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NF-κB/NFAT 信号通路促进 B7-H3 TRuC-T 细胞细胞毒性并支持胶质母细胞瘤免疫治疗的报告平台

英文原题:NF-κB/NFAT signaling contributes to B7-H3 TRuC-T cell cytotoxicity and supports a reporter platform for glioblastoma immunotherapy.

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NF-κB/NFAT signaling contributes to B7-H3 TRuC-T cell cytotoxicity and supports a reporter platform for glioblastoma immunotherapy.

PubMed 2026/07/30(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

在与 B7-H3 结合后,NFAT 和 NF-κB 信号通路均被激活,并参与调控靶向 B7-H3 的 TRuC-T 细胞。我们的数据表明,整合到这些 TRuC 构建体中的 NF-κB/NFAT 转录报告基因可用于监测靶标识别,并可能作为细胞毒性疗效的早期指标。总体而言,该系统提示了 GBM 治疗的一条潜在途径,并为 TRuC-T 细胞治疗效力的功能评估提供了初步框架。

研究思路结论见上方概要

胶质母细胞瘤(GBM)是神经系统最常见且最具侵袭性的恶性肿瘤,因其进展迅速、预后极差,构成严峻的临床挑战。T细胞受体融合构建体(TRuC)-T细胞是超越CAR-T 技术的一种极具前景的工程化T细胞疗法。早期预测TRuC-T细胞对GBM的细胞毒性对于临床应用至关重要。

我们开发了靶向B7-H3的TRuC-T细胞,并将NF-κB或NFAT响应转录元件整合到TRuC构建体中。通过流式细胞术、荧光素酶试验以及体外/体内功能研究,我们评估了TRuC-T细胞是否通过NF-κB和NFAT信号通路发挥细胞毒性作用。

B7-H3 TRuC-T细胞在体外和体内均有效抑制了GBM生长。携带NF-κB或NFAT报告基因的TRuC-T细胞与靶细胞共培养后诱导了GFP表达,表明信号通路被激活。

展开英文摘要原文

We developed B7-H3-targeting TRuC-T cells and incorporated NF- B- or NFAT-responsive transcriptional elements into the TRuC construct. Using flow cytometry, luciferase assays, and in vitro / vivo functional studies, we evaluated whether TRuC-T cells exert cytotoxicity via NF- B and NFAT signaling pathways.

B7-H3 TRuC-T cells effectively suppressed GBM growth both in vitro and in vivo . Co-culture of TRuC-T cells carrying NF- B- or NFAT-reporters with target cells induced GFP expression, indicating pathway activation. DISCUSSION: Upon engagement with B7-H3, both NFAT and NF- B signaling pathways are activated and participate in the regulation of B7-H3-targeting TRuC-T cells. Our data demonstrate that NF- B/NFAT transcriptional reporters integrated into these TRuC constructs can be utilized to monitor target recognition and may serve as early indicators of cytotoxic efficacy. Overall, this system suggests a potential avenue for GBM therapy and offers an initial framework for the functional assessment of TRuC-T cell therapeutic potency.

论文信息

作者
Lin J、Zhang P、Li X、Lu S、Yu Q、Zheng J、Yang J、Chen X
第一作者单位
Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.China
通讯作者单位
Department of Geriatric, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.China
期刊
Frontiers in immunology2026
原文标识
PubMed 42597823 · DOI 10.3389/fimmu.2026.1876463