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工程细菌突破瘤的物理障碍,增强放射性免疫疗法

Yanxiang Zhang¹, Yue Liu¹, Tingting Li¹

¹State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, China.

Journal of controlled release : official journal of the Controlled Release Society

|August 3, 2024

概括

工程沙门氏菌分泌的纳托金酶 (NKase) 降低了瘤的物理障碍,通过促进免疫细胞透和防止瘤复发,提高了放射治疗的有效性.

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:

放射治疗激活抗瘤免疫力,但受到瘤微环境 (TME) 中的物理障碍所限制.
这些障碍物阻止免疫细胞的透,阻碍了瘤的完全消除.
现有的放射性免疫治疗策略需要加强,以克服TME的局限性.

研究的目的:

开发一种工程细菌来克服TME中的物理障碍.
通过改善免疫细胞透来提高放射治疗的疗效.
为了研究工程细菌和放射治疗对结肠瘤的协同作用.

主要方法:

开发了工程沙门氏菌分泌纳托金酶 (VNP^NKase) 的技术.
VNP^NKase被系统地用于结肠瘤模型.
分析了NKase对纤维素和细胞外基质 (ECM) 的降解.
评估了免疫细胞透 (CD103+树突细胞,CD8+T淋巴细胞) 和瘤根除.
在VNP^NKase预治疗和放射治疗后,评估了abscopal效应和免疫记忆.

主要成果:

在瘤部位选择性丰富的VNP^NKase.
NKase有效降解了纤维素和ECM,并使癌症相关纤维细胞 (CAF) 失活.
这种TME的重塑促进了树突细胞和CD8+T淋巴细胞的透.
在VNP^NKase前期治疗中,放大了abscopal效应,并建立了长期免疫记忆.
综合方法导致了局部瘤的具体根除和转移和复发的预防.

结论:

产生纳托金酶的工程细菌可以突破物理瘤屏障.
这一策略通过促进免疫细胞透来协同增强放射性免疫疗法.
这种方法在治疗固体瘤和预防转移和复发方面表现有前途.

关键词:

CD103 ((+) 树突细胞改造的细菌是一种工程细菌.放射性免疫疗法是一种放射性免疫疗法.瘤微环境是一个微环境.瘤的物理障碍是瘤的物理障碍.

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