects against malignant cells, and their activation with interleukin-15 (IL-15) enhances anti-leukemic immune responses. This study evaluated the safety and feasibility of in vitro IL-15 activation of CD56 + cells and assessed the safety of their infusion in AML patients following allo-HSCT.

In this phase I clinical trial study, CD56 + cells were isolated from non-mobilized donors using a one-step CD56 enrichment protocol to obtain NK and NKT cells. CD56 + cells were activated by overnight incubation with IL-15. A cytotoxicity assay was performed against K562 cells. Three escalating doses of CD56 + cells consisting of 1×10 6 , 3×10 6 , and 5×10 6 cells/kg of patient bodyweight were infused to the three patients on days +7, +14, and +21 post-allo-HSCT. Patients were observed during and up to 4 hours after the infusion for immediate adverse events and were monitored for 21 days to detect delayed events.

Activation with IL-15 increased the expression of activating receptors, including CD25, CD69, NKp30, NKp46, and NKG2D decreased the expression of the inhibitory receptor NKG2A. The cytotoxicity of IL-15-activated CD56 + cells was higher than that of non-activated CD56 + cells. This method was safe and no intervention-related complications were observed.

We identified a feasible method to activate CD56 + cells and evaluate the safety of their infusion in patients. Despite the value of activating CD56 + cells with IL-15, further studies with larger sample sizes are needed to confirm and validate the current hypothesi (registration number: IRCT20230801058996N2).