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Genetic Manipulation of NK Cells for Cancer Immunotherapy: Techniques and Clinical Implications

Given their rapid and efficient capacity to recognize and kill tumor cells, natural killer (NK) cells represent a unique immune cell to genetically reprogram in an effort to improve the outcome of cell-based cancer immunotherapy. However, technical and biological challenges associated with gene deli...

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Autores principales: Carlsten, Mattias, Childs, Richard W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462109/
https://www.ncbi.nlm.nih.gov/pubmed/26113846
http://dx.doi.org/10.3389/fimmu.2015.00266
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author Carlsten, Mattias
Childs, Richard W.
author_facet Carlsten, Mattias
Childs, Richard W.
author_sort Carlsten, Mattias
collection PubMed
description Given their rapid and efficient capacity to recognize and kill tumor cells, natural killer (NK) cells represent a unique immune cell to genetically reprogram in an effort to improve the outcome of cell-based cancer immunotherapy. However, technical and biological challenges associated with gene delivery into NK cells have significantly tempered this approach. Recent advances in viral transduction and electroporation have now allowed detailed characterization of genetically modified NK cells and provided a better understanding for how these cells can be utilized in the clinic to optimize their capacity to induce tumor regression in vivo. Improving NK cell persistence in vivo via autocrine IL-2 and IL-15 stimulation, enhancing tumor targeting by silencing inhibitory NK cell receptors such as NKG2A, and redirecting tumor killing via chimeric antigen receptors, all represent approaches that hold promise in preclinical studies. This review focuses on available methods for genetic reprograming of NK cells and the advantages and challenges associated with each method. It also gives an overview of strategies for genetic reprograming of NK cells that have been evaluated to date and an outlook on how these strategies may be best utilized in clinical protocols. With the recent advances in our understanding of the complex biological networks that regulate the ability of NK cells to target and kill tumors in vivo, we foresee genetic engineering as an obligatory pathway required to exploit the full potential of NK-cell based immunotherapy in the clinic.
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spelling pubmed-44621092015-06-25 Genetic Manipulation of NK Cells for Cancer Immunotherapy: Techniques and Clinical Implications Carlsten, Mattias Childs, Richard W. Front Immunol Immunology Given their rapid and efficient capacity to recognize and kill tumor cells, natural killer (NK) cells represent a unique immune cell to genetically reprogram in an effort to improve the outcome of cell-based cancer immunotherapy. However, technical and biological challenges associated with gene delivery into NK cells have significantly tempered this approach. Recent advances in viral transduction and electroporation have now allowed detailed characterization of genetically modified NK cells and provided a better understanding for how these cells can be utilized in the clinic to optimize their capacity to induce tumor regression in vivo. Improving NK cell persistence in vivo via autocrine IL-2 and IL-15 stimulation, enhancing tumor targeting by silencing inhibitory NK cell receptors such as NKG2A, and redirecting tumor killing via chimeric antigen receptors, all represent approaches that hold promise in preclinical studies. This review focuses on available methods for genetic reprograming of NK cells and the advantages and challenges associated with each method. It also gives an overview of strategies for genetic reprograming of NK cells that have been evaluated to date and an outlook on how these strategies may be best utilized in clinical protocols. With the recent advances in our understanding of the complex biological networks that regulate the ability of NK cells to target and kill tumors in vivo, we foresee genetic engineering as an obligatory pathway required to exploit the full potential of NK-cell based immunotherapy in the clinic. Frontiers Media S.A. 2015-06-10 /pmc/articles/PMC4462109/ /pubmed/26113846 http://dx.doi.org/10.3389/fimmu.2015.00266 Text en Copyright © 2015 Carlsten and Childs. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Carlsten, Mattias
Childs, Richard W.
Genetic Manipulation of NK Cells for Cancer Immunotherapy: Techniques and Clinical Implications
title Genetic Manipulation of NK Cells for Cancer Immunotherapy: Techniques and Clinical Implications
title_full Genetic Manipulation of NK Cells for Cancer Immunotherapy: Techniques and Clinical Implications
title_fullStr Genetic Manipulation of NK Cells for Cancer Immunotherapy: Techniques and Clinical Implications
title_full_unstemmed Genetic Manipulation of NK Cells for Cancer Immunotherapy: Techniques and Clinical Implications
title_short Genetic Manipulation of NK Cells for Cancer Immunotherapy: Techniques and Clinical Implications
title_sort genetic manipulation of nk cells for cancer immunotherapy: techniques and clinical implications
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462109/
https://www.ncbi.nlm.nih.gov/pubmed/26113846
http://dx.doi.org/10.3389/fimmu.2015.00266
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