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.
Bone Marrow Transplantation (2002) 29, 497–502. doi:10.1038/sj.bmt.1703406
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Acknowledgements
We thank Shangara Lal for critical reviewing of the manuscript and Ulrike Krauter for excellent technical assistance. This work was supported by a grant from the German Jose Carreras Leukemia Foundation and from the Deutsche Forschungs-Gesellschaft (SFB 510).
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Lang, P., Pfeiffer, M., Handgretinger, R. et al. Clinical scale isolation of T cell-depleted CD56+ donor lymphocytes in children. Bone Marrow Transplant 29, 497–502 (2002). https://doi.org/10.1038/sj.bmt.1703406
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DOI: https://doi.org/10.1038/sj.bmt.1703406
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