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控制T细胞-瘤细胞相互作用与癌症免疫治疗的生物模拟物理屏障

Yuxuan Zhang^1,2, Jinjin Wang^1,2, Guangchao Qing¹

¹Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

Proceedings of the National Academy of Sciences of the United States of America

|July 8, 2025

概括

一种新的生物模拟物理屏障 (BPB) 保护T细胞免受瘤相互作用的影响,防止疲劳并增强癌症免疫疗法. 这种受控的方法最大限度地提高T细胞的抗瘤活性,并促进持久的免疫记忆.

科学领域:

生物医学工程生物医学工程
免疫学免疫学免疫学
材料科学材料科学材料科学

背景情况:

癌症免疫疗法,特别是免疫检查点封锁,显示出希望,但由于T细胞耗尽,通常会产生暂时的疗效.
持续的T细胞与瘤相互作用加速T细胞的枯竭,限制了当前免疫疗法的耐用性.
需要策略来保护T细胞免受持续的瘤暴露,并保持其功能状态.

研究的目的:

开发一种基于水凝的仿生物理屏障 (BPB),在瘤微环境中为T细胞创造一个保护区.
暂时阻止T细胞与瘤细胞的相互作用,防止T细胞失活和枯竭.
调查BPB增强抗瘤免疫力的潜力,包括立即瘤回归,全身免疫激活和持久记忆反应.

主要方法:

制造一种基于水凝的仿生物理屏障 (BPB).
在现场部署BPB以创建T细胞和瘤细胞之间的临时物理屏障.
通过近红外光照射,通过凝-溶液过渡触发BPB拆解.
在瘤模型中评估T细胞积累,功能活性和抗瘤功效.

主要成果:

BPB成功创建了一个保护区,保护T细胞免受瘤诱导的疲劳,并促进它们的积累.
对BPB进行控制的拆解恢复了T细胞与瘤细胞的相互作用,使激活的T细胞能够攻击瘤细胞.
治疗BPB导致增强的立即瘤回归,全身免疫激活,以及长期保护瘤复发.
该方法证明有效控制多焦点瘤并诱导持久记忆反应.

结论:

仿生物理屏障 (BPB) 是一种有前途的策略,用于调节T细胞与瘤细胞在癌症免疫治疗中的相互作用.
BPB增强T细胞的持久性和功能,从而提高抗瘤功效和持久的免疫记忆.
这种创新方法具有巨大的潜力,可以通过克服T细胞枯竭来推进癌症免疫疗法.

关键词:

T细胞和瘤细胞的相互作用 T细胞耗尽的情况 T细胞保护区保护区生物模拟物理障碍 (BPB) 是一种物理障碍.癌症免疫疗法免疫疗法

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