Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kułach, Natalia, Pilny, Ewelina, Cichoń, Tomasz, Czapla, Justyna, Jarosz-Biej, Magdalena, Rusin, Marek, Drzyzga, Alina, Matuszczak, Sybilla, Szala, Stanisław, Smolarczyk, Ryszard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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
_version_ 1783753204380467200
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
work_keys_str_mv AT kułachnatalia mesenchymalstromalcellsascarriersofil12reduceprimaryandmetastatictumorsofmurinemelanoma
AT pilnyewelina mesenchymalstromalcellsascarriersofil12reduceprimaryandmetastatictumorsofmurinemelanoma
AT cichontomasz mesenchymalstromalcellsascarriersofil12reduceprimaryandmetastatictumorsofmurinemelanoma
AT czaplajustyna mesenchymalstromalcellsascarriersofil12reduceprimaryandmetastatictumorsofmurinemelanoma
AT jaroszbiejmagdalena mesenchymalstromalcellsascarriersofil12reduceprimaryandmetastatictumorsofmurinemelanoma
AT rusinmarek mesenchymalstromalcellsascarriersofil12reduceprimaryandmetastatictumorsofmurinemelanoma
AT drzyzgaalina mesenchymalstromalcellsascarriersofil12reduceprimaryandmetastatictumorsofmurinemelanoma
AT matuszczaksybilla mesenchymalstromalcellsascarriersofil12reduceprimaryandmetastatictumorsofmurinemelanoma
AT szalastanisław mesenchymalstromalcellsascarriersofil12reduceprimaryandmetastatictumorsofmurinemelanoma
AT smolarczykryszard mesenchymalstromalcellsascarriersofil12reduceprimaryandmetastatictumorsofmurinemelanoma