Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells
Background Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the...
Ausführliche Beschreibung
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| Autor*in: |
Stroncek, David F. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2017 |
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| Schlagwörter: |
Chimeric antigen receptor T cells |
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| Anmerkung: |
© The Author(s) 2017 |
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| Übergeordnetes Werk: |
Enthalten in: Journal of translational medicine - London : BioMed Central, 2003, 15(2017), 1 vom: 16. März |
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| Übergeordnetes Werk: |
volume:15 ; year:2017 ; number:1 ; day:16 ; month:03 |
| Links: |
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| DOI / URN: |
10.1186/s12967-017-1160-5 |
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| Katalog-ID: |
SPR028963644 |
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| 520 | |a Background Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Methods Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products. Results When compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells. Conclusions Enrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes. | ||
| 650 | 4 | |a Chimeric antigen receptor T cells |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Cancer immunotherapy |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Cellular therapy |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a T cells |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Elutriation |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Myeloid derived suppressor cells |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Peripheral blood mononuclear cells |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Lee, Daniel W. |4 aut | |
| 700 | 1 | |a Ren, Jiaqiang |4 aut | |
| 700 | 1 | |a Sabatino, Marianna |4 aut | |
| 700 | 1 | |a Highfill, Steven |4 aut | |
| 700 | 1 | |a Khuu, Hanh |4 aut | |
| 700 | 1 | |a Shah, Nirali N. |4 aut | |
| 700 | 1 | |a Kaplan, Rosandra N. |4 aut | |
| 700 | 1 | |a Fry, Terry J. |4 aut | |
| 700 | 1 | |a Mackall, Crystal L. |4 aut | |
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10.1186/s12967-017-1160-5 doi (DE-627)SPR028963644 (SPR)s12967-017-1160-5-e DE-627 ger DE-627 rakwb eng Stroncek, David F. verfasserin (orcid)0000-0001-5867-3265 aut Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Background Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Methods Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products. Results When compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells. Conclusions Enrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes. Chimeric antigen receptor T cells (dpeaa)DE-He213 Cancer immunotherapy (dpeaa)DE-He213 Cellular therapy (dpeaa)DE-He213 T cells (dpeaa)DE-He213 Elutriation (dpeaa)DE-He213 Myeloid derived suppressor cells (dpeaa)DE-He213 Peripheral blood mononuclear cells (dpeaa)DE-He213 Lee, Daniel W. aut Ren, Jiaqiang aut Sabatino, Marianna aut Highfill, Steven aut Khuu, Hanh aut Shah, Nirali N. aut Kaplan, Rosandra N. aut Fry, Terry J. aut Mackall, Crystal L. aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 15(2017), 1 vom: 16. März (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:15 year:2017 number:1 day:16 month:03 https://dx.doi.org/10.1186/s12967-017-1160-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2017 1 16 03 |
| spelling |
10.1186/s12967-017-1160-5 doi (DE-627)SPR028963644 (SPR)s12967-017-1160-5-e DE-627 ger DE-627 rakwb eng Stroncek, David F. verfasserin (orcid)0000-0001-5867-3265 aut Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Background Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Methods Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products. Results When compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells. Conclusions Enrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes. Chimeric antigen receptor T cells (dpeaa)DE-He213 Cancer immunotherapy (dpeaa)DE-He213 Cellular therapy (dpeaa)DE-He213 T cells (dpeaa)DE-He213 Elutriation (dpeaa)DE-He213 Myeloid derived suppressor cells (dpeaa)DE-He213 Peripheral blood mononuclear cells (dpeaa)DE-He213 Lee, Daniel W. aut Ren, Jiaqiang aut Sabatino, Marianna aut Highfill, Steven aut Khuu, Hanh aut Shah, Nirali N. aut Kaplan, Rosandra N. aut Fry, Terry J. aut Mackall, Crystal L. aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 15(2017), 1 vom: 16. März (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:15 year:2017 number:1 day:16 month:03 https://dx.doi.org/10.1186/s12967-017-1160-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2017 1 16 03 |
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10.1186/s12967-017-1160-5 doi (DE-627)SPR028963644 (SPR)s12967-017-1160-5-e DE-627 ger DE-627 rakwb eng Stroncek, David F. verfasserin (orcid)0000-0001-5867-3265 aut Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Background Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Methods Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products. Results When compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells. Conclusions Enrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes. Chimeric antigen receptor T cells (dpeaa)DE-He213 Cancer immunotherapy (dpeaa)DE-He213 Cellular therapy (dpeaa)DE-He213 T cells (dpeaa)DE-He213 Elutriation (dpeaa)DE-He213 Myeloid derived suppressor cells (dpeaa)DE-He213 Peripheral blood mononuclear cells (dpeaa)DE-He213 Lee, Daniel W. aut Ren, Jiaqiang aut Sabatino, Marianna aut Highfill, Steven aut Khuu, Hanh aut Shah, Nirali N. aut Kaplan, Rosandra N. aut Fry, Terry J. aut Mackall, Crystal L. aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 15(2017), 1 vom: 16. März (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:15 year:2017 number:1 day:16 month:03 https://dx.doi.org/10.1186/s12967-017-1160-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2017 1 16 03 |
| allfieldsGer |
10.1186/s12967-017-1160-5 doi (DE-627)SPR028963644 (SPR)s12967-017-1160-5-e DE-627 ger DE-627 rakwb eng Stroncek, David F. verfasserin (orcid)0000-0001-5867-3265 aut Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Background Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Methods Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products. Results When compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells. Conclusions Enrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes. Chimeric antigen receptor T cells (dpeaa)DE-He213 Cancer immunotherapy (dpeaa)DE-He213 Cellular therapy (dpeaa)DE-He213 T cells (dpeaa)DE-He213 Elutriation (dpeaa)DE-He213 Myeloid derived suppressor cells (dpeaa)DE-He213 Peripheral blood mononuclear cells (dpeaa)DE-He213 Lee, Daniel W. aut Ren, Jiaqiang aut Sabatino, Marianna aut Highfill, Steven aut Khuu, Hanh aut Shah, Nirali N. aut Kaplan, Rosandra N. aut Fry, Terry J. aut Mackall, Crystal L. aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 15(2017), 1 vom: 16. März (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:15 year:2017 number:1 day:16 month:03 https://dx.doi.org/10.1186/s12967-017-1160-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2017 1 16 03 |
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10.1186/s12967-017-1160-5 doi (DE-627)SPR028963644 (SPR)s12967-017-1160-5-e DE-627 ger DE-627 rakwb eng Stroncek, David F. verfasserin (orcid)0000-0001-5867-3265 aut Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Background Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Methods Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products. Results When compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells. Conclusions Enrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes. Chimeric antigen receptor T cells (dpeaa)DE-He213 Cancer immunotherapy (dpeaa)DE-He213 Cellular therapy (dpeaa)DE-He213 T cells (dpeaa)DE-He213 Elutriation (dpeaa)DE-He213 Myeloid derived suppressor cells (dpeaa)DE-He213 Peripheral blood mononuclear cells (dpeaa)DE-He213 Lee, Daniel W. aut Ren, Jiaqiang aut Sabatino, Marianna aut Highfill, Steven aut Khuu, Hanh aut Shah, Nirali N. aut Kaplan, Rosandra N. aut Fry, Terry J. aut Mackall, Crystal L. aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 15(2017), 1 vom: 16. März (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:15 year:2017 number:1 day:16 month:03 https://dx.doi.org/10.1186/s12967-017-1160-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2017 1 16 03 |
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Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells |
| abstract |
Background Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Methods Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products. Results When compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells. Conclusions Enrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes. © The Author(s) 2017 |
| abstractGer |
Background Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Methods Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products. Results When compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells. Conclusions Enrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes. © The Author(s) 2017 |
| abstract_unstemmed |
Background Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Methods Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products. Results When compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells. Conclusions Enrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes. © The Author(s) 2017 |
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| title_short |
Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells |
| url |
https://dx.doi.org/10.1186/s12967-017-1160-5 |
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| author2 |
Lee, Daniel W. Ren, Jiaqiang Sabatino, Marianna Highfill, Steven Khuu, Hanh Shah, Nirali N. Kaplan, Rosandra N. Fry, Terry J. Mackall, Crystal L. |
| author2Str |
Lee, Daniel W. Ren, Jiaqiang Sabatino, Marianna Highfill, Steven Khuu, Hanh Shah, Nirali N. Kaplan, Rosandra N. Fry, Terry J. Mackall, Crystal L. |
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| doi_str |
10.1186/s12967-017-1160-5 |
| up_date |
2024-07-03T22:46:52.882Z |
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