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采用T细胞转移和用冷凝支架的宿主抗原呈现细胞招募促进了对固体瘤的长期保护

Kwasi Adu-Berchie^1,2, Joshua M Brockman^1,2, Yutong Liu^1,2

¹John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.

Nature communications

|June 15, 2023

概括

这项研究引入了一种用于采用T细胞治疗的新型水凝,增强抗瘤免疫力. 这种方法可以改善长期的瘤控制,并通过激活宿主免疫细胞来防止瘤逃逸.

科学领域:

免疫学免疫学免疫学
生物材料科学生物材料科学
在瘤学瘤学.

背景情况:

采用T细胞疗法提供了立即的瘤解体,但受到有限的抗原识别和短期保护的影响.
提高T细胞疗法的疗效和耐用性仍然是癌症治疗的关键挑战.

研究的目的:

开发一种基于水凝的输送系统,用于增强局部免疫反应的采用性T细胞治疗.
提高T细胞治疗对固体瘤的长期疗效和保护能力.

主要方法:

一种水凝被设计为局部输送通过采用转移的T细胞到瘤部位.
这种水凝包含了粒细胞巨细胞殖民地刺激因子 (GMCSF) 和FMS类型的氨酸激酶3连接体 (FLT3L) 来招募宿主抗原呈现细胞 (APC).
包括CpG来激活宿主APC,而T细胞被装入局部的细胞存储库.

主要成果:

通过水凝库输送的T细胞显示,与直接周围内注射或静脉输注相比,对皮下B16-F10瘤的控制显著更好.
综合方法,结合T细胞输送与生物材料驱动的免疫细胞激活,延长T细胞激活.
这种方法最大限度地减少了宿主T细胞的耗尽,并实现了长期的瘤控制,即使瘤抗原逃逸.

结论:

这种基于水凝的新型输送系统通过招募和激活宿主免疫细胞,有效地增强了采用T细胞疗法.
综合方法既能提供立即的瘤解,又能持续长期保护对固体瘤.
这一策略有望克服当前T细胞疗法的局限性,包括瘤抗原逃逸.

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