基于RNA的合成免疫调节基因电路用于癌症免疫治疗
Lior Nissim1, Ming-Ru Wu1, Erez Pery1
1Synthetic Biology Group, Research Laboratory of Electronics , Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell
|October 24, 2017
概括
这项研究引入了用于癌症免疫治疗的新基因循环,使得瘤特异性免疫刺激分子的表达成为可能. 这种方法可以提高癌细胞的杀死力,同时减少对健康细胞的伤害,
科学领域:
- 生物技术
- 免疫学
- 合成生物学
背景情况:
- 癌症免疫疗法面临的挑战包括罕见的瘤抗原,免疫抑制和全身毒性.
- 目前的免疫疗法需要特定的瘤抗原,
研究的目的:
- 开发一种用于瘤特异性免疫刺激的概念验证免疫调节基因电路.
- 通过提高特异性和降低毒性来克服当前癌症免疫疗法的局限性.
主要方法:
- 设计合成癌症特异性促进剂和基于RNA的AND门用于组合控制.
- 设计基因电路以表达免疫蛋白,细胞因子,化学因子和检查点抑制剂抗体.
- 在瘤细胞杀死和瘤减少方面评估了循环疗效.
主要成果:
- 通过T细胞选择性杀死癌细胞,在体外保存正常细胞.
- 在体内通过lentiviral基因循环实现显著的瘤减少和 prolonged小鼠存活.
- 验证了AND门的组合输出,以精确激活免疫反应.
结论:
- 开发的基因电路平台显示了向癌症免疫治疗的潜力.
- 这种方法为克服当前癌症治疗的主要局限性提供了一种策略.
- 该平台可适应各种免疫调节剂,癌症类型和其他需要免疫编程的疾病.
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