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      When CAR Meets Stem Cells

      review-article
      Author(s):
      Publication date (Electronic):
      Journal: International Journal of Molecular Sciences
      Publisher: MDPI
      Keywords: pluripotent stem cell, CAR, CRISPR/Cas9

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          Abstract

          The generation of immune cells from human pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) has been of keen interest to regenerative medicine. Pluripotent stem cell-derived immune cells such as natural killer cells, macrophages, and lymphoid cells, especially T cells, can be used in immune cell therapy to treat incurable cancers. Moreover, since the advent of chimeric antigen receptor (CAR) technology, the success of CAR-T cells in the clinic has galvanized new efforts to harness the power of CAR technology to generate CAR-engineered immune cells from pluripotent stem cells. This review provides a summary of pluripotent stem cell-derived immune cells and CAR technology, together with perspectives on combining pluripotent stem-cell derived immune cells and CAR engineering to pave a new way for developing next generation immune cell therapy.

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          NK cells and cancer: you can teach innate cells new tricks.

          Maelig G Morvan, Lewis L Lanier (2016)
          Natural killer (NK) cells are the prototype innate lymphoid cells endowed with potent cytolytic function that provide host defence against microbial infection and tumours. Here, we review evidence for the role of NK cells in immune surveillance against cancer and highlight new therapeutic approaches for targeting NK cells in the treatment of cancer.
          Article 0 comments Cited 486 times – based on 0 reviews     Review now
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            Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity

            Branden Moriarity, Dan S. Kaufman, David L. Hermanson … (2018)
            Chimeric antigen receptors (CARs) significantly enhance anti-tumor activity of immune effector cells. While most studies have evaluated CAR-expression in T cells, here we evaluate different CAR constructs that improve natural killer (NK) cell-mediated killing. We identified a CAR containing the transmembrane domain of NKG2D, the 2B4 co-stimulatory domain, and the CD3ζ signaling domain to mediate strong antigen-specific NK cell signaling. NK cells derived from human iPSCs that express this CAR (NK-CAR-iPSC-NK cells) have a typical NK cell phenotype and demonstrate improved anti-tumor activity compared to T-CAR expressing iPSC-derived NK cells (T-CAR-iPSC-NK cells) and non-CAR expressing cells. Using an ovarian cancer xenograft model, NK-CAR-iPSC-NK cells significantly inhibited tumor growth and prolonged survival compared to PB-NK cells, iPSC-NK cells, or T-CAR-iPSC-NK cells. Additionally, NK-CAR-iPSC-NK cells demonstrate similar in vivo activity as T-CAR-expressing T cells, though with less toxicity. These NK-CAR-iPSC-NK cells now provide standardized, targeted “off the shelf” lymphocytes for anti-cancer immunotherapy. Natural killer (NK) cells are a key part of the immune system’s ability to mediate anti-cancer activity. Kaufman and colleagues utilize human iPSCs to produce NK cells with novel chimeric antigen receptors that specifically target cancer cells in an antigen-specific manner to improve survival in an ovarian cancer xenograft model.
            Article 0 comments Cited 387 times – based on 0 reviews     Review now
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              Stem cells: past, present, and future

              Wojciech J. Zakrzewski, Maciej Dobrzyński, Maria Szymonowicz … (2019)
              In recent years, stem cell therapy has become a very promising and advanced scientific research topic. The development of treatment methods has evoked great expectations. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. The genesis of stem cells is followed by laboratory steps of controlled stem cell culturing and derivation. Quality control and teratoma formation assays are important procedures in assessing the properties of the stem cells tested. Derivation methods and the utilization of culturing media are crucial to set proper environmental conditions for controlled differentiation. Among many types of stem tissue applications, the use of graphene scaffolds and the potential of extracellular vesicle-based therapies require attention due to their versatility. The review is summarized by challenges that stem cell therapy must overcome to be accepted worldwide. A wide variety of possibilities makes this cutting edge therapy a turning point in modern medicine, providing hope for untreatable diseases.
              Article 0 comments Cited 378 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 12 April 2019
                Publication date Collection: April 2019
                Volume: 20
                Issue: 8
                Electronic Location Identifier: 1825
                Affiliations
                School of Life Science, Handong Global University, Pohang 37554, Korea; jm.lee@ 123456handong.edu ; Tel.: +82-54-260-1292
                Article
                Publisher ID: ijms-20-01825
                DOI: 10.3390/ijms20081825
                PMC ID: 6514932
                PubMed ID: 31013813
                SO-VID: e85b40b8-302b-4e15-9339-3446503b9616
                Copyright © © 2019 by the author.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 26 March 2019
                Date accepted : 10 April 2019
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: pluripotent stem cell,car,crispr/cas9
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: pluripotent stem cell, car, crispr/cas9

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