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

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
E KlyuchnikovN Kröger

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(®)) 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...Continue Reading

References

Jan 5, 2002·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·A ShimoniS Giralt
Dec 5, 2002·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Robert J SoifferJerome Ritz
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Aug 20, 2008·Bone Marrow Transplantation·M Tomblyn, H M Lazarus

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Citations

Feb 14, 2012·Bone Marrow Transplantation·W BensingerD Maloney
Sep 27, 2013·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Nicolaus KrögerDjordje Atanackovic
Jan 13, 2021·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christoph SchmidGesine Bug

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