通过利用TRAIL诱导的细胞死亡和FLT3L免疫调节的工程化全基因干细胞介导的抗瘤免疫力
Thijs A van Schaik1, Kok-Siong Chen1, Nobuhiko Kanaya1
1Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
概括
可分泌的基于 TRAIL 的疗法可以杀死质母细胞瘤细胞,激活免疫细胞并改善存活率. 提供S-TRAIL和FLT3L的封装干细胞显示了对脑瘤的治疗潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物技术是生物技术.
背景情况:
- 质母细胞瘤 (GBM) 是一种高度恶性脑瘤.
- 针对死亡受体 (DR) 的疗法对GBM有希望.
- DR介导的细胞死亡对瘤免疫微环境 (TIME) 的影响尚不清楚.
研究的目的:
- 探索可分泌的人类瘤亡因子 (TNF) 相关的亡诱导配体 (S-TRAIL) 的免疫调节作用.
- 评估提供S-TRAIL和FMS类氨酸激酶3连接体 (FLT3L) 的全源干细胞 (SC) 的治疗潜力.
主要方法:
- 创建了同源性小鼠GBM模型 (免疫活性和抑制) 与仿真DR5.5.
- 开发了释放FLT3L和S-TRAIL的治疗性SCs.
- 在综合性和人性化GBM切除模型中评估封装SC-TRAIL/FLT3L的疗效.
主要成果:
- 在时间内S-TRAIL诱导了GBM细胞亡和树突细胞 (DC) 透和成熟.
- 封装SCs的移植在切除后改善了生存率和调高cDC1和CD8+T细胞.
- 封装的临床级的SCs显著减少了人性化小鼠的瘤体积.
结论:
- 在TIME中,S-TRAIL介导的细胞死亡起到免疫作用.
- 封装的基于细胞的治疗可以消除剩余的GBM细胞.
- 这种方法可以诱导长期的抗瘤免疫力.
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