Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma

Abstract 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 ant...

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Autores principales:	Natalia Kułach, Ewelina Pilny, Tomasz Cichoń, Justyna Czapla, Magdalena Jarosz-Biej, Marek Rusin, Alina Drzyzga, Sybilla Matuszczak, Stanisław Szala, Ryszard Smolarczyk
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bcd4d466f3a84e96830b0f5ae3e9063f
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spelling	oai:doaj.org-article:bcd4d466f3a84e96830b0f5ae3e9063f2021-12-02T15:15:44ZMesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma10.1038/s41598-021-97435-92045-2322https://doaj.org/article/bcd4d466f3a84e96830b0f5ae3e9063f2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97435-9https://doaj.org/toc/2045-2322Abstract 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.Natalia KułachEwelina PilnyTomasz CichońJustyna CzaplaMagdalena Jarosz-BiejMarek RusinAlina DrzyzgaSybilla MatuszczakStanisław SzalaRyszard SmolarczykNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Natalia Kułach Ewelina Pilny Tomasz Cichoń Justyna Czapla Magdalena Jarosz-Biej Marek Rusin Alina Drzyzga Sybilla Matuszczak Stanisław Szala Ryszard Smolarczyk Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma
description	Abstract 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	article
author	Natalia Kułach Ewelina Pilny Tomasz Cichoń Justyna Czapla Magdalena Jarosz-Biej Marek Rusin Alina Drzyzga Sybilla Matuszczak Stanisław Szala Ryszard Smolarczyk
author_facet	Natalia Kułach Ewelina Pilny Tomasz Cichoń Justyna Czapla Magdalena Jarosz-Biej Marek Rusin Alina Drzyzga Sybilla Matuszczak Stanisław Szala Ryszard Smolarczyk
author_sort	Natalia Kułach
title	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_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_sort	mesenchymal stromal cells as carriers of il-12 reduce primary and metastatic tumors of murine melanoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bcd4d466f3a84e96830b0f5ae3e9063f
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Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma

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