Generation of donor natural killer cells from CD34(+) progenitor cells and subsequent infusion after HLA-mismatched allogeneic hematopoietic cell transplantation: a feasibility study.
Post transplant infusion of donor-type natural killer (NK) cells has been shown to have an anti-leukemia-enhancing effect without evoking GVHD in murine hematopoietic cell transplantation (HCT) models. Here, we tested 14 patients (age, 23-65 years), 12 with acute leukemia and 2 with myelodysplastic syndrome, who underwent HLA-mismatched HCT and subsequently received donor NK cell infusions. Cell donors (age, 16-51 years), comprising seven siblings, five offspring, and two mothers of the patients, underwent growth factor-mobilized leukapheresis for 3-5 days. Cells collected on the first 2-4 days were used for HCT, whereas those collected on the last day were CD34 selected by magnetic-activated cell sorting (median, 2.22 x 10(6) cells/kg; range, 0.29-5.66). Donor NK cells were generated from the CD34(+) cells by ex vivo cell culture over a 6-week period (median, 9.28 x 10(6) cells/kg; range, 0.33-24.50; CD122/CD56(+) 64%; CD3(+) 1.0%; and viability 88%). There were no signs of acute toxicity in patients infused with these cells 6-7 weeks post transplant. Overall, one and five patients developed acute and chronic GVHD during post transplant period, respectively. These results showed that clinical-grade donor NK cell production from CD34(+) cells is feasible.
Yoon
S R
SR
Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Lee
Y S
YS
Yang
S H
SH
Ahn
K H
KH
Lee
Je-H
JH
Lee
Ju-H
JH
Kim
D Y
DY
Kang
Y A
YA
Jeon
M
M
Seol
M
M
Ryu
S G
SG
Chung
J W
JW
Choi
I
I
Lee
K H
KH
D000328:Adult; D018952:Antigens, CD34; D018929:Cell Culture Techniques; D005240:Feasibility Studies; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000637:transplantation*; D007938:Leukemia / Q000628:therapy; D017710:Lymphocyte Transfusion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
D018952:Antigens, CD34; D006680:HLA Antigens