Feasibility and Safety of IL-15-Activated CD56+ Cell Therapy in High-Risk Acute Myeloid Leukemia after Hematopoietic Stem Cell Transplantation: Phase I Clinical Trial.

[OBJECTIVE] 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 IL-15 activation of CD56 cells and assessed the safety of their infusion in AML patients following allo-HSCT.

[MATERIALS AND METHODS] 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, 3×10, and 5×10 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.

[RESULTS] 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.

[CONCLUSION] 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).