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Phenotype and function of human natural killer cells purified by using a clinical-scale immunomagnetic method
Authors:Wing Leung  Rekha Iyengar  Thasia Leimig  Marti S Holladay  James Houston  Rupert Handgretinger
Institution:(1) Department of Hematology-Oncology, St. Jude Childrenrsquos Research Hospital, Mail Stop 260, 332 N. Lauderdale Street, Memphis, TN 38105, USA;(2) Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, USA
Abstract:Infection, disease relapse, graft failure, and graft-versus-host disease (GVHD) are significant adverse events associated with allogeneic bone marrow transplantation. Donor natural killer (NK) cells may be an ideal cell type for prevention or treatment of all these adverse events. Therefore, we investigated the phenotype and function of human NK cells purified by using a clinical-scale immunomagnetic method. We found that the NK cell purification procedures did not adversely affect the expression of killer cell immunoglobulin-like receptors, adhesion molecules, intracellular cytokines, perforin, and granzyme B. Purified NK cells had extensive proliferative capacity and potent antitumor activity when assessed using an immunodeficient mouse model. While all mice transplanted with unpurified mononuclear cells developed GVHD, none of the mice transplanted with purified NK cells did. NK cells were highly susceptible to lysis by antithymocyte globulin (ATG), whereas G-CSF had a minimal effect on their natural cytotoxicity. These results support future clinical investigation of the use of purified NK cells for adoptive immunotherapy in the absence of ATG.
Keywords:Adoptive immunotherapy  Antithymocyte globulin  Bone marrow transplantation  Leukemia  Natural killer cell  Neuroblastoma
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