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Pluripotent stem cell-derived natural killer cells for cancer therapy

Published:August 05, 2010DOI:https://doi.org/10.1016/j.trsl.2010.07.008
      Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) provide an accessible, genetically tractable, and homogenous starting cell population to efficiently study human blood cell development. These cell populations provide platforms to develop new cell-based therapies to treat both malignant and nonmalignant hematological diseases. Our group previously demonstrated the ability of hESC-derived hematopoietic precursors to produce functional natural killer (NK) cells as well as an explanation of the underlying mechanism responsible for the inefficient development of T and B cells from hESCs. hESCs and iPSCs, which can be engineered reliably in vitro, provide an important new model system to study human lymphocyte development and produce enhanced cell-based therapies with the potential to serve as a “universal” source of antitumor lymphocytes. This review will focus on the application of hESC-derived NK cells with currently used and novel therapeutics for clinical trials, barriers to translation, and future applications through genetic engineering approaches.

      Abbreviations:

      ADCC (antibody dependent cellular cytotoxicity), AML (acute myelogenous leukemia), CAR (chimeric antigen receptor), EB (embryoid body), GVHD (graft-versus-host disease), HESC (human embryonic stem cell), HIV (human immunodeficiency virus), HLA (human leukocyte antigen), HSC (hematopoietic stem cell), IFN (interferon), IL-2 (interleukin-2), iPSC (induced pluripotent stem cell), mAb (monoclonal antibody), MHC (major histocompatibility), NK (natural killer), OP9-DL1 (OP9 stroma expressing Delta-like 1), PB=NK (peripheral blood NK), TCR (T-cell receptor), TIL (tumor infiltrating lymphocyte), Treg (T regulatory), UCB (umbilical cord blood)
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