非致病性大肠杆菌表现出抗诱的IL18突变蛋白增强了抗瘤和CAR NK细胞的反应
Shaobo Yang1,2, Michal Sheffer2, Isabel E Kaplan2
1Department of Bioengineering, Northeastern University, Boston, MA, USA.
Nature biotechnology
|October 4, 2024
概括
工程细菌将免疫增强型细胞因子直接传递给瘤,增强T和NK细胞的抗癌反应. 这种新型免疫疗法在对抗耐治疗固体瘤方面表现有前途.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 在瘤学瘤学.
背景情况:
- 瘤微环境可以通过损害免疫细胞功能和贩运来阻碍癌症治疗的有效性.
- 开发新的策略来克服这些抑制机制对于改善癌症治疗结果至关重要.
研究的目的:
- 为了设计非致病性大肠杆菌,向瘤提供免疫激活细胞因子.
- 在临床前癌症模型中评估这种基于细菌的免疫疗法的疗效.
主要方法:
- 在大肠杆菌K-12 DH5α上显示抗诱IL18蛋白 (DR18) 的表面显示.
- 在结直肠癌和黑色素瘤小鼠模型中评估免疫细胞激活 (CD8+ T细胞,NK细胞) 和抗瘤反应.
- 在抗NK细胞疗法耐药的间皮瘤异种移植模型中对工程化大肠杆菌的评估.
主要成果:
- 经过工程设计,表达小鼠DR18的大肠杆菌诱导了强大的CD8+ T和NK细胞反应,抑制了瘤的进展.
- 大肠杆菌显示人体DR18增强了准美索林的CAR NK细胞激活和瘤贩运.
- 通过促进TNF信号传递和NK细胞激活标志物,治疗延长了治疗耐药性间皮瘤模型中的生存期.
结论:
- 设计以显示细胞因子的活细菌代表了癌症免疫治疗的安全有效平台.
- 这种方法显示了诱导治疗耐药固体瘤中强有力的抗瘤反应的潜力.
- 需要对这种基于细菌的免疫治疗系统进行进一步的临床评估.
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