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用工程细菌对瘤进行代谢调节以用于免疫治疗
Fernando P Canale1, Camilla Basso1,2, Gaia Antonini1
1Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
Nature
|October 7, 2021
概括
通过在瘤中将氨酸转化为L-氨酸来增强抗瘤T细胞反应. 这种方法提高了免疫检查点抑制剂的疗效,为癌症免疫治疗提供了一种新的策略.
科学领域:
- 免疫学
- 微生物学
- 合成生物学
背景情况:
- 对于有效的抗瘤T细胞反应来说,L- 氨酸的可用性至关重要.
- 低瘤内L-阿尔金因度限制了PD-L1阻断抗体等免疫疗法的有效性.
- 目前缺乏增加瘤内L-氨酸的方法.
研究的目的:
- 开发一种局部增加瘤内L-氨酸水平的方法.
- 设计一种益生菌用于瘤殖民和L-氨酸的生产.
- 评估工程细菌与PD-L1阻断结合的治疗潜力.
主要方法:
- 通过合成生物学来设计大肠杆菌Nissle 1917.
- 工程细菌被设计成将瘤积累的氨转化为L-氨.
- 通过工程细菌对瘤的殖民化和随后的免疫反应进行了评估.
主要成果:
- 工程细菌成功地殖民瘤并增加了瘤内L-氨酸度.
- 增加的L- 氨酸水平导致瘤透T细胞数量增加.
- 使用工程细菌和PD- L1抗体的联合治疗显示出协同的瘤清除.
结论:
- 工程微生物疗法可以在代谢上调节瘤微环境.
- 这种方法提高了癌症免疫疗法的疗效.
- 抗瘤作用由L-阿尔金因介导,并依赖于T细胞.
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