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姜黄素对 CAR-T 细胞治疗的免疫调节作用

英文原题:Immunomodulatory Effects of Curcumin on CAR T-Cell Therapy.

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Immunomodulatory Effects of Curcumin on CAR T-Cell Therapy.

PubMed 2025/04/10(内容时间) Antioxidants (Basel) Q1 · IF 8.2(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法改变了血液系统恶性肿瘤治疗,靶向并清除癌细胞的效力很高。然而,其临床应用可能伴随急性不良反应风险,包括由细胞因子过量产生引发的严重炎症反应——细胞因子释放综合征(CRS)。虽然已有抗细胞因子疗法用于管理CRS,仍需进一步策略在降低毒性的同时优化CAR-T 疗效。姜黄素是一种具有抗炎和抗氧化特性的生物活性多酚,有望作为CAR-T 疗法的辅助药物。本研究在体外评估姜黄素对抗CD19 CAR-T 细胞的影响。结果显示,姜黄素增强CAR-T 细胞对B细胞急性淋巴细胞白血病模型Nalm-6的细胞毒活性,同时降低IL-2和IFN-γ等促炎细胞因子的产生。为探究潜在机制,研究者开展网络药理学和分子对接分析,发现姜黄素可作用于参与T细胞活化及细胞因子调节的关键信号通路。这些发现支持姜黄素作为治疗辅助药物,有望提高CAR-T 疗效并减轻炎症毒性。

展开英文摘要原文

Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of hematological malignancies, demonstrating high efficacy in targeting and eliminating cancer cells.

However, its clinical application can be associated with the risk of acute adverse effects, including cytokine release syndrome (CRS), a severe inflammatory response caused by excessive cytokine production. While anti-cytokine therapies are available to manage CRS, additional strategies are needed to optimize CAR T-cell efficacy with reduced toxicities.

Curcumin, a bioactive polyphenol known for its anti-inflammatory and antioxidant properties, represents a promising adjunct for CAR T-cell therapy. In this study, we investigated the effects of curcumin on anti-CD19 CAR T-cells in vitro.

Our results show that curcumin enhances the cytotoxic activity of CAR T-cells against Nalm-6, a B-cell acute lymphoblastic leukemia model, while reducing the production of pro-inflammatory cytokines, including IL-2 and IFN- . To explore its underlying mechanisms, network pharmacology and molecular docking analyses were performed, which revealed that curcumin interacts with key signaling pathways involved in T-cell activation and cytokine regulation.

These findings support the potential of curcumin as a therapeutic adjunct to improve CAR T-cell efficacy while mitigating inflammatory toxicity.

论文信息

作者
Limsakul P、Srifa P、Huang Z、Zhu L、Wu Y、Charupanit K
第一作者单位
Division of Physical Science, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand.Thailand
通讯作者单位
Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.Thailand
期刊
Antioxidants (Basel, Switzerland)2025 Apr 10
原文标识
PubMed 40298832 · DOI 10.3390/antiox14040454