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In Vitro Generation of BK polyomavirus-specific T cells for adoptive cell therapy in refractory cystitis hemorrhagic patients after hematopoietic stem cell transplantation

INTRODUCTION: BKPyV associated hemorrhagic cystitis (BKPyV-HC) is a major and prevalent outcome of hematopoietic stem cell transplantation (HSCT) with no standard treatment option. Adoptive T cell therapy (ACT) against transplant-associated viruses has shown promising potential. We sought to produce...

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Autores principales: Najafabadi, Maryam Mohammadi, Soleimani, Masoud, Ahmadvand, Mohammad, Zomorrod, Mina Soufi, Mousavi, Seied Asadollah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188250/
https://www.ncbi.nlm.nih.gov/pubmed/35689183
http://dx.doi.org/10.1186/s12865-022-00497-1
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author Najafabadi, Maryam Mohammadi
Soleimani, Masoud
Ahmadvand, Mohammad
Zomorrod, Mina Soufi
Mousavi, Seied Asadollah
author_facet Najafabadi, Maryam Mohammadi
Soleimani, Masoud
Ahmadvand, Mohammad
Zomorrod, Mina Soufi
Mousavi, Seied Asadollah
author_sort Najafabadi, Maryam Mohammadi
collection PubMed
description INTRODUCTION: BKPyV associated hemorrhagic cystitis (BKPyV-HC) is a major and prevalent outcome of hematopoietic stem cell transplantation (HSCT) with no standard treatment option. Adoptive T cell therapy (ACT) against transplant-associated viruses has shown promising potential. We sought to produce virus-specific T cells (VSTs) against BKPyV with the aim of treating refractory HSCT-associated HC. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors were isolated by Ficoll-Hypaque density gradient centrifugation. BKPyV-pulsed, monocyte-derived dendritic cells (mo-DCs) and T cells were co-cultured and expanded over 2–3 weeks with the addition of IL-2. The T cells were examined for various functional assays. RESULTS: Comparison analysis of Carboxyfluorescein diacetate succinimidyl ester (CFSE) indicated that the percentage of proliferated cells were significantly higher in donors (49.62 ± 7.09%) than controls (7.96 ± 4.55%). Furthermore, expanded T cells exhibited specificity to BKPyV antigens by IFN-γ ELISPOT assay. The expanded cells showed cytotoxic function versus human lymphoblastoid cell line (LCL). Final VST products mainly comprised of CD8/CD69 double-positive T cells, which were significantly higher in donors (46.8 ± 7.1%) than controls (16.91 ± 3.40%). CONCLUSION: In this study we demonstrated the feasibility of producing functional BKPyV-specific T cells in healthy donors using BKPyV PepMixes. These functional cells were able to proliferate and produce IFN-γ cytokine in response to BKPyV PepMixes. In addition, these T cells had cytotoxic ability against BKPyV antigen-expressing target cells.
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spelling pubmed-91882502022-06-12 In Vitro Generation of BK polyomavirus-specific T cells for adoptive cell therapy in refractory cystitis hemorrhagic patients after hematopoietic stem cell transplantation Najafabadi, Maryam Mohammadi Soleimani, Masoud Ahmadvand, Mohammad Zomorrod, Mina Soufi Mousavi, Seied Asadollah BMC Immunol Research INTRODUCTION: BKPyV associated hemorrhagic cystitis (BKPyV-HC) is a major and prevalent outcome of hematopoietic stem cell transplantation (HSCT) with no standard treatment option. Adoptive T cell therapy (ACT) against transplant-associated viruses has shown promising potential. We sought to produce virus-specific T cells (VSTs) against BKPyV with the aim of treating refractory HSCT-associated HC. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors were isolated by Ficoll-Hypaque density gradient centrifugation. BKPyV-pulsed, monocyte-derived dendritic cells (mo-DCs) and T cells were co-cultured and expanded over 2–3 weeks with the addition of IL-2. The T cells were examined for various functional assays. RESULTS: Comparison analysis of Carboxyfluorescein diacetate succinimidyl ester (CFSE) indicated that the percentage of proliferated cells were significantly higher in donors (49.62 ± 7.09%) than controls (7.96 ± 4.55%). Furthermore, expanded T cells exhibited specificity to BKPyV antigens by IFN-γ ELISPOT assay. The expanded cells showed cytotoxic function versus human lymphoblastoid cell line (LCL). Final VST products mainly comprised of CD8/CD69 double-positive T cells, which were significantly higher in donors (46.8 ± 7.1%) than controls (16.91 ± 3.40%). CONCLUSION: In this study we demonstrated the feasibility of producing functional BKPyV-specific T cells in healthy donors using BKPyV PepMixes. These functional cells were able to proliferate and produce IFN-γ cytokine in response to BKPyV PepMixes. In addition, these T cells had cytotoxic ability against BKPyV antigen-expressing target cells. BioMed Central 2022-06-10 /pmc/articles/PMC9188250/ /pubmed/35689183 http://dx.doi.org/10.1186/s12865-022-00497-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Najafabadi, Maryam Mohammadi
Soleimani, Masoud
Ahmadvand, Mohammad
Zomorrod, Mina Soufi
Mousavi, Seied Asadollah
In Vitro Generation of BK polyomavirus-specific T cells for adoptive cell therapy in refractory cystitis hemorrhagic patients after hematopoietic stem cell transplantation
title In Vitro Generation of BK polyomavirus-specific T cells for adoptive cell therapy in refractory cystitis hemorrhagic patients after hematopoietic stem cell transplantation
title_full In Vitro Generation of BK polyomavirus-specific T cells for adoptive cell therapy in refractory cystitis hemorrhagic patients after hematopoietic stem cell transplantation
title_fullStr In Vitro Generation of BK polyomavirus-specific T cells for adoptive cell therapy in refractory cystitis hemorrhagic patients after hematopoietic stem cell transplantation
title_full_unstemmed In Vitro Generation of BK polyomavirus-specific T cells for adoptive cell therapy in refractory cystitis hemorrhagic patients after hematopoietic stem cell transplantation
title_short In Vitro Generation of BK polyomavirus-specific T cells for adoptive cell therapy in refractory cystitis hemorrhagic patients after hematopoietic stem cell transplantation
title_sort in vitro generation of bk polyomavirus-specific t cells for adoptive cell therapy in refractory cystitis hemorrhagic patients after hematopoietic stem cell transplantation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188250/
https://www.ncbi.nlm.nih.gov/pubmed/35689183
http://dx.doi.org/10.1186/s12865-022-00497-1
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