肿瘤细胞治疗研究
英文原题:NF-κB/NFAT signaling contributes to B7-H3 TRuC-T cell cytotoxicity and supports a reporter platform for glioblastoma immunotherapy.
NF-κB/NFAT signaling contributes to B7-H3 TRuC-T cell cytotoxicity and supports a reporter platform for glioblastoma immunotherapy.
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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。
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。
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.
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