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, Jahrgang 17, Nr. 3, 3, 01.03.2011, S. 374-383.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -