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, O'Neill, A T, Mackinnon, S, Lowdell, M W, Chakraverty, R, Samuel, E R
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.10.2015
• Subjects: Adoptive transfer; Adoptive Transfer - methods; Antiviral agents; Beads; Bone marrow; CD4 antigen; CD45RA antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Clinical trials; Depletion; Drug therapy; Genetic aspects; Graft vs. host disease; Graft-versus-host reaction; Health aspects; Healthy Volunteers; Humans; Immune response; Immune system; Immunologic Memory - immunology; Immunological memory; Immunomagnetic Separation - methods; Immunoregulation; L-selectin; Leukapheresis; Lymphocytes; Lymphocytes B; Lymphocytes T; Maintenance; Memory cells; Natural killer cells; Purging; Risk factors; Steady state; Stem cell transplantation; Stem cells; T cells; 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.