可编程的细菌与动态毒性调制系统用于精确的抗瘤免疫力
Leyang Wu1,2,3, Lin Li1, Liyuan Qiao1
1Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|July 26, 2024
概括
工程细菌提供癌症免疫疗法,但毒性是一个问题. 这项研究开发了一种新型的沙门氏菌株,它在健康的器官中是安全的,但精确地准瘤,增强抗瘤免疫力.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
背景情况:
- 工程细菌对癌症免疫疗法有希望,但面临的挑战是目标外毒性和有限的治疗窗口.
- 在瘤内可控制的微生物免疫性对于开发更安全的抗瘤应用至关重要.
研究的目的:
- 开发一种基因编码的微生物激活策略,使用可调节的细胞外多糖体表达来提高细菌生物相容性和疗效.
- 设计一种具有瘤特异性毒性和增强安全性的新型减弱型沙门氏菌株.
主要方法:
- 查沙门氏菌基因的巨细胞存活率,以确定减弱的底盘菌株 (AIS,htrA基因缺乏).
- 使用优化定量感知调控系统和合成基因电路 (HTRA-RCSA轴) 构建一个工程菌株 (AISI-H).
- 在黑色素瘤小鼠模型中评估细菌行为,瘤抑制和免疫激活.
主要成果:
- 该AIS菌株表现出高瘤丰富性和正常器官的快速清除.
- 该AISI-H菌株通过增加的细胞外多糖含量表现出动态的,瘤特异性的毒性.
- 在接受AISI-H治疗的小鼠中观察到显著的瘤抑制和强大的抗癌免疫激活.
- 该AISI-H菌株表现出极好的生物相容性,在正常器官中具有"关闭"活性,在瘤中具有"启动"活性.
结论:
- 开发的细菌调节策略提高了基于微生物的抗瘤剂的生物相容性和治疗疗效.
- 这种方法通过控制瘤内的细菌活动,为癌症免疫治疗提供了更安全,更精确的方法.
- 工程Salmonella菌株扩大了微生物治疗在瘤学的潜在应用.
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