工程细菌的热反应激活,以触发微波除疗法后的抗瘤免疫力
Yumin Wu1, Bo Liu1, Yifan Yan1
1Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, 215123, Jiangsu, China.
Nature communications
|December 3, 2024
概括
工程细菌释放治疗性蛋白质,如IL-15和sPD-1,作为对微波除 (MWA) 热的反应. 这种方法增强了抗瘤免疫力,即使不完全去除瘤,也可以改善结果.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 生物技术是生物技术.
背景情况:
- 在微波切除 (MWA) 过程中不完全切除瘤可能导致瘤复发.
- 需要有效的辅助疗法来增强MWA的疗效和预防复发.
研究的目的:
- 为了设计Salmonella typhimurium VNP20009,以释放治疗性蛋白质,以应对MWA诱导的高温症.
- 评估这些工程细菌作为增强抗瘤免疫反应的辅助疗法的疗效.
主要方法:
- 在热控制下,工程VNP20009用于表达IL-15和IL-15受体α (IL-15&IL-15Rα) 或与可溶性编程细胞死亡蛋白1 (sPD-1) 共同表达IL-15&IL-15Rα.
- 在瘤中静脉注射工程细菌.
- 评估瘤殖民,MWA引发的治疗性蛋白质表达,以及随后的抗瘤免疫反应.
主要成果:
- 工程细菌 (15&15R@VNP) 成功殖民瘤,并在MWA上释放IL-15&IL-15Rα.
- 这种治疗引起了抗瘤免疫反应,即使在不完整的MWA后,也抑制了瘤生长.
- 同时表达的sPD-1 (sPD-1-15&15R@VNP) 通过逆转免疫细胞抑制和恢复耗尽的T细胞,进一步增强了疗效.
结论:
- 热响应工程细菌代表了一种有前途的战略,以增强MWA疗法.
- 这种方法有效地激活了抗瘤免疫力,为癌症治疗提供了一种新的辅助疗法.
- 工程细菌可以克服由PD-1/PD-L1轴介导的免疫抑制.
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