Redirected Primary Human Chimeric Antigen Receptor Natural Killer Cells As an “Off-the-Shelf Immunotherapy” for Improvement in Cancer Treatment

Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically m...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Olaf Oberschmidt [verfasserIn] Stephan Kloess [verfasserIn] Ulrike Koehl [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	natural killer cells chimeric antigen receptor chimeric antigen receptor-associated signaling domain intracellular chimeric antigen receptor-dependent signaling cancer immunotherapy

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 8(2017)
Übergeordnetes Werk:	volume:8 ; year:2017

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2017.00654

Katalog-ID:	DOAJ008528462

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spelling	10.3389/fimmu.2017.00654 doi (DE-627)DOAJ008528462 (DE-599)DOAJ100abd1ef9fa411aacd3608f303942a4 DE-627 ger DE-627 rakwb eng RC581-607 Olaf Oberschmidt verfasserin aut Redirected Primary Human Chimeric Antigen Receptor Natural Killer Cells As an “Off-the-Shelf Immunotherapy” for Improvement in Cancer Treatment 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release. This mini-review summarizes both the first preclinical trials with CAR-engineered primary human NK cells and the translational implications for “off-the-shelf immunotherapy” in cancer treatment. Signal transduction in NK cells as well as optimization of CAR signaling will be described, becoming more and more a focal point of interest in addition to redirected T cells. Finally, strategies to overcome off-target effects will be discussed in order to improve future clinical trials and to avoid attacking healthy tissues. natural killer cells chimeric antigen receptor chimeric antigen receptor-associated signaling domain intracellular chimeric antigen receptor-dependent signaling cancer immunotherapy Immunologic diseases. Allergy Stephan Kloess verfasserin aut Ulrike Koehl verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.00654 kostenfrei https://doaj.org/article/100abd1ef9fa411aacd3608f303942a4 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.00654/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017
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allfieldsGer	10.3389/fimmu.2017.00654 doi (DE-627)DOAJ008528462 (DE-599)DOAJ100abd1ef9fa411aacd3608f303942a4 DE-627 ger DE-627 rakwb eng RC581-607 Olaf Oberschmidt verfasserin aut Redirected Primary Human Chimeric Antigen Receptor Natural Killer Cells As an “Off-the-Shelf Immunotherapy” for Improvement in Cancer Treatment 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release. This mini-review summarizes both the first preclinical trials with CAR-engineered primary human NK cells and the translational implications for “off-the-shelf immunotherapy” in cancer treatment. Signal transduction in NK cells as well as optimization of CAR signaling will be described, becoming more and more a focal point of interest in addition to redirected T cells. Finally, strategies to overcome off-target effects will be discussed in order to improve future clinical trials and to avoid attacking healthy tissues. natural killer cells chimeric antigen receptor chimeric antigen receptor-associated signaling domain intracellular chimeric antigen receptor-dependent signaling cancer immunotherapy Immunologic diseases. Allergy Stephan Kloess verfasserin aut Ulrike Koehl verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.00654 kostenfrei https://doaj.org/article/100abd1ef9fa411aacd3608f303942a4 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.00654/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017
allfieldsSound	10.3389/fimmu.2017.00654 doi (DE-627)DOAJ008528462 (DE-599)DOAJ100abd1ef9fa411aacd3608f303942a4 DE-627 ger DE-627 rakwb eng RC581-607 Olaf Oberschmidt verfasserin aut Redirected Primary Human Chimeric Antigen Receptor Natural Killer Cells As an “Off-the-Shelf Immunotherapy” for Improvement in Cancer Treatment 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release. This mini-review summarizes both the first preclinical trials with CAR-engineered primary human NK cells and the translational implications for “off-the-shelf immunotherapy” in cancer treatment. Signal transduction in NK cells as well as optimization of CAR signaling will be described, becoming more and more a focal point of interest in addition to redirected T cells. Finally, strategies to overcome off-target effects will be discussed in order to improve future clinical trials and to avoid attacking healthy tissues. natural killer cells chimeric antigen receptor chimeric antigen receptor-associated signaling domain intracellular chimeric antigen receptor-dependent signaling cancer immunotherapy Immunologic diseases. Allergy Stephan Kloess verfasserin aut Ulrike Koehl verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.00654 kostenfrei https://doaj.org/article/100abd1ef9fa411aacd3608f303942a4 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.00654/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017
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callnumber-first	R - Medicine
author	Olaf Oberschmidt
spellingShingle	Olaf Oberschmidt misc RC581-607 misc natural killer cells misc chimeric antigen receptor misc chimeric antigen receptor-associated signaling domain misc intracellular chimeric antigen receptor-dependent signaling misc cancer immunotherapy misc Immunologic diseases. Allergy Redirected Primary Human Chimeric Antigen Receptor Natural Killer Cells As an “Off-the-Shelf Immunotherapy” for Improvement in Cancer Treatment
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topic_title	RC581-607 Redirected Primary Human Chimeric Antigen Receptor Natural Killer Cells As an “Off-the-Shelf Immunotherapy” for Improvement in Cancer Treatment natural killer cells chimeric antigen receptor chimeric antigen receptor-associated signaling domain intracellular chimeric antigen receptor-dependent signaling cancer immunotherapy
topic	misc RC581-607 misc natural killer cells misc chimeric antigen receptor misc chimeric antigen receptor-associated signaling domain misc intracellular chimeric antigen receptor-dependent signaling misc cancer immunotherapy misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc natural killer cells misc chimeric antigen receptor misc chimeric antigen receptor-associated signaling domain misc intracellular chimeric antigen receptor-dependent signaling misc cancer immunotherapy misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc natural killer cells misc chimeric antigen receptor misc chimeric antigen receptor-associated signaling domain misc intracellular chimeric antigen receptor-dependent signaling misc cancer immunotherapy misc Immunologic diseases. Allergy
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title	Redirected Primary Human Chimeric Antigen Receptor Natural Killer Cells As an “Off-the-Shelf Immunotherapy” for Improvement in Cancer Treatment
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title_full	Redirected Primary Human Chimeric Antigen Receptor Natural Killer Cells As an “Off-the-Shelf Immunotherapy” for Improvement in Cancer Treatment
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title_sort	redirected primary human chimeric antigen receptor natural killer cells as an “off-the-shelf immunotherapy” for improvement in cancer treatment
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title_auth	Redirected Primary Human Chimeric Antigen Receptor Natural Killer Cells As an “Off-the-Shelf Immunotherapy” for Improvement in Cancer Treatment
abstract	Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release. This mini-review summarizes both the first preclinical trials with CAR-engineered primary human NK cells and the translational implications for “off-the-shelf immunotherapy” in cancer treatment. Signal transduction in NK cells as well as optimization of CAR signaling will be described, becoming more and more a focal point of interest in addition to redirected T cells. Finally, strategies to overcome off-target effects will be discussed in order to improve future clinical trials and to avoid attacking healthy tissues.
abstractGer	Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release. This mini-review summarizes both the first preclinical trials with CAR-engineered primary human NK cells and the translational implications for “off-the-shelf immunotherapy” in cancer treatment. Signal transduction in NK cells as well as optimization of CAR signaling will be described, becoming more and more a focal point of interest in addition to redirected T cells. Finally, strategies to overcome off-target effects will be discussed in order to improve future clinical trials and to avoid attacking healthy tissues.
abstract_unstemmed	Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release. This mini-review summarizes both the first preclinical trials with CAR-engineered primary human NK cells and the translational implications for “off-the-shelf immunotherapy” in cancer treatment. Signal transduction in NK cells as well as optimization of CAR signaling will be described, becoming more and more a focal point of interest in addition to redirected T cells. Finally, strategies to overcome off-target effects will be discussed in order to improve future clinical trials and to avoid attacking healthy tissues.
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title_short	Redirected Primary Human Chimeric Antigen Receptor Natural Killer Cells As an “Off-the-Shelf Immunotherapy” for Improvement in Cancer Treatment
url	https://doi.org/10.3389/fimmu.2017.00654 https://doaj.org/article/100abd1ef9fa411aacd3608f303942a4 http://journal.frontiersin.org/article/10.3389/fimmu.2017.00654/full https://doaj.org/toc/1664-3224
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up_date	2024-07-03T18:31:50.182Z
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