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.
Highlights
ObjectivesThe aim of the work was to develop a system in which cytokine may be administered intravenously without toxic side effects
Modified mesenchymal stromal cells secrete IL-12 that inhibit the progression of murine B16-F10 melanoma
The probable mechanism responsible for the effectiveness of the therapy is the inhibition of angiogenesis evoked by MSC/ IL-12 cells and the increase in the percentage of M1 macrophages and CD8 T lymphocytes in the tumor tissue
Summary
The aim of the work was to develop a system in which cytokine may be administered intravenously without toxic side effects
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