Assessment of safety and feasibility of allogeneic NKG2DL-specific CAR-NK cells in patients with relapsed or refractory acute myeloid leukemia
YANG Yuanlin
FEI Xiaoming
LEI Fang
JI Yanping
TANG Yu
Abstract：Objective To investigate the expression of NKG2D ligands(NKG2DLs)on leukemia cells in patients with acute myeloid leukemia(AML),and to preliminarily explore the safety and feasibility of umbilical cord blood-derived NKG2DL-targeting chimeric antigen receptor natural killer cells(CAR-NK)in the treatment of relapsed/refractory AML(RR-AML)patients.Methods Flow cytometry was used to detect NKG2DLs expression on tumor cells in AML patients admitted to the Affiliated Hospital of Jiangsu University between January 2023 and March 2024.Three patients with RR-AML were enrolled and treated with umbilical cord blood-derived NKG2D ligand-targeting CAR-NK cells following lymphodepleting chemotherapy.Results A total of 28 AML patients were enrolled in this study.Flow cytometric analysis of leukemic cells from AML patients revealed the surface expression of NKG2D ligands on the blasts.The median expression rates were as follows:1.72%for MICA/MICB,1.24%for ULBP-1,1.26%for ULBP-3,9.68%for ULBP-4,and 0.60%for ULBP-2/5/6.No statistically significant differences were observed in the median expression rates of NKG2D ligands between RR-AML and newly diagnosed AML patients(P>0.05).All three enrolled R/R AML patients received allogeneic CAR-NK cells at the predetermined dose post-lymphodepletion.Following infusion,CAR-NK cell expansion was detectable in all three patients.The peak level was reached 1 to 5 days after the first infusion,and the cells persisted for a maximum of 26 days.No significant coagulopathy,renal impairment,or graft-versus-host disease was observed in any of the three patients following CAR-NK cell infusion.However,one patient developed cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.In the CAR-NK treated cohort,two patients failed to respond,whereas one achieved complete remission.The responder successfully bridged to related donor haploidentical hematopoietic stem cell transplantation(HSCT),with subsequent rapid hematopoietic reconstitution and establishment of full donor chimerism.Conclusion NKG2DLs are expressed on the surface of leukemic cells in both newly diagnosed and RR-AML patients.Allogeneic umbilical cord blood-derived NKG2DL-targeting CAR-NK cells demonstrated an acceptable safety profile without new safety concerns upon infusion in RR-AML patients,although their persistence in vivo was relatively short-lived.Notably,RR-AML patients who responded to CAR-NK therapy could be successfully bridged to allogeneic HSCT.
Keywords：acute myeloid leukemiaNKG2D ligandschimeric antigen receptor natural killer cells
Publication Date：2025-11-28
Online Publishing Date：2026-01-05(First online date of this platform, not the publication date of the document)
Pages：7( 1087-1093 )