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
نویسندگان
1 Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Hematology and Blood Bank, School of Allied Medical Science, Shahid Beheshti University of Medical Science, Tehran, Iran
4 Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Department of Hematology and Blood Bank, School of Allied Medical Science, Shahid Beheshti University of Medical Science, Tehran, Iran
6 Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
7 Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
8 Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
9 Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
doi
10.22074/cellj.2025.2057631.1827چکیده
Objective: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most effective treatment forpatients with high-risk acute myeloid leukemia (AML), but relapse remains a major challenge. Immunotherapy isconsidered a promising approach for reducing the risk of relapse. Natural killer (NK) cells exert cytotoxic effects againstmalignant cells, and their activation with interleukin-15 (IL-15) enhances anti-leukemic immune responses. This studyevaluated the safety and feasibility of in vitro IL-15 activation of CD56+ cells and assessed the safety of their infusionin AML patients following allo-HSCT.Materials and Methods: In this phase I clinical trial study, CD56+ cells were isolated from non-mobilized donors usinga one-step CD56 enrichment protocol to obtain NK and NKT cells. CD56+ cells were activated by overnight incubationwith IL-15. A cytotoxicity assay was performed against K562 cells. Three escalating doses of CD56+ cells consistingof 1×106, 3×106, and 5×106 cells/kg of patient bodyweight were infused to the three patients on days +7, +14, and +21post-allo-HSCT. Patients were observed during and up to 4 hours after the infusion for immediate adverse events andwere 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+ cellswas higher than that of non-activated CD56+ cells. This method was safe and no intervention-related complicationswere 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 confirmand validate the current hypothesi (registration number: IRCT20230801058996N2).
