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编造的TCR-T细胞分泌IFNα/Anti-PD-L1可增强内源免疫力,以协同增强对固体瘤的有效性

Yuan Sun¹, Xuan Che¹, Xiya Wang¹

¹Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China.

Molecular therapy : the journal of the American Society of Gene Therapy

|February 25, 2026

概括

固体瘤的工程T细胞疗法通过分泌干扰素α (IFNα) 和抗PD-L1.1得到改善. 这种双重向的方法可以增强T细胞的功能,并动员免疫系统进行有效的瘤根除.

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:

T细胞受体工程T细胞 (TCR-T) 疗法对固体瘤具有前景,但面临的挑战包括T细胞功能障碍和抑制的瘤微环境.
干扰素α (IFNα) 可以改善瘤微环境,但系统性输送会对瘤细胞产生不良影响和PD-L1上调.

研究的目的:

开发一种新的TCR-T细胞疗法,克服目前固体瘤治疗方法的局限性.
通过改善瘤微环境和内源性免疫激活来提高TCR-T细胞疗法的疗效和安全性.

主要方法:

查细胞因子以确定瘤微环境的关键调节者,从而选择IFNα.
工程TCR-T细胞分泌IFNα和抗PD-L1抗体,用于双瘤向.
评估IFNα和抗PD-L1对T细胞功能,瘤微环境调节和内源性免疫细胞激活的协同作用.

主要成果:

工程TCR-T细胞分泌IFNα/anti-PD-L1证明了双重向,提高了安全性和有效性.
工程T细胞通过阻断PD-L1,促进Th1分化,刺激NK细胞细胞毒性和促进树突细胞成熟来增强瘤微环境.
这种方法导致了在临床前模型中有效和安全地根除固体瘤.

结论:

一种新型的TCR-T细胞疗法分泌IFNα/anti-PD-L1,提供了一种协同策略,以增强T细胞功能并克服瘤微环境障碍.
这种方法有效地调动内源性免疫细胞,从而产生强大的抗瘤活性,并具有在固体瘤治疗中临床转换的重大潜力.

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