Journal
BONE MARROW TRANSPLANTATION
Volume 29, Issue 6, Pages 497-502Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bmt.1703406
Keywords
NK cells; CD56(+); isolation; immunomagnetic separation; DLI; mismatched transplantation
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We present a clinical scale method for immunomagnetic separation of CD56(+) donor natural killer cells for adoptive immunotherapy of pediatric leukemias after allogeneic transplantation. This time-saving and partially automated procedure employed CD56(+) selection followed by CD3(+) depletion, resulting in a median purity of 98.6% NK cells and a four-log depletion of T cells. The enriched NK cells demonstrated high cytotoxic activity against K562 target cells and fresh leukemic blasts with low HLA class I expression, which could be further enhanced by IL-2 stimulation. Lysis of NK-insensitive leukemic cells with high HLA class I expression could also be demonstrated via ADCC. Due to the high degree of T cell depletion, alloreactive proliferation in mixed lymphocyte cultures and response to T cell-specific mitogen stimulation was profoundly decreased. Our results suggest that, even in the case of mismatched donors, infusions of donor NK cells with extremely low T cell content may be a promising treatment option for leukemic minimal residual disease after allogeneic transplantation without risk of inducing severe GVHD.
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