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Generation of memory T cells for adoptive transfer using clinical-grade anti-CD62L magnetic beads

Bone Marrow Transplantation volume 50, pages 1358–1364 (2015)Cite this article

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A Corrigendum to this article was published on 06 April 2016

Abstract

Pre-clinical studies of allogeneic stem cell transplantation suggest that depletion of naive T cells from donor lymphocytes will reduce the risk of GvHD but preserve immunity to infectious pathogens. In this study, we have established a clinical-grade protocol under good manufacturing practice conditions for purging CD62L+ naive T cells from steady-state leukapheresis products using the CliniMACS system. The efficacy of immunomagnetic CD62L depletion was assessed by analysis of cell composition and functional immune responses. A median 2.9 log CD62L depletion was achieved with no evidence of CD62L shedding during the procedure and a mean T-cell yield of 47%. CD62L− cells comprised an equal mix of CD4+ and CD8+ T cells, with elimination of B cells but maintenance of regulatory T cells and natural killer cell populations. CD62L-depleted T cells were predominantly CD45RA− and CD45RA+ effector memory (>90%) and contained the bulk of pentamer-staining antivirus-specific T cells. Functional assessment of CD62L− cells revealed the maintenance of antiviral T-cell reactivity and a reduction in the alloreactive immune response compared with unmanipulated cells. Clinical-grade depletion of naive T cells using immunomagnetic CD62L beads from steady-state leukapheresis products is highly efficient and generates cells suitable for adoptive transfer in the context of clinical trials.

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Acknowledgements

This study was supported by Leukaemia Lymphoma Research, UK (RC), and by Fundação para a Ciência e a Tecnologia, Portugal (PSES). We thank Miltenyi Biotec for providing the CD62L clinical reagents and depletion kits for this study, and Svenja Siemer for her assistance with performing immune assays.

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Author notes

  1. S Verfuerth and P S E Sousa: These authors contributed equally to this work.

  2. R Chakraverty and E R Samuel: Joint senior authors.

Authors and Affiliations

  1. Transplantation Immunology Group, Institute of Cancer Studies, University College London Medical School, Royal Free Campus, London, UK

    S Verfuerth, P S E Sousa & R Chakraverty

  2. Oncohematology Research Group, Navarrabiomed-Miguel Servet Foundation, Pamplona, Spain

    L Beloki

  3. The Centre for Cell, Gene and Tissue Therapeutics, Institute of Immunity and Transplantation, University College London Medical School, Royal Free Campus, London, UK

    M Murray, M D Peters, M W Lowdell & E R Samuel

  4. Department of Haematology, Royal Free London NHS Foundation Trust, London, UK

    S Mackinnon & M W Lowdell

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  1. S Verfuerth
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  2. P S E Sousa
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Correspondence to E R Samuel.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on Bone Marrow Transplantation website

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Verfuerth, S., Sousa, P., Beloki, L. et al. Generation of memory T cells for adoptive transfer using clinical-grade anti-CD62L magnetic beads. Bone Marrow Transplant 50, 1358–1364 (2015). https://doi.org/10.1038/bmt.2015.135

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