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Updated: Jun 10, 2025

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可编程细菌与PD-1阻断协同,以克服癌细胞内在的免疫抵抗机制
Fangda Li1, Zaofeng Yang1, Thomas M Savage1
1Department of Microbiology and Immunology, Columbia University, New York, NY, USA.
工程细菌将干扰素- (IFN-γ) 直接传递给瘤,增强抗瘤免疫力,克服对PD-1阻断等免疫治疗的抵抗,而不会产生毒性. 这种方法在治疗晚期癌症方面表现有前途.
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:
- 干扰素- (IFN-γ) 对于免疫治疗反应至关重要,但系统性输送会导致毒性.
- 癌细胞通过各种机制对免疫疗法产生抵抗力.
研究的目的:
- 为了工程益生菌细菌局部IFN-γ传递到瘤.
- 评估细菌衍生IFN-γ在克服免疫疗法耐药性的有效性和安全性.
主要方法:
- 工程化益生菌细菌以产生和释放内IFN-γ.
- 评估了细菌注射后的全身抗瘤免疫力和毒性.
- 研究了克服PD-1阻塞阻力的机制.
主要成果:
- 内注射IFN-γ产生细菌诱导了全身抗瘤免疫,没有毒性.
- 细菌衍生的IFN-γ激活了细胞毒性CD4+和CD8+T细胞,克服了原发性PD-1阻塞抵抗.
- 来自细菌的IFN-γ激活了NK细胞,克服了对PD-1封锁的获得性抵抗力.
结论:
- 产生IFN-γ的细菌是局部细胞因子递送的一个有希望的策略.
- 将细菌衍生IFN-γ与PD-1阻断相结合,可以克服晚期癌症的免疫疗法耐药性.
- 这种方法为局部晚期和转移性疾病提供了潜在的治疗策略.
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