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致敏exosomes对荷胃癌小鼠的免疫治疗作用研究
Immunotherapy of exosomes from DC transfected with mRNA of gastric cancer cells in carriedtumor mice
【摘要】 目的 了解DC在胃癌组织中的功能状态,探讨DC用于胃癌等实体瘤防治的可能性。方法 从培养的DC和胃癌细胞RNA冲击致敏DC的培养上清中分离exosome,观察其对胃癌的免疫治疗效果。结果 在用胃癌细胞RNA致敏DC分泌的exosomes对荷胃癌小鼠进行免疫治疗后,小鼠腹水产生率(50%)、肿瘤转移率(0%)、动物的存活率(100%)、平均瘤体质量(1.37±0.19)g等指标均优于对照组(P<0.05),局部IL-12、IL-18和IFNγ的基因表达显著增多(P<0.01),CD4~+、CD8~+细胞的数量明显增加(P<0.01),TIL细胞毒活性明显提高。结论 致敏exosomes可以强化胃癌局部的免疫功能,改善荷瘤宿主的生存质量。作为一种新型的治疗性疫苗,exosomes有着良好的研究价值和开发前景。
【Abstract】 Objective Dendritic cells(DCs) are the most potent of antigen-presenting cells. Our previous result unraveled the functional status of DC in the tissue of gastric cancer (GC) and precancerous lesions, and probed into the possibility of preventing solid carcinoma such as GC. Methods We extracted exosome, A certain DC-derived subcellular component, from DC transfected with RNA of murine GC cells, and observed the therapeutic efficiency of exosomes for mice canying GC by using exosomes. Results The indices such as the production rate of ascites of mice (50%), the metastasis rate of tumor (0%), the survival rate of animals (100%) and the average weight of tumor (1.37±0.19) g showed that the condition of the mice treated with sensitized DC-derived exosomes by RNA was superior to that of the control group (P<0.05), and the level of gene expression of local IL-12, IL-18 and IFNγ was significantly increased (P<0.01) and the amount of CD4~+, CD8~+ cells was remarkable raised (P<0.01) and the cytotoxicity of TIL was significantly enhanced. A certain therapeutic efficiency for mice carrying tumor can be realized. Conclusions DC-derived exosomes sensitized by RNA of gastric carcinoma cells can not only intensify the local immunologic function of GC but also make a better survival quality of the tumor-bearing host. Being a new type of therapeutic vaccine, exosomes is an important investigative value and a prospect of development.
- 【文献出处】 免疫学杂志 ,Immunological Journal , 编辑部邮箱 ,2003年05期
- 【分类号】R735.2
- 【被引频次】3
- 【下载频次】118