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Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma
Due to immunosuppressive properties and confirmed tropism towards cancer cells mesenchymal stromal cells (MSC) have been used in many trials. In our study we used these cells as carriers of IL-12 in the treatment of mice with primary and metastatic B16-F10 melanomas. IL-12 has confirmed anti-cancer...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443548/ https://www.ncbi.nlm.nih.gov/pubmed/34526531 http://dx.doi.org/10.1038/s41598-021-97435-9 |
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author | Kułach, Natalia Pilny, Ewelina Cichoń, Tomasz Czapla, Justyna Jarosz-Biej, Magdalena Rusin, Marek Drzyzga, Alina Matuszczak, Sybilla Szala, Stanisław Smolarczyk, Ryszard |
author_facet | Kułach, Natalia Pilny, Ewelina Cichoń, Tomasz Czapla, Justyna Jarosz-Biej, Magdalena Rusin, Marek Drzyzga, Alina Matuszczak, Sybilla Szala, Stanisław Smolarczyk, Ryszard |
author_sort | Kułach, Natalia |
collection | PubMed |
description | Due to immunosuppressive properties and confirmed tropism towards cancer cells mesenchymal stromal cells (MSC) have been used in many trials. In our study we used these cells as carriers of IL-12 in the treatment of mice with primary and metastatic B16-F10 melanomas. IL-12 has confirmed anti-cancer activity, induces a strong immune response against cancer cells and acts as an anti-angiogenic agent. A major limitation of the use of IL-12 in therapy is its systemic toxicity. The aim of the work was to develop a system in which cytokine may be administered intravenously without toxic side effects. In this study MSC were used as carriers of the IL-12. We confirmed antitumor effectiveness of the cells secreting IL-12 (MSC/IL-12) in primary and metastatic murine melanoma models. We observed inhibition of tumor growth and a significant reduction in the number of metastases in mice after MSC/IL-12 administration. MSC/IL-12 decreased vascular density and increased the number of anticancer M1 macrophages and CD8(+) cytotoxic T lymphocytes in tumors of treated mice. To summarize, we showed that MSC are an effective, safe carrier of IL-12 cytokine. Administered systemically they exert therapeutic properties of IL-12 cytokine without toxicity. Therapeutic effect may be a result of pleiotropic (proinflammatory and anti-angiogenic) properties of IL-12 released by modified MSC. |
format | Online Article Text |
id | pubmed-8443548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84435482021-09-20 Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma Kułach, Natalia Pilny, Ewelina Cichoń, Tomasz Czapla, Justyna Jarosz-Biej, Magdalena Rusin, Marek Drzyzga, Alina Matuszczak, Sybilla Szala, Stanisław Smolarczyk, Ryszard Sci Rep Article Due to immunosuppressive properties and confirmed tropism towards cancer cells mesenchymal stromal cells (MSC) have been used in many trials. In our study we used these cells as carriers of IL-12 in the treatment of mice with primary and metastatic B16-F10 melanomas. IL-12 has confirmed anti-cancer activity, induces a strong immune response against cancer cells and acts as an anti-angiogenic agent. A major limitation of the use of IL-12 in therapy is its systemic toxicity. The aim of the work was to develop a system in which cytokine may be administered intravenously without toxic side effects. In this study MSC were used as carriers of the IL-12. We confirmed antitumor effectiveness of the cells secreting IL-12 (MSC/IL-12) in primary and metastatic murine melanoma models. We observed inhibition of tumor growth and a significant reduction in the number of metastases in mice after MSC/IL-12 administration. MSC/IL-12 decreased vascular density and increased the number of anticancer M1 macrophages and CD8(+) cytotoxic T lymphocytes in tumors of treated mice. To summarize, we showed that MSC are an effective, safe carrier of IL-12 cytokine. Administered systemically they exert therapeutic properties of IL-12 cytokine without toxicity. Therapeutic effect may be a result of pleiotropic (proinflammatory and anti-angiogenic) properties of IL-12 released by modified MSC. Nature Publishing Group UK 2021-09-15 /pmc/articles/PMC8443548/ /pubmed/34526531 http://dx.doi.org/10.1038/s41598-021-97435-9 Text en © The Author(s) 2021 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/) . |
spellingShingle | Article Kułach, Natalia Pilny, Ewelina Cichoń, Tomasz Czapla, Justyna Jarosz-Biej, Magdalena Rusin, Marek Drzyzga, Alina Matuszczak, Sybilla Szala, Stanisław Smolarczyk, Ryszard Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma |
title | Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma |
title_full | Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma |
title_fullStr | Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma |
title_full_unstemmed | Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma |
title_short | Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma |
title_sort | mesenchymal stromal cells as carriers of il-12 reduce primary and metastatic tumors of murine melanoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443548/ https://www.ncbi.nlm.nih.gov/pubmed/34526531 http://dx.doi.org/10.1038/s41598-021-97435-9 |
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