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Development of dendritic cell loaded MAGE-A2 long peptide; a potential target for tumor-specific T cell-mediated prostate cancer immunotherapy

BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. Immunotherapy is an emerging treatment modality for cancers that harnesses the immune system’s ability to eliminate tumor cells. In particular, dendritic cell (DC) vaccines, have demonstrated...

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Autores principales: Bakhshi, Parisa, Nourizadeh, Maryam, Sharifi, Laleh, Farajollahi, Mohammad M., Mohsenzadegan, Monireh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638778/
https://www.ncbi.nlm.nih.gov/pubmed/37951911
http://dx.doi.org/10.1186/s12935-023-03108-0
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author Bakhshi, Parisa
Nourizadeh, Maryam
Sharifi, Laleh
Farajollahi, Mohammad M.
Mohsenzadegan, Monireh
author_facet Bakhshi, Parisa
Nourizadeh, Maryam
Sharifi, Laleh
Farajollahi, Mohammad M.
Mohsenzadegan, Monireh
author_sort Bakhshi, Parisa
collection PubMed
description BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. Immunotherapy is an emerging treatment modality for cancers that harnesses the immune system’s ability to eliminate tumor cells. In particular, dendritic cell (DC) vaccines, have demonstrated promise in eliciting a tumor-specific immune response. In this study, we investigated the potential of using DCs loaded with the MAGE-A2 long peptide to activate T cell cytotoxicity toward PCa cell lines. METHODS: Here, we generated DCs from monocytes and thoroughly characterized their phenotypic and functional properties. Then, DCs were pulsed with MAGE-A2 long peptide (LP) as an antigen source, and monitored for their transition from immature to mature DCs by assessing the expression levels of several costimulatory and maturation molecules like CD14, HLA-DR, CD40, CD11c, CD80, CD83, CD86, and CCR7. Furthermore, the ability of MAGE-A2 -LP pulsed DCs to stimulate T cell proliferation in a mixed lymphocyte reaction (MLR) setting and induction of cytotoxic T cells (CTLs) in coculture with autologous T cells were examined. Finally, CTLs were evaluated for their capacity to produce interferon-gamma (IFN-γ) and kill PCa cell lines (PC3 and LNCaP). RESULTS: The results demonstrated that the antigen-pulsed DCs exhibited a strong ability to stimulate the expansion of T cells. Moreover, the induced CTLs displayed substantial cytotoxicity against the target cells and exhibited increased IFN-γ production during activation compared to the controls. CONCLUSIONS: Overall, this innovative approach proved efficacious in targeting PCa cell lines, showcasing its potential as a foundation for the development and improved PCa cancer immunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03108-0.
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spelling pubmed-106387782023-11-11 Development of dendritic cell loaded MAGE-A2 long peptide; a potential target for tumor-specific T cell-mediated prostate cancer immunotherapy Bakhshi, Parisa Nourizadeh, Maryam Sharifi, Laleh Farajollahi, Mohammad M. Mohsenzadegan, Monireh Cancer Cell Int Research BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. Immunotherapy is an emerging treatment modality for cancers that harnesses the immune system’s ability to eliminate tumor cells. In particular, dendritic cell (DC) vaccines, have demonstrated promise in eliciting a tumor-specific immune response. In this study, we investigated the potential of using DCs loaded with the MAGE-A2 long peptide to activate T cell cytotoxicity toward PCa cell lines. METHODS: Here, we generated DCs from monocytes and thoroughly characterized their phenotypic and functional properties. Then, DCs were pulsed with MAGE-A2 long peptide (LP) as an antigen source, and monitored for their transition from immature to mature DCs by assessing the expression levels of several costimulatory and maturation molecules like CD14, HLA-DR, CD40, CD11c, CD80, CD83, CD86, and CCR7. Furthermore, the ability of MAGE-A2 -LP pulsed DCs to stimulate T cell proliferation in a mixed lymphocyte reaction (MLR) setting and induction of cytotoxic T cells (CTLs) in coculture with autologous T cells were examined. Finally, CTLs were evaluated for their capacity to produce interferon-gamma (IFN-γ) and kill PCa cell lines (PC3 and LNCaP). RESULTS: The results demonstrated that the antigen-pulsed DCs exhibited a strong ability to stimulate the expansion of T cells. Moreover, the induced CTLs displayed substantial cytotoxicity against the target cells and exhibited increased IFN-γ production during activation compared to the controls. CONCLUSIONS: Overall, this innovative approach proved efficacious in targeting PCa cell lines, showcasing its potential as a foundation for the development and improved PCa cancer immunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03108-0. BioMed Central 2023-11-11 /pmc/articles/PMC10638778/ /pubmed/37951911 http://dx.doi.org/10.1186/s12935-023-03108-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/ Open Access This 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
Bakhshi, Parisa
Nourizadeh, Maryam
Sharifi, Laleh
Farajollahi, Mohammad M.
Mohsenzadegan, Monireh
Development of dendritic cell loaded MAGE-A2 long peptide; a potential target for tumor-specific T cell-mediated prostate cancer immunotherapy
title Development of dendritic cell loaded MAGE-A2 long peptide; a potential target for tumor-specific T cell-mediated prostate cancer immunotherapy
title_full Development of dendritic cell loaded MAGE-A2 long peptide; a potential target for tumor-specific T cell-mediated prostate cancer immunotherapy
title_fullStr Development of dendritic cell loaded MAGE-A2 long peptide; a potential target for tumor-specific T cell-mediated prostate cancer immunotherapy
title_full_unstemmed Development of dendritic cell loaded MAGE-A2 long peptide; a potential target for tumor-specific T cell-mediated prostate cancer immunotherapy
title_short Development of dendritic cell loaded MAGE-A2 long peptide; a potential target for tumor-specific T cell-mediated prostate cancer immunotherapy
title_sort development of dendritic cell loaded mage-a2 long peptide; a potential target for tumor-specific t cell-mediated prostate cancer immunotherapy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638778/
https://www.ncbi.nlm.nih.gov/pubmed/37951911
http://dx.doi.org/10.1186/s12935-023-03108-0
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