工程内共生生物调节主要巨细胞功能,通过转移瘤微环境来减轻瘤生长
Cody S Madsen1,2,3, Ashley V Makela2,3, Chima V Maduka2,4
1Nuclear and Chemical Sciences Division, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94550, United States.
ACS applied bio materials
|June 24, 2025
概括
工程细菌Bacillus subtilis作为内共生体来控制巨细胞的基因表达,以改善组织再生和癌症治疗. 这些工程细菌成功调节了免疫反应,并减弱了小鼠的瘤生长.
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:
- 调节巨细胞基因表达为组织再生和癌症治疗提供了潜力.
- 工程内共生生物 (EES) 可以居住在宿主细胞内,以控制巨细胞的功能.
研究的目的:
- 开发Bacillus subtilis作为一种用于调节巨细胞基因表达的EES.
- 评估EES在改变瘤微环境 (TME) 和治疗癌症方面的治疗潜力.
主要方法:
- 工程化B. subtilis分泌的listeriolysin O (LLO) 和转录因子 (TF).
- 使用巨/单细胞细胞系和来自小鼠骨髓的巨 (BMDMs) 的体外研究.
- 在体内研究,使用三阴性乳腺癌的 ортотоп性小鼠模型.
主要成果:
- EES调节的巨细胞表面标记物,细胞因子和化学因子.
- TF菌株改变了BMDM基因表达,细胞因子/化学因子产生和代谢模式.
- 在体内,TF菌株通过改变免疫细胞组成和减弱瘤生长来改变TME.
- 在小鼠中,多剂量TF菌株的耐受性很好.
结论:
- 作为EES的B. subtilis LLO TF菌株显示出通过细胞内免疫调节进行癌症免疫治疗的前景.
- EES技术可以扩展到针对哺乳动物细胞的各种生物医学应用.
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