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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wilhelm, Martin, Smetak, Manfred, Schaefer-Eckart, Kerstin, Kimmel, Brigitte, Birkmann, Josef, Einsele, Hermann, Kunzmann, Volker
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
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
_version_ 1782303948051316736
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
work_keys_str_mv AT wilhelmmartin successfuladoptivetransferandinvivoexpansionofhaploidenticalgdtcells
AT smetakmanfred successfuladoptivetransferandinvivoexpansionofhaploidenticalgdtcells
AT schaefereckartkerstin successfuladoptivetransferandinvivoexpansionofhaploidenticalgdtcells
AT kimmelbrigitte successfuladoptivetransferandinvivoexpansionofhaploidenticalgdtcells
AT birkmannjosef successfuladoptivetransferandinvivoexpansionofhaploidenticalgdtcells
AT einselehermann successfuladoptivetransferandinvivoexpansionofhaploidenticalgdtcells
AT kunzmannvolker successfuladoptivetransferandinvivoexpansionofhaploidenticalgdtcells