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Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells

Please always quote using this URN: urn:nbn:de:bvb:20-opus-117290
  • 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 depletionBackground: 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.show moreshow less

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Metadaten
Author: Martin Wilhelm, Manfred Smetak, Kerstin Schaefer-Eckart, Brigitte Kimmel, Josef Birkmann, Hermann Einsele, Volker Kunzmann
URN:urn:nbn:de:bvb:20-opus-117290
Document Type:Journal article
Faculties:Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):Journal of Translational Medicine
Year of Completion:2014
Volume:12
Issue:45
Source:Journal of Translational Medicine 2014 12:45. doi:10.1186/1479-5876-12-45
DOI:https://doi.org/10.1186/1479-5876-12-45
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24528541
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:CD4(+); Interleukin-2; NK cells; acute myeloid-leukemia; adoptive transfer; biophosphonate; cancer; haploidentical γδ T lymphocytes; immunotherapy; in vivo cell expansion; infusion; innate immunity; stimulation
Release Date:2015/08/18
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung