TY - JOUR A1 - Wilhelm, Martin A1 - Smetak, Manfred A1 - Schaefer-Eckart, Kerstin A1 - Kimmel, Brigitte A1 - Birkmann, Josef A1 - Einsele, Hermann A1 - Kunzmann, Volker T1 - Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells T2 - Journal of Translational Medicine N2 - 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 gamma delta 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 (R) device according to the manufacturer's instructions. On average, patients received 2.17 x 10(6)/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/m(2) 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 1.0x10(6) IU/m(2) IL-2 on day +1 until day +6 for the induction of gamma delta 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. Conclusion: 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. KW - NK cells KW - in vivo cell expansion KW - haploidentical γδ T lymphocytes KW - adoptive transfer KW - CD4(+) KW - innate immunity KW - stimulation KW - acute myeloid-leukemia KW - immunotherapy KW - cancer KW - infusion KW - Interleukin-2 KW - biophosphonate Y1 - 2014 UR - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/11729 UR - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-117290 VL - 12 IS - 45 ER -