Phenotype and function of human natural killer cells purified by using a clinical-scale immunomagnetic method

Department of Hematology-Oncology, St. Jude Children's Research Hospital, Mail Stop 260, 332 N. Lauderdale Street, Memphis, TN 38105, USA.
Cancer Immunology and Immunotherapy (Impact Factor: 3.94). 05/2005; 54(4):389-94. DOI: 10.1007/s00262-004-0609-6
Source: PubMed


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.

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Available from: Marti Holladay, Jul 10, 2014
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    • "However, the clinical responses of these studies have been unsatisfactory, and thus further efforts will be needed. Development of ex vivo expansion and activation of NK cells has been extensively assessed by groups at St. Jude Children's Research Hospital (Leung et al., 2005), the National Institutes of Health (Berg et al., 2009), Singapore (Suck et al., 2011), and the Karolinska Institute (Sutlu et al., 2010). These methods have generally been based on CD56-positive selection with or without CD3-depletion/CD3-suppression followed by IL-2 and/or IL-15 stimulation, and in some case virus-infected feeder cells have been used to obtain highly activated NK cells. "
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    • "A large number of NK cells can be collected from a healthy donor by a single largevolume leukapheresis process. Purified NK cells can be easily prepared using an NK cell-specific antibody, such as anti- CD56, and immunomagnetic methods (Iyengar et al, 2003; Leung et al, 2005a). The end products usually contain no measurable T cells or B cells, thus avoiding GVHD and Epstein-Barr virus-associated lymphoproliferative disease. "
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    • "Therefore, it is logical to examine the application of the receptor – ligand mismatch model to autologous HCTs. Because lymphoid leukaemias and solid tumours such as neuroblastoma are susceptible to KIR – HLA mismatched NK cell – mediated lysis (Leung et al, 2004, 2005a), we conducted a prospective study to test the hypothesis that patients with lymphoma or other solid tumour who receive autologous HCT have a low risk of relapse if KIR – HLA mismatch(es) is present. "
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