工程Proteus mirabilis通过增强细胞毒性T细胞反应来提高抗瘤疗效
Hong Zhang1,2, Yinlin Luo1, Xincheng Zhao3
1Institute of Tropical Agriculture and Forestry, Hainan University, Haikou, Hainan 570228, P.R. China.
Molecular therapy. Oncology
|April 10, 2024
概括
经过工程设计的表达Vibrio vulnificus flagellin B (FlaB) 的Proteus mirabilis有效地殖民瘤,增强了抗癌免疫力,并抑制了小鼠的瘤生长. 这种细菌对新型癌症免疫治疗策略有前途.
科学领域:
- 细菌学 细菌学是一门学科.
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 细菌癌症免疫疗法利用生物工程细菌来增强抗癌免疫反应.
- 奇迹性蛋白质因其在抗瘤疗法中的潜力而未被充分探索.
研究的目的:
- 为了研究转基因工程 Proteus mirabilis 过度表达 Vibrio vulnificus 鞭 B (FlaB) 的抗瘤功效.
- 在小鼠瘤模型中评估FlaB表达P.mirabilis的安全性和免疫调节效应.
主要方法:
- 在P. mirabilis的基因工程中表达V. vulnificus FlaB.
- 给CT26瘤携带的小鼠注射工程细菌.
- 分析瘤殖民,免疫细胞透,细胞因子/细胞毒性蛋白质分泌和瘤生长.
- 评估PD-L1表达和与PD-L1阻断的联合治疗.
- 监测血清肝脏生物化学指数用于毒性评估.
主要成果:
- 表达FlaB的P. mirabilis成功地殖民了瘤组织,并显著抑制了瘤的生长.
- 治疗增强了T细胞透和瘤内的细胞因子和细胞毒性蛋白质的分泌.
- 在瘤透免疫细胞中观察到升高的编程死亡配体1 (PD-L1) 表达.
- 结合治疗与FlaB表达P.奇迹菌和PD-L1阻断协同增强了抗瘤效应.
- FlaB表达没有增加P.奇迹菌的体内毒性,肝酶的过渡性升高随着时间的推移而恢复.
结论:
- 工程设计的P. mirabilis过度表达FlaB显示出显著的抗瘤潜力.
- 这种方法通过免疫细胞透和细胞因子调节来增强抗癌免疫力.
- 奇迹菌 (P. mirabilis) 作为一种可行的平台,用于开发基于细菌的癌症免疫疗法.
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