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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 50; no. 10; pp. 1358 - 1364
• Main Authors: Verfuerth, S, Sousa, P S E, Beloki, L, Murray, M, Peters, M D, Mackinnon, S, Lowdell, M W, Chakraverty, R, Samuel, E R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-10-2015; Nature Publishing Group
• Subjects: 13; 13/106; 13/31; 631/250/1854/2812; 631/250/1904; Adoptive transfer; Adoptive Transfer - methods; Antiviral agents; Beads; Bone marrow; CD4 antigen; CD45RA antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Biology; Clinical trials; Depletion; Drug therapy; Genetic aspects; Graft vs. host disease; Graft-versus-host reaction; Health aspects; Healthy Volunteers; Hematology; Humans; Immune response; Immune system; Immunologic Memory - immunology; Immunological memory; Immunomagnetic Separation - methods; Immunoregulation; Internal Medicine; L-selectin; Leukapheresis; Lymphocytes; Lymphocytes B; Lymphocytes T; Maintenance; Medicine; Medicine & Public Health; Memory cells; Natural killer cells; Public Health; Purging; Risk factors; Steady state; Stem cell transplantation; Stem Cells; T cells; technical-report; Transplantation; United Kingdom
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2015.135

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.