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通过增强抗瘤免疫力,工程化乳球球菌乳球菌的内治疗可促进恶性内液的回归

Yue Fan¹, Aoxing Chen², Junmeng Zhu³

¹The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China; The Clinical Cancer Institute of Nanjing University, Nanjing, China; The Comprehensive Cancer Centre, China Pharmaceutical University Nanjing Drum Tower Hospital, 321 Zhongshan Road, Nanjing, 210008, China.

|March 3, 2024

概括

在小鼠中,通过内输送的工程益生菌 (FOLactis) 有效治疗恶性内溢液 (MPE). 这种新型免疫疗法增强了抗瘤免疫力,为MPE管理提供了一个有前途的新策略.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
微生物学微生物学

背景情况:

恶性肺溢液 (MPE) 是癌症护理的一个重大挑战.
脑内免疫疗法,特别是基于细菌的方法,对MPE治疗有希望.
工程益生菌为有针对性的免疫刺激提供了一个潜在的平台.

研究的目的:

开发和评估一种用于治疗MPE的工程乳球菌 (FOLactis) 的内注射策略.
调查FOLactis介导的抗MPE效应背后的免疫机制.
评估内FOLactis与计划死亡1封锁的联合治疗.

主要方法:

工程化乳球菌乳糖 (FOLactis) 表达Fms类型的氨酸激酶3和OX40配体.
在MPE携带的小鼠模型中,内注射FOLactis.
免疫细胞群 (树突细胞,T细胞,NK细胞,巨细胞) 在瘤排水淋巴结中的流细胞测量分析.
评估MPE抑制,肺瘤负担和生存率.
结合疗法与抗编程死亡1抗体.

主要成果:

腹腔内FOLactis (I-Pl FOLactis) 显著抑制了MPE和腹腔瘤结节.
在MPE携带小鼠中,I-Pl FOLactis治疗显著延长了生存时间.
在瘤排水淋巴结中观察到CD103+树突细胞增加了三倍.
增强了效应记忆T细胞和CD8+T细胞的招募,NK细胞的激活和M1巨细胞的两极分化.
与抗PD-1抗体的联合治疗进一步改善了抗瘤疗效.

结论:

通过内注射的工程益生菌 (FOLactis) 代表了管理MPE的创新和有效策略.
这种方法通过调节树突细胞功能和促进效应体免疫细胞透来增强抗瘤免疫力.
FOLactis显示出良好的疗效和生物安全性,这表明MPE治疗中的临床转化潜力.

关键词:

改造的细菌是一种工程细菌.内注射内注射内注射恶性肺溢出恶性肺溢出恶性肺溢出瘤免疫疗法免疫疗法瘤微环境是一个微环境.

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