title: A Good Manufacturing Practice procedure to engineer donor virus-specific T cells into potent anti-leukemic effector cells.
abstract: A sequential, two-step procedure in which T-cell-depleted allogeneic stem cell transplantation is followed by treatment with donor lymphocyte infusion at 6 months can significantly reduce the risk and severity of graft-versus-host disease, with postponed induction of the beneficial graft-versus-leukemia effect. However, patients with high-risk leukemia have a substantial risk of relapse early after transplantation, at a time when administration of donor lymphocytes has a high likelihood of resulting in graft-versus-host disease, disturbing a favorable balance between the graft-versus-leukemia effect and graft-versus-host disease. New therapeutic modalities are, therefore, required to allow early administration of T cells capable of exerting a graft-versus-leukemia effect without causing graft-versus-host disease. Here we describe the isolation of virus-specific T cells using Streptamer-based isolation technology and subsequent transfer of the minor histocompatibility antigen HA-1-specific T-cell receptor using retroviral vectors. Isolation of virus-specific T cells and subsequent transduction with HA-1-T-cell receptor resulted in rapid in vitro generation of highly pure, dual-specific T cells with potent anti-leukemic reactivity. Due to the short production procedure of only 10-14 days and the defined specificity of the T cells, administration of virus-specific T cells transduced with the HA-1-T-cell receptor as early as 8 weeks after allogeneic stem cell transplantation is feasible. (This clinical trial is registered at www.clinicaltrialsregister.eu as EudraCT number 2010-024625-20).
authors: M.M.van_Loenen@lumc.nl.
authors: Marleen M
authors: MM
authors: van Loenen
authors: Renate
authors: R
authors: de Boer
authors: Ellis
authors: E
authors: van Liempt
authors: Pauline
authors: P
authors: Meij
authors: Inge
authors: I
authors: Jedema
authors: J H Frederik
authors: JH
authors: Falkenburg
authors: Mirjam H M
authors: MH
authors: Heemskerk
mesh_terms: D019264:Adoptive Transfer; D061249:Batch Cell Culture Techniques / Q000379:methods* / Q000592:standards*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology; D006801:Humans; D018189:Immunomagnetic Separation; D007938:Leukemia / Q000276:immunology / Q000628:therapy; D008213:Lymphocyte Activation; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D014161:Transduction, Genetic; D014780:Viruses / Q000276:immunology*
chemical_list: C110615:HA-1 antigen; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D010455:Peptides; D011948:Receptors, Antigen, T-Cell