Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926263/ https://www.ncbi.nlm.nih.gov/pubmed/24528541 http://dx.doi.org/10.1186/1479-5876-12-45 |
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author | Wilhelm, Martin Smetak, Manfred Schaefer-Eckart, Kerstin Kimmel, Brigitte Birkmann, Josef Einsele, Hermann Kunzmann, Volker |
author_facet | Wilhelm, Martin Smetak, Manfred Schaefer-Eckart, Kerstin Kimmel, Brigitte Birkmann, Josef Einsele, Hermann Kunzmann, Volker |
author_sort | Wilhelm, Martin |
collection | PubMed |
description | 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 × 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 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. 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. |
format | Online Article Text |
id | pubmed-3926263 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39262632014-02-18 Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells Wilhelm, Martin Smetak, Manfred Schaefer-Eckart, Kerstin Kimmel, Brigitte Birkmann, Josef Einsele, Hermann Kunzmann, Volker J Transl Med Research 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 × 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 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. 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. BioMed Central 2014-02-15 /pmc/articles/PMC3926263/ /pubmed/24528541 http://dx.doi.org/10.1186/1479-5876-12-45 Text en Copyright © 2014 Wilhelm et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Wilhelm, Martin Smetak, Manfred Schaefer-Eckart, Kerstin Kimmel, Brigitte Birkmann, Josef Einsele, Hermann Kunzmann, Volker Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells |
title | Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells |
title_full | Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells |
title_fullStr | Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells |
title_full_unstemmed | Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells |
title_short | Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells |
title_sort | successful adoptive transfer and in vivo expansion of haploidentical γδ t cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926263/ https://www.ncbi.nlm.nih.gov/pubmed/24528541 http://dx.doi.org/10.1186/1479-5876-12-45 |
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