Clinical scale isolation of T cell-depleted CD56+ donor lymphocytes in children |
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Authors: | Lang P Pfeiffer M Handgretinger R Schumm M Demirdelen B Stanojevic S Klingebiel Th Köhl U Kuci S Niethammer D |
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Institution: | Children's University Hospital, University of Tuebingen, Hoppe-Seyler Strasse 1, 72076 Tuebingen, Germany. |
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Abstract: | 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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