Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells

Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are pre...
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Autor*in:	Nicole Cordes [verfasserIn] Carolin Kolbe [verfasserIn] Dominik Lock [verfasserIn] Tatjana Holzer [verfasserIn] Deborah Althoff [verfasserIn] Daniel Schäfer [verfasserIn] Franziska Blaeschke [verfasserIn] Bettina Kotter [verfasserIn] Sandra Karitzky [verfasserIn] Claudia Rossig [verfasserIn] Toni Cathomen [verfasserIn] Tobias Feuchtinger [verfasserIn] Iris Bürger [verfasserIn] Mario Assenmacher [verfasserIn] Thomas Schaser [verfasserIn] Andrew D. Kaiser [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	CAR-T CAR-B immunotherapy lentiviral vector CAR display CAR-T cell resistance

Übergeordnetes Werk:	In: Molecular Therapy: Methods & Clinical Development - Elsevier, 2015, 21(2021), Seite 42-53
Übergeordnetes Werk:	volume:21 ; year:2021 ; pages:42-53

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.omtm.2021.02.013

Katalog-ID:	DOAJ076039358

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520			\|a Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. This suggests that LVs bind via displayed CAR molecules to CAR antigen-expressing cells. The relevance for CAR-T cell manufacturing was evaluated when PBMCs and B-ALL malignant B cells were mixed and transduced with anti-CD19 or anti-CD20 CAR-displaying LVs in clinically relevant doses to mimic transduction conditions of unpurified patient leukapheresis samples. Malignant B cells were transduced at higher levels with LVs displaying anti-CD19 CARs compared to LVs displaying non-binding control constructs. Stability of gene transfer was confirmed by applying a potent LV inhibitor and long-term cultures for 10 days. Our findings provide a potential explanation for the emergence of CAR-B cells pointing to safer manufacturing procedures with reduced risk of this rare type of relapse in the future.
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700	0		\|a Mario Assenmacher \|e verfasserin \|4 aut
700	0		\|a Thomas Schaser \|e verfasserin \|4 aut
700	0		\|a Andrew D. Kaiser \|e verfasserin \|4 aut
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matchkey_str	article:23290501:2021----::nid9asipaeateufcolniiavcoprilsrmttasu
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allfields	10.1016/j.omtm.2021.02.013 doi (DE-627)DOAJ076039358 (DE-599)DOAJc35a2ae8e0aa4f12be416e571f892b51 DE-627 ger DE-627 rakwb eng QH426-470 QH573-671 Nicole Cordes verfasserin aut Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. This suggests that LVs bind via displayed CAR molecules to CAR antigen-expressing cells. The relevance for CAR-T cell manufacturing was evaluated when PBMCs and B-ALL malignant B cells were mixed and transduced with anti-CD19 or anti-CD20 CAR-displaying LVs in clinically relevant doses to mimic transduction conditions of unpurified patient leukapheresis samples. Malignant B cells were transduced at higher levels with LVs displaying anti-CD19 CARs compared to LVs displaying non-binding control constructs. Stability of gene transfer was confirmed by applying a potent LV inhibitor and long-term cultures for 10 days. Our findings provide a potential explanation for the emergence of CAR-B cells pointing to safer manufacturing procedures with reduced risk of this rare type of relapse in the future. CAR-T CAR-B immunotherapy lentiviral vector CAR display CAR-T cell resistance Genetics Cytology Carolin Kolbe verfasserin aut Dominik Lock verfasserin aut Tatjana Holzer verfasserin aut Deborah Althoff verfasserin aut Daniel Schäfer verfasserin aut Franziska Blaeschke verfasserin aut Bettina Kotter verfasserin aut Sandra Karitzky verfasserin aut Claudia Rossig verfasserin aut Toni Cathomen verfasserin aut Tobias Feuchtinger verfasserin aut Iris Bürger verfasserin aut Mario Assenmacher verfasserin aut Thomas Schaser verfasserin aut Andrew D. Kaiser verfasserin aut In Molecular Therapy: Methods & Clinical Development Elsevier, 2015 21(2021), Seite 42-53 (DE-627)863823203 (DE-600)2863173-0 23290501 nnns volume:21 year:2021 pages:42-53 https://doi.org/10.1016/j.omtm.2021.02.013 kostenfrei https://doaj.org/article/c35a2ae8e0aa4f12be416e571f892b51 kostenfrei http://www.sciencedirect.com/science/article/pii/S2329050121000280 kostenfrei https://doaj.org/toc/2329-0501 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 21 2021 42-53
spelling	10.1016/j.omtm.2021.02.013 doi (DE-627)DOAJ076039358 (DE-599)DOAJc35a2ae8e0aa4f12be416e571f892b51 DE-627 ger DE-627 rakwb eng QH426-470 QH573-671 Nicole Cordes verfasserin aut Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. This suggests that LVs bind via displayed CAR molecules to CAR antigen-expressing cells. The relevance for CAR-T cell manufacturing was evaluated when PBMCs and B-ALL malignant B cells were mixed and transduced with anti-CD19 or anti-CD20 CAR-displaying LVs in clinically relevant doses to mimic transduction conditions of unpurified patient leukapheresis samples. Malignant B cells were transduced at higher levels with LVs displaying anti-CD19 CARs compared to LVs displaying non-binding control constructs. Stability of gene transfer was confirmed by applying a potent LV inhibitor and long-term cultures for 10 days. Our findings provide a potential explanation for the emergence of CAR-B cells pointing to safer manufacturing procedures with reduced risk of this rare type of relapse in the future. CAR-T CAR-B immunotherapy lentiviral vector CAR display CAR-T cell resistance Genetics Cytology Carolin Kolbe verfasserin aut Dominik Lock verfasserin aut Tatjana Holzer verfasserin aut Deborah Althoff verfasserin aut Daniel Schäfer verfasserin aut Franziska Blaeschke verfasserin aut Bettina Kotter verfasserin aut Sandra Karitzky verfasserin aut Claudia Rossig verfasserin aut Toni Cathomen verfasserin aut Tobias Feuchtinger verfasserin aut Iris Bürger verfasserin aut Mario Assenmacher verfasserin aut Thomas Schaser verfasserin aut Andrew D. Kaiser verfasserin aut In Molecular Therapy: Methods & Clinical Development Elsevier, 2015 21(2021), Seite 42-53 (DE-627)863823203 (DE-600)2863173-0 23290501 nnns volume:21 year:2021 pages:42-53 https://doi.org/10.1016/j.omtm.2021.02.013 kostenfrei https://doaj.org/article/c35a2ae8e0aa4f12be416e571f892b51 kostenfrei http://www.sciencedirect.com/science/article/pii/S2329050121000280 kostenfrei https://doaj.org/toc/2329-0501 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 21 2021 42-53
allfields_unstemmed	10.1016/j.omtm.2021.02.013 doi (DE-627)DOAJ076039358 (DE-599)DOAJc35a2ae8e0aa4f12be416e571f892b51 DE-627 ger DE-627 rakwb eng QH426-470 QH573-671 Nicole Cordes verfasserin aut Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. This suggests that LVs bind via displayed CAR molecules to CAR antigen-expressing cells. The relevance for CAR-T cell manufacturing was evaluated when PBMCs and B-ALL malignant B cells were mixed and transduced with anti-CD19 or anti-CD20 CAR-displaying LVs in clinically relevant doses to mimic transduction conditions of unpurified patient leukapheresis samples. Malignant B cells were transduced at higher levels with LVs displaying anti-CD19 CARs compared to LVs displaying non-binding control constructs. Stability of gene transfer was confirmed by applying a potent LV inhibitor and long-term cultures for 10 days. Our findings provide a potential explanation for the emergence of CAR-B cells pointing to safer manufacturing procedures with reduced risk of this rare type of relapse in the future. CAR-T CAR-B immunotherapy lentiviral vector CAR display CAR-T cell resistance Genetics Cytology Carolin Kolbe verfasserin aut Dominik Lock verfasserin aut Tatjana Holzer verfasserin aut Deborah Althoff verfasserin aut Daniel Schäfer verfasserin aut Franziska Blaeschke verfasserin aut Bettina Kotter verfasserin aut Sandra Karitzky verfasserin aut Claudia Rossig verfasserin aut Toni Cathomen verfasserin aut Tobias Feuchtinger verfasserin aut Iris Bürger verfasserin aut Mario Assenmacher verfasserin aut Thomas Schaser verfasserin aut Andrew D. Kaiser verfasserin aut In Molecular Therapy: Methods & Clinical Development Elsevier, 2015 21(2021), Seite 42-53 (DE-627)863823203 (DE-600)2863173-0 23290501 nnns volume:21 year:2021 pages:42-53 https://doi.org/10.1016/j.omtm.2021.02.013 kostenfrei https://doaj.org/article/c35a2ae8e0aa4f12be416e571f892b51 kostenfrei http://www.sciencedirect.com/science/article/pii/S2329050121000280 kostenfrei https://doaj.org/toc/2329-0501 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 21 2021 42-53
allfieldsGer	10.1016/j.omtm.2021.02.013 doi (DE-627)DOAJ076039358 (DE-599)DOAJc35a2ae8e0aa4f12be416e571f892b51 DE-627 ger DE-627 rakwb eng QH426-470 QH573-671 Nicole Cordes verfasserin aut Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. This suggests that LVs bind via displayed CAR molecules to CAR antigen-expressing cells. The relevance for CAR-T cell manufacturing was evaluated when PBMCs and B-ALL malignant B cells were mixed and transduced with anti-CD19 or anti-CD20 CAR-displaying LVs in clinically relevant doses to mimic transduction conditions of unpurified patient leukapheresis samples. Malignant B cells were transduced at higher levels with LVs displaying anti-CD19 CARs compared to LVs displaying non-binding control constructs. Stability of gene transfer was confirmed by applying a potent LV inhibitor and long-term cultures for 10 days. Our findings provide a potential explanation for the emergence of CAR-B cells pointing to safer manufacturing procedures with reduced risk of this rare type of relapse in the future. CAR-T CAR-B immunotherapy lentiviral vector CAR display CAR-T cell resistance Genetics Cytology Carolin Kolbe verfasserin aut Dominik Lock verfasserin aut Tatjana Holzer verfasserin aut Deborah Althoff verfasserin aut Daniel Schäfer verfasserin aut Franziska Blaeschke verfasserin aut Bettina Kotter verfasserin aut Sandra Karitzky verfasserin aut Claudia Rossig verfasserin aut Toni Cathomen verfasserin aut Tobias Feuchtinger verfasserin aut Iris Bürger verfasserin aut Mario Assenmacher verfasserin aut Thomas Schaser verfasserin aut Andrew D. Kaiser verfasserin aut In Molecular Therapy: Methods & Clinical Development Elsevier, 2015 21(2021), Seite 42-53 (DE-627)863823203 (DE-600)2863173-0 23290501 nnns volume:21 year:2021 pages:42-53 https://doi.org/10.1016/j.omtm.2021.02.013 kostenfrei https://doaj.org/article/c35a2ae8e0aa4f12be416e571f892b51 kostenfrei http://www.sciencedirect.com/science/article/pii/S2329050121000280 kostenfrei https://doaj.org/toc/2329-0501 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 21 2021 42-53
allfieldsSound	10.1016/j.omtm.2021.02.013 doi (DE-627)DOAJ076039358 (DE-599)DOAJc35a2ae8e0aa4f12be416e571f892b51 DE-627 ger DE-627 rakwb eng QH426-470 QH573-671 Nicole Cordes verfasserin aut Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. This suggests that LVs bind via displayed CAR molecules to CAR antigen-expressing cells. The relevance for CAR-T cell manufacturing was evaluated when PBMCs and B-ALL malignant B cells were mixed and transduced with anti-CD19 or anti-CD20 CAR-displaying LVs in clinically relevant doses to mimic transduction conditions of unpurified patient leukapheresis samples. Malignant B cells were transduced at higher levels with LVs displaying anti-CD19 CARs compared to LVs displaying non-binding control constructs. Stability of gene transfer was confirmed by applying a potent LV inhibitor and long-term cultures for 10 days. Our findings provide a potential explanation for the emergence of CAR-B cells pointing to safer manufacturing procedures with reduced risk of this rare type of relapse in the future. CAR-T CAR-B immunotherapy lentiviral vector CAR display CAR-T cell resistance Genetics Cytology Carolin Kolbe verfasserin aut Dominik Lock verfasserin aut Tatjana Holzer verfasserin aut Deborah Althoff verfasserin aut Daniel Schäfer verfasserin aut Franziska Blaeschke verfasserin aut Bettina Kotter verfasserin aut Sandra Karitzky verfasserin aut Claudia Rossig verfasserin aut Toni Cathomen verfasserin aut Tobias Feuchtinger verfasserin aut Iris Bürger verfasserin aut Mario Assenmacher verfasserin aut Thomas Schaser verfasserin aut Andrew D. Kaiser verfasserin aut In Molecular Therapy: Methods & Clinical Development Elsevier, 2015 21(2021), Seite 42-53 (DE-627)863823203 (DE-600)2863173-0 23290501 nnns volume:21 year:2021 pages:42-53 https://doi.org/10.1016/j.omtm.2021.02.013 kostenfrei https://doaj.org/article/c35a2ae8e0aa4f12be416e571f892b51 kostenfrei http://www.sciencedirect.com/science/article/pii/S2329050121000280 kostenfrei https://doaj.org/toc/2329-0501 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 21 2021 42-53
language	English
source	In Molecular Therapy: Methods & Clinical Development 21(2021), Seite 42-53 volume:21 year:2021 pages:42-53
sourceStr	In Molecular Therapy: Methods & Clinical Development 21(2021), Seite 42-53 volume:21 year:2021 pages:42-53
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	CAR-T CAR-B immunotherapy lentiviral vector CAR display CAR-T cell resistance Genetics Cytology
isfreeaccess_bool	true
container_title	Molecular Therapy: Methods & Clinical Development
authorswithroles_txt_mv	Nicole Cordes @@aut@@ Carolin Kolbe @@aut@@ Dominik Lock @@aut@@ Tatjana Holzer @@aut@@ Deborah Althoff @@aut@@ Daniel Schäfer @@aut@@ Franziska Blaeschke @@aut@@ Bettina Kotter @@aut@@ Sandra Karitzky @@aut@@ Claudia Rossig @@aut@@ Toni Cathomen @@aut@@ Tobias Feuchtinger @@aut@@ Iris Bürger @@aut@@ Mario Assenmacher @@aut@@ Thomas Schaser @@aut@@ Andrew D. Kaiser @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	863823203
id	DOAJ076039358
language_de	englisch
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callnumber-first	Q - Science
author	Nicole Cordes
spellingShingle	Nicole Cordes misc QH426-470 misc QH573-671 misc CAR-T misc CAR-B misc immunotherapy misc lentiviral vector misc CAR display misc CAR-T cell resistance misc Genetics misc Cytology Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells
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topic_title	QH426-470 QH573-671 Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells CAR-T CAR-B immunotherapy lentiviral vector CAR display CAR-T cell resistance
topic	misc QH426-470 misc QH573-671 misc CAR-T misc CAR-B misc immunotherapy misc lentiviral vector misc CAR display misc CAR-T cell resistance misc Genetics misc Cytology
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title	Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells
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title_full	Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells
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author_browse	Nicole Cordes Carolin Kolbe Dominik Lock Tatjana Holzer Deborah Althoff Daniel Schäfer Franziska Blaeschke Bettina Kotter Sandra Karitzky Claudia Rossig Toni Cathomen Tobias Feuchtinger Iris Bürger Mario Assenmacher Thomas Schaser Andrew D. Kaiser
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title_sort	anti-cd19 cars displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells
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title_auth	Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells
abstract	Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. This suggests that LVs bind via displayed CAR molecules to CAR antigen-expressing cells. The relevance for CAR-T cell manufacturing was evaluated when PBMCs and B-ALL malignant B cells were mixed and transduced with anti-CD19 or anti-CD20 CAR-displaying LVs in clinically relevant doses to mimic transduction conditions of unpurified patient leukapheresis samples. Malignant B cells were transduced at higher levels with LVs displaying anti-CD19 CARs compared to LVs displaying non-binding control constructs. Stability of gene transfer was confirmed by applying a potent LV inhibitor and long-term cultures for 10 days. Our findings provide a potential explanation for the emergence of CAR-B cells pointing to safer manufacturing procedures with reduced risk of this rare type of relapse in the future.
abstractGer	Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. This suggests that LVs bind via displayed CAR molecules to CAR antigen-expressing cells. The relevance for CAR-T cell manufacturing was evaluated when PBMCs and B-ALL malignant B cells were mixed and transduced with anti-CD19 or anti-CD20 CAR-displaying LVs in clinically relevant doses to mimic transduction conditions of unpurified patient leukapheresis samples. Malignant B cells were transduced at higher levels with LVs displaying anti-CD19 CARs compared to LVs displaying non-binding control constructs. Stability of gene transfer was confirmed by applying a potent LV inhibitor and long-term cultures for 10 days. Our findings provide a potential explanation for the emergence of CAR-B cells pointing to safer manufacturing procedures with reduced risk of this rare type of relapse in the future.
abstract_unstemmed	Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. This suggests that LVs bind via displayed CAR molecules to CAR antigen-expressing cells. The relevance for CAR-T cell manufacturing was evaluated when PBMCs and B-ALL malignant B cells were mixed and transduced with anti-CD19 or anti-CD20 CAR-displaying LVs in clinically relevant doses to mimic transduction conditions of unpurified patient leukapheresis samples. Malignant B cells were transduced at higher levels with LVs displaying anti-CD19 CARs compared to LVs displaying non-binding control constructs. Stability of gene transfer was confirmed by applying a potent LV inhibitor and long-term cultures for 10 days. Our findings provide a potential explanation for the emergence of CAR-B cells pointing to safer manufacturing procedures with reduced risk of this rare type of relapse in the future.
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title_short	Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells
url	https://doi.org/10.1016/j.omtm.2021.02.013 https://doaj.org/article/c35a2ae8e0aa4f12be416e571f892b51 http://www.sciencedirect.com/science/article/pii/S2329050121000280 https://doaj.org/toc/2329-0501
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up_date	2024-07-03T18:15:43.180Z
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Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells

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