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基于细菌的生物杂交物用于重塑腺介导免疫抑制以促进放射治疗触发的抗瘤免疫反应

Xirui Wu¹, Junjun Zhang², Zheng Deng¹

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, Soochow University, Suzhou 215123, China.

|December 14, 2024

概括

这项研究开发了一种基于细菌的疗法,将放射治疗与金属有机框架相结合,以增强抗瘤免疫力. 该疗法增强了免疫细胞死亡,并防止免疫抑制,有效地抑制瘤生长和转移.

科学领域:

生物医学工程生物医学工程
癌症免疫疗法癌症免疫疗法
纳米医学是一种纳米医学.

背景情况:

放射治疗 (RT) 诱导免疫细胞死亡 (ICD) 和ATP释放,激活抗瘤免疫力.
乙核酶CD39和CD73将ATP转化为免疫抑制性腺 (ADO),阻碍了RT的有效性.
开发克服ADO介导免疫抑制的策略对于提高RT结果至关重要.

研究的目的:

为增强RT诱导的ICD和抗瘤免疫力开发一种新的放射敏感剂平台.
为了抑制CD39的活性,并防止由腺介导的免疫抑制.
为了利用细菌载体进行向传递和免疫辅助作用.

主要方法:

在Escherichia coli Nissle 1917 (EcN) 上合成一个 (Bi) -酸 (EA) 金属有机框架 (MOF).
在MOF-EcN平台上加载CD39抑制剂聚氧胺 (POM-1).
在体外和体内评估该平台的放射敏感化,ICD诱导和免疫抑制阻断能力.

主要成果:

在RT时,MOF-EcN-POM-1平台显著增强了瘤细胞细胞毒性和ICD诱导.
POM-1有效地抑制了CD39,增加了细胞外ATP,并减少了免疫抑制的ADO.
EcN作为免疫辅助剂,促进树突细胞成熟和细胞毒性T淋巴细胞透.
结合疗法显示出强大的抑制已建立的瘤和显著的abscopal效应,减少转移.

结论:

这种基于细菌的生物混合系统有效地增强RT诱导的ICD,并维持抗瘤免疫力.
该策略克服了ADO介导的免疫抑制,为癌症治疗提供了一种有前途的方法.
该平台展示了通过联合免疫疗法和放射敏感化来改善固体瘤治疗结果的潜力.

关键词:

亚丁氨酸 (Adenosine) 是一种亚丁酸三酸盐是一种氨酸三酸盐.大肠杆菌 Escherichia coli 尼斯尔 1917 年辐射疗法辐射疗法多氧化的强化状态

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