In some patients treated with allogeneic-HSCT, PB-NK cell alloreactivity as determined by missing KIR ligands appears to predict reduced rates of relapse and graft versus host disease (GVHD). However the precise role of KIR-ligand mismatch in HSCT is not known.
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This forms the basis for the “missing self” hypothesis and is thought to mediate donor NK cell alloreactivity in the setting of allogeneic HSCT. Specifically, NK cells are cytotoxic to cells lacking appropriate self-major histocompatibility complex (MHC) class I molecules via disinhibition of the killer immunoglobulin-like receptor (KIR). NK cell cytotoxic activity can be triggered by cytokines, antibodies or a shift in the balance between their activating and inhibitory receptors.
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In addition, a relative decrease in NK cell frequency or function in MM patients has been shown to correlate with more advanced disease or poorer outcome. NK cells have been shown to be active against MM in several preclinical studies. Natural killer (NK) cells are CD56 +/CD3 − cytotoxic lymphocytes that are increasingly recognized as a potent cellular therapy. It is currently considered incurable, even after high dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). Multiple myeloma (MM) is the second most common hematologic malignancy in adults. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported by the National Institutes of Health K12 CA088084 (Shah) and Cancer Prevention and Research Institute of Texas RP#100430 (Shpall).
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Received: ApAccepted: AugPublished: October 18, 2013Ĭopyright: © 2013 Shah et al. PLoS ONE 8(10):Įditor: Evren Alici, Karolinska Institutet, Sweden (2013) Antigen Presenting Cell-Mediated Expansion of Human Umbilical Cord Blood Yields Log-Scale Expansion of Natural Killer Cells with Anti-Myeloma Activity. Our findings introduce a clinically applicable strategy for the generation of highly functional CB-NK cells which can be used to eradicate MM.Ĭitation: Shah N, Martin-Antonio B, Yang H, Ku S, Lee DA, Cooper LJN, et al.
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Finally, aAPC-expanded CB-NK cells showed significant in vivo activity against MM in a xenogenic mouse model. Furthermore, CB-NK cells formed functional immune synapses with and demonstrated cytotoxicity against various MM targets. Though surface expression of some cytotoxicity receptors was decreased, aAPC-expanded CB-NK cells exhibited a phenotype similar to CB-NK cells expanded with IL-2 alone with respect to various inhibitory receptors, NKG2C and CD94 and maintained strong expression of transcription factors Eomesodermin and T-bet. After 14 days, mean fold expansion of CB-NK cells was 1848-fold from fresh and 2389-fold from cryopreserved CB with >95% purity for NK cells (CD56 +/CD3 −) and less than 1% CD3 + cells. Here we describe a novel strategy for expanding NK cells from cryopreserved CB units using artificial antigen presenting feeder cells (aAPC) in a gas permeable culture system. Umbilical cord blood (CB) is a promising source of allogeneic NK cells but large scale ex vivo expansion is required for generation of clinically relevant CB-derived NK (CB-NK) cell doses. Natural killer (NK) cells are important mediators of anti-tumor immunity and are active against several hematologic malignancies, including multiple myeloma (MM).