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Purification of CD4+ T cells for adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation

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Purification of CD4+ T cells for adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation. / Klyuchnikov, Evgeny; Sputtek, Andreas; Slesarchuk, Olga; Lioznov, Michael; Stübig, Thomas; Bacher, Ulrike; Amtsfeld, Gitta; Merle, Edeltraut; Reckhaus, Marie-Luise; Fehse, Boris; Wolschke, Christine; Adjalle, Raissa; Ayuketang Ayuk, Francis; Zander, Axel R.; Kröger, Nicolaus.

In: BIOL BLOOD MARROW TR, Vol. 17, No. 3, 3, 01.03.2011, p. 374-383.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Klyuchnikov, E, Sputtek, A, Slesarchuk, O, Lioznov, M, Stübig, T, Bacher, U, Amtsfeld, G, Merle, E, Reckhaus, M-L, Fehse, B, Wolschke, C, Adjalle, R, Ayuketang Ayuk, F, Zander, AR & Kröger, N 2011, 'Purification of CD4+ T cells for adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation', BIOL BLOOD MARROW TR, vol. 17, no. 3, 3, pp. 374-383. https://doi.org/10.1016/j.bbmt.2010.07.003

APA

Klyuchnikov, E., Sputtek, A., Slesarchuk, O., Lioznov, M., Stübig, T., Bacher, U., Amtsfeld, G., Merle, E., Reckhaus, M-L., Fehse, B., Wolschke, C., Adjalle, R., Ayuketang Ayuk, F., Zander, A. R., & Kröger, N. (2011). Purification of CD4+ T cells for adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation. BIOL BLOOD MARROW TR, 17(3), 374-383. [3]. https://doi.org/10.1016/j.bbmt.2010.07.003

Vancouver

Klyuchnikov E, Sputtek A, Slesarchuk O, Lioznov M, Stübig T, Bacher U et al. Purification of CD4+ T cells for adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation. BIOL BLOOD MARROW TR. 2011 Mar 1;17(3):374-383. 3. https://doi.org/10.1016/j.bbmt.2010.07.003

Bibtex

@article{da60ba08e915432abe37436eaad544ab,
title = "Purification of CD4+ T cells for adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation",
abstract = "Donor lymphocyte infusions (DLIs) are used for adoptive immunotherapy to prevent or treat relapse and infectious complications after allogeneic hematopoietic stem cell transplantation (HSCT). Unmanipulated DLIs are associated with a risk of graft-versus-host disease (GVHD), probably related to CD8(+) T cell activity. We investigated an automated clinical-scale human-CD4(+)-cell purification method to deplete CD8(+) cells. Twenty-four stem cell recipients received a total of 24 leukapheresis products being enriched for CD4(+) cells using magnetic associated cell sorting (MACS) with an automated device (CliniMACS({\textregistered})) before DLIs. MACS resulted in a mean CD4(+) cell count of 16 × 10(6)/kg bw corresponding to 3.4-fold CD4(+) cell enrichment. Mean yield and purity of CD45(+)CD3(+)CD4(+)CD14(-)7AAD(-) were 74% ± 23% and 82% ± 11%, respectively. Median initial dose of DLIs was 1.1 × 10(6) CD4(+)/kg. During a median follow-up of 25 months, 7 (30%) patients experienced GVHD (acute II-IV: n = 4, 17%; acute III-IV: n = 2, 8%; chronic limited: n = 2, 8%; chronic extensive: n = 1, 4%). Thirteen of 21 further evaluable patients (62%) showed measurable clinical response, 2 patients with therapy refractory infectious complications (HSV) showed remarkable immunologic improvement. Automated enrichment of CD4(+) by magnetic cell sorting provides an efficient and rapid method for processing donor lymphocytes. Additional studies should further investigate this approach in terms of efficacy and the risk of GVHD.",
keywords = "Adult, Aged, CD4-Positive T-Lymphocytes, Cohort Studies, Female, Follow-Up Studies, Graft vs Host Disease, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Immunomagnetic Separation, Immunotherapy, Adoptive, Male, Middle Aged, Multiple Myeloma, Opportunistic Infections, Recurrence, Retrospective Studies, Survival Analysis, Young Adult",
author = "Evgeny Klyuchnikov and Andreas Sputtek and Olga Slesarchuk and Michael Lioznov and Thomas St{\"u}big and Ulrike Bacher and Gitta Amtsfeld and Edeltraut Merle and Marie-Luise Reckhaus and Boris Fehse and Christine Wolschke and Raissa Adjalle and {Ayuketang Ayuk}, Francis and Zander, {Axel R.} and Nicolaus Kr{\"o}ger",
note = "Copyright {\textcopyright} 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.",
year = "2011",
month = mar,
day = "1",
doi = "10.1016/j.bbmt.2010.07.003",
language = "English",
volume = "17",
pages = "374--383",
journal = "BIOL BLOOD MARROW TR",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Purification of CD4+ T cells for adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation

AU - Klyuchnikov, Evgeny

AU - Sputtek, Andreas

AU - Slesarchuk, Olga

AU - Lioznov, Michael

AU - Stübig, Thomas

AU - Bacher, Ulrike

AU - Amtsfeld, Gitta

AU - Merle, Edeltraut

AU - Reckhaus, Marie-Luise

AU - Fehse, Boris

AU - Wolschke, Christine

AU - Adjalle, Raissa

AU - Ayuketang Ayuk, Francis

AU - Zander, Axel R.

AU - Kröger, Nicolaus

N1 - Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

PY - 2011/3/1

Y1 - 2011/3/1

N2 - Donor lymphocyte infusions (DLIs) are used for adoptive immunotherapy to prevent or treat relapse and infectious complications after allogeneic hematopoietic stem cell transplantation (HSCT). Unmanipulated DLIs are associated with a risk of graft-versus-host disease (GVHD), probably related to CD8(+) T cell activity. We investigated an automated clinical-scale human-CD4(+)-cell purification method to deplete CD8(+) cells. Twenty-four stem cell recipients received a total of 24 leukapheresis products being enriched for CD4(+) cells using magnetic associated cell sorting (MACS) with an automated device (CliniMACS(®)) before DLIs. MACS resulted in a mean CD4(+) cell count of 16 × 10(6)/kg bw corresponding to 3.4-fold CD4(+) cell enrichment. Mean yield and purity of CD45(+)CD3(+)CD4(+)CD14(-)7AAD(-) were 74% ± 23% and 82% ± 11%, respectively. Median initial dose of DLIs was 1.1 × 10(6) CD4(+)/kg. During a median follow-up of 25 months, 7 (30%) patients experienced GVHD (acute II-IV: n = 4, 17%; acute III-IV: n = 2, 8%; chronic limited: n = 2, 8%; chronic extensive: n = 1, 4%). Thirteen of 21 further evaluable patients (62%) showed measurable clinical response, 2 patients with therapy refractory infectious complications (HSV) showed remarkable immunologic improvement. Automated enrichment of CD4(+) by magnetic cell sorting provides an efficient and rapid method for processing donor lymphocytes. Additional studies should further investigate this approach in terms of efficacy and the risk of GVHD.

AB - Donor lymphocyte infusions (DLIs) are used for adoptive immunotherapy to prevent or treat relapse and infectious complications after allogeneic hematopoietic stem cell transplantation (HSCT). Unmanipulated DLIs are associated with a risk of graft-versus-host disease (GVHD), probably related to CD8(+) T cell activity. We investigated an automated clinical-scale human-CD4(+)-cell purification method to deplete CD8(+) cells. Twenty-four stem cell recipients received a total of 24 leukapheresis products being enriched for CD4(+) cells using magnetic associated cell sorting (MACS) with an automated device (CliniMACS(®)) before DLIs. MACS resulted in a mean CD4(+) cell count of 16 × 10(6)/kg bw corresponding to 3.4-fold CD4(+) cell enrichment. Mean yield and purity of CD45(+)CD3(+)CD4(+)CD14(-)7AAD(-) were 74% ± 23% and 82% ± 11%, respectively. Median initial dose of DLIs was 1.1 × 10(6) CD4(+)/kg. During a median follow-up of 25 months, 7 (30%) patients experienced GVHD (acute II-IV: n = 4, 17%; acute III-IV: n = 2, 8%; chronic limited: n = 2, 8%; chronic extensive: n = 1, 4%). Thirteen of 21 further evaluable patients (62%) showed measurable clinical response, 2 patients with therapy refractory infectious complications (HSV) showed remarkable immunologic improvement. Automated enrichment of CD4(+) by magnetic cell sorting provides an efficient and rapid method for processing donor lymphocytes. Additional studies should further investigate this approach in terms of efficacy and the risk of GVHD.

KW - Adult

KW - Aged

KW - CD4-Positive T-Lymphocytes

KW - Cohort Studies

KW - Female

KW - Follow-Up Studies

KW - Graft vs Host Disease

KW - Hematologic Neoplasms

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Immunomagnetic Separation

KW - Immunotherapy, Adoptive

KW - Male

KW - Middle Aged

KW - Multiple Myeloma

KW - Opportunistic Infections

KW - Recurrence

KW - Retrospective Studies

KW - Survival Analysis

KW - Young Adult

U2 - 10.1016/j.bbmt.2010.07.003

DO - 10.1016/j.bbmt.2010.07.003

M3 - SCORING: Journal article

C2 - 20637880

VL - 17

SP - 374

EP - 383

JO - BIOL BLOOD MARROW TR

JF - BIOL BLOOD MARROW TR

SN - 1083-8791

IS - 3

M1 - 3

ER -