Engineering NK Cells for CAR Therapy—Recent Advances in Gene Transfer Methodology

The development of chimeric antigen receptor (CAR) T cell therapy has introduced a new and effective strategy to guide and promote the immune response against tumors in the clinic. More recently, in an attempt to enhance its utility, this method has been expanded to novel cell types. One of the more...

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Main Authors: Paula Schmidt, Martin J. Raftery, Gabriele Pecher
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2020.611163/full
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author Paula Schmidt
Martin J. Raftery
Gabriele Pecher
author_facet Paula Schmidt
Martin J. Raftery
Gabriele Pecher
author_sort Paula Schmidt
collection DOAJ
description The development of chimeric antigen receptor (CAR) T cell therapy has introduced a new and effective strategy to guide and promote the immune response against tumors in the clinic. More recently, in an attempt to enhance its utility, this method has been expanded to novel cell types. One of the more successful variants has proven to be the expression of CARs in Natural Killer (NK) cells (CAR-NK). Gene engineering NK cells to express an exogenous CAR receptor allows the innate anti-tumor ability of NK cells to be harnessed and directed against a target tumor antigen. In addition, the biology of NK cells allows the development of an allogeneic cell therapeutic product useable with most or all patient haplotypes. NK cells cause little or no graft versus host disease (GvHD) and are therefore suitable for development of an “off the shelf” therapeutic product. Initial trials have also shown that CAR-NK cells rarely cause cytokine release syndrome. However, despite their potential NK cells have proven to be difficult to engineer, with high sensitivity to apoptosis and low levels of gene expression. The creation of optimized methods to introduce genes into NK cells will promote the widespread application of CAR-NK in research laboratories and the clinics.
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spelling doaj.art-0237338cfa97420cbecce8290fa84f0d2022-12-21T22:00:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-01-011110.3389/fimmu.2020.611163611163Engineering NK Cells for CAR Therapy—Recent Advances in Gene Transfer MethodologyPaula SchmidtMartin J. RafteryGabriele PecherThe development of chimeric antigen receptor (CAR) T cell therapy has introduced a new and effective strategy to guide and promote the immune response against tumors in the clinic. More recently, in an attempt to enhance its utility, this method has been expanded to novel cell types. One of the more successful variants has proven to be the expression of CARs in Natural Killer (NK) cells (CAR-NK). Gene engineering NK cells to express an exogenous CAR receptor allows the innate anti-tumor ability of NK cells to be harnessed and directed against a target tumor antigen. In addition, the biology of NK cells allows the development of an allogeneic cell therapeutic product useable with most or all patient haplotypes. NK cells cause little or no graft versus host disease (GvHD) and are therefore suitable for development of an “off the shelf” therapeutic product. Initial trials have also shown that CAR-NK cells rarely cause cytokine release syndrome. However, despite their potential NK cells have proven to be difficult to engineer, with high sensitivity to apoptosis and low levels of gene expression. The creation of optimized methods to introduce genes into NK cells will promote the widespread application of CAR-NK in research laboratories and the clinics.https://www.frontiersin.org/articles/10.3389/fimmu.2020.611163/fullnatural killer cellschimeric antigen receptorgene engineeringtransduceelectroporation
spellingShingle Paula Schmidt
Martin J. Raftery
Gabriele Pecher
Engineering NK Cells for CAR Therapy—Recent Advances in Gene Transfer Methodology
Frontiers in Immunology
natural killer cells
chimeric antigen receptor
gene engineering
transduce
electroporation
title Engineering NK Cells for CAR Therapy—Recent Advances in Gene Transfer Methodology
title_full Engineering NK Cells for CAR Therapy—Recent Advances in Gene Transfer Methodology
title_fullStr Engineering NK Cells for CAR Therapy—Recent Advances in Gene Transfer Methodology
title_full_unstemmed Engineering NK Cells for CAR Therapy—Recent Advances in Gene Transfer Methodology
title_short Engineering NK Cells for CAR Therapy—Recent Advances in Gene Transfer Methodology
title_sort engineering nk cells for car therapy recent advances in gene transfer methodology
topic natural killer cells
chimeric antigen receptor
gene engineering
transduce
electroporation
url https://www.frontiersin.org/articles/10.3389/fimmu.2020.611163/full
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AT martinjraftery engineeringnkcellsforcartherapyrecentadvancesingenetransfermethodology
AT gabrielepecher engineeringnkcellsforcartherapyrecentadvancesingenetransfermethodology