title: Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells.
abstract: BACKGROUND
  The primary aim of this pilot study was to determine the feasibility and safety of an adoptive transfer and in vivo expansion of human haploidentical γδ T lymphocytes.
  
  
  METHODS
  Patients with advanced haematological malignancies who are not eligible for allogeneic transplantation received peripheral blood mononuclear cells from half-matched family donors. For that, a single unstimulated leukapheresis product was incubated with both the anti-CD4 and anti-CD8 antibodies conjugated to paramagnetic particles. The depletion procedure was performed on a fully automated CliniMACS device according to the manufacturer's instructions. On average, patients received 2.17 × 10⁶/kg (range 0.9-3.48) γδ T cells with <1% CD4- or CD8-positive cells remaining in the product. All patients received prior lymphopenia-inducing chemotherapy (fludarabine 20-25 mg/m² day -6 until day -2 and cyclophosphamide 30-60 mg/kg day -6 and -5) and were treated with 4 mg zoledronate on day 0 and 1.0 x 10⁶ IU/m² IL-2 on day +1 until day +6 for the induction of γδ T cell proliferation in vivo.
  
  
  RESULTS
  This resulted in a marked in vivo expansion of donor γδ T cells and, to a lower extent, natural killer cells and double-negative αβ T cells (mean 68-fold, eight-fold, and eight-fold, respectively). Proliferation peaked by around day +8 and donor cells persisted up to 28 days. Although refractory to all prior therapies, three out of four patients achieved a complete remission, which lasted for 8 months in a patient with plasma cell leukaemia. One patient died from an infection 6 weeks after treatment.
  
  
  CONCLUSIONS
  This pilot study shows that adoptive transfer and in vivo expansion of haploidentical γδ T lymphocytes is feasible and suggests a potential role of these cells in the treatment of haematological diseases.
authors: Klinikum Nürnberg, Medizinische Klinik 5, Prof-Ernst-Nathan-Str, 1, D-90340 Nuernberg, Germany. martin.wilhelm@klinikum-nuernberg.de.
authors: Martin
authors: M
authors: Wilhelm
authors: Manfred
authors: M
authors: Smetak
authors: Kerstin
authors: K
authors: Schaefer-Eckart
authors: Brigitte
authors: B
authors: Kimmel
authors: Josef
authors: J
authors: Birkmann
authors: Hermann
authors: H
authors: Einsele
authors: Volker
authors: V
authors: Kunzmann
mesh_terms: D019264:Adoptive Transfer / Q000009:adverse effects; D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology*; D016896:Treatment Outcome
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta