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用于癌症免疫治疗的OX40L表达的M1类巨细胞外体

Yongkang Yu¹, Tingxuan Li², Meitong Ou²

¹State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, PR China; Tianjin Institutes of Health Science, Tianjin 301600, PR China; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen 518107, PR China.

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

|December 1, 2023

概括

工程设计的M1类巨细胞外体 (OX40L M1-exos) 协同增强先天性和适应性免疫力. 这种新的方法显示出强大的治疗效果,抑制了小鼠乳腺癌模型中的瘤生长和转移.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物技术是生物技术.

背景情况:

目前的免疫检查点抑制剂提供有限的临床益处.
在固体瘤中,T细胞介导的适应性免疫和巨细胞介导的先天性免疫都至关重要.
与瘤相关的巨细胞通常存在于一种免疫抑制的M2类状态.

研究的目的:

开发一种结合先天性和适应性免疫激活的新型治疗策略.
为癌症免疫疗法设计类似M1的巨细胞外体 (OX40L M1-exos).
在临床前癌症模型中评估OX40L M1-exos的治疗疗效.

主要方法:

开发设计的M1类巨细胞外体 (OX40L M1-exos).
评估OX40LM1-exos'能够激活OX40/OX40L通路的能力.
对M2型巨细胞重新编程成M1型巨细胞的评估.
在小鼠乳腺癌模型中测试治疗疗效,监测瘤生长和转移.

主要成果:

OX40L M1-exos通过OX40/OX40L通路成功激活了适应性免疫.
工程外体有效地将M2类巨细胞重新编程为M1类表型,恢复先天免疫力.
观察到先天性和适应性免疫之间的协同效应.
在小鼠模型中实现了显著的瘤生长和转移的抑制.

结论:

OX40L M1-exos代表了癌症的一个有前途的治疗策略.
这种方法有效地结合并增强了先天性和适应性免疫反应.
OX40L M1-exos可以作为现有的癌症免疫疗法的宝贵补充剂.

关键词:

工程外生体的工程外生体.巨细胞是一个巨细胞.OX40/OX40L 的时间.协同作用的先天免疫和适应性免疫.癌症免疫疗法免疫疗法

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