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一种新的HVEM-Fc重组蛋白用于肺癌免疫疗法

Yuanshan Yao^1,2,3, Bin Li^2,3, Jing Wang¹

¹Department of Thoracic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, 200041, China.

Journal of experimental & clinical cancer research : CR

|February 20, 2025

概括

疹病毒进入媒介-Fc (HVEM-Fc) 通过刺激T细胞,有效抑制肺癌的生长和转移. 将HVEM-Fc与PD-1抑制剂结合起来显示出最强大的抗瘤效应.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
分子生物学分子生物学

背景情况:

疹病毒进入媒介 (HVEM) 是一种调节免疫反应的跨膜蛋白.
HVEM-Fc是一种新型的融合蛋白,旨在向瘤细胞.
作为免疫激活剂或抑制剂的HVEM的双重作用取决于连接体相互作用.

研究的目的:

评估HVEM-Fc在临床前肺癌模型中的抗瘤疗效.
研究HVEM-Fc抗癌活性背后的免疫机制.
评估HVEM-Fc与PD-1抑制剂结合的协同作用潜力.

主要方法:

在体内研究中,使用同基因和正基因小鼠肺癌模型.
在体外验证使用患者衍生的非小细胞肺癌 (NSCLC) 器官和T细胞共同培养.
多omics分析包括单细胞RNA测序,空间转录组学和流细胞计.
用编程死亡-1 (PD-1) 抑制剂和免疫细胞耗尽研究对联合治疗的评估.

主要成果:

在小鼠模型中,HVEM-Fc在1mg/kg的剂量下显著抑制了瘤生长和转移.
多omics数据显示,HVEM-Fc促进了一个免疫刺激性瘤微环境.
将HVEM-Fc与PD-1抑制剂结合,实现了最强大的瘤细胞生长抑制.
试验室模型证实了HVEM-Fc通过T细胞激活来根除瘤细胞的能力.

结论:

在小鼠和人类NSCLC模型中,HVEM-Fc显著增加和延长T细胞活性.
与HVEM-Fc和PD-1抑制剂的联合治疗提供了优异的抗瘤结果.
在肺癌治疗中,HVEM-Fc 是一个有前途的治疗剂.

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