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首页> 外文期刊>Experimental dermatology >Anti-tumor activity of mesenchymal stem cells producing IL-12 in a mouse melanoma model.
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Anti-tumor activity of mesenchymal stem cells producing IL-12 in a mouse melanoma model.

机译:在小鼠黑色素瘤模型中产生IL-12的间充质干细胞的抗肿瘤活性。

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摘要

Mesenchymal stem cells (MSCs) represent a new tool for delivery of therapeutic agents to tumor cells. In this study, we have evaluated the anti-tumor activity of human MSCs stably transduced with a retroviral vector expressing the cytokine interleukin-12 (IL-12) in a mouse melanoma model. Application of MSC(IL-12) but not control MSCs strongly reduced the formation of lung metastases of B16F10 melanoma cells. The activity of the MSC(IL-12) cells was dependent on the presence of natural killer (NK) cells in this experimental setting. Further, MSC(IL-12) cells elicited a pronounced retardation of tumor growth and led to prolonged survival when injected into established subcutaneous melanoma in a therapeutic regimen. The therapeutic effect of the MSC(IL-12) was in part mediated by CD8(+) T cells, while NK cells and CD4(+) T cells appeared to play a minor role. The anti-tumor effect of MSC(IL-12) cells was of similar efficiency as observed for application of naked plasmid DNA encoding IL-12. The presented data demonstrate that these two different strategies can induce a similar therapeutic anti-tumor efficacy in the mouse melanoma tumor model.
机译:间充质干细胞(MSCs)代表了一种将治疗剂递送至肿瘤细胞的新工具。在这项研究中,我们已经评估了在小鼠黑素瘤模型中用表达细胞因子白介素12(IL-12)的逆转录病毒载体稳定转导的人MSC的抗肿瘤活性。 MSC(IL-12)而不是对照MSC的应用极大地减少了B16F10黑色素瘤细胞肺转移的形成。在此实验环境中,MSC(IL-12)细胞的活性取决于自然杀伤(NK)细胞的存在。此外,当以治疗方案注射入已建立的皮下黑色素瘤中时,MSC(IL-12)细胞引起明显的肿瘤生长延迟并导致延长的生存期。 MSC(IL-12)的治疗作用部分由CD8(+)T细胞介导,而NK细胞和CD4(+)T细胞似乎起次要作用。 MSC(IL-12)细胞的抗肿瘤作用与应用编码IL-12的裸质粒DNA观察到的效率相似。提出的数据证明这两种不同的策略可以在小鼠黑素瘤肿瘤模型中诱导相似的治疗性抗肿瘤功效。

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