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木犀草素增强靶向 B7-H3 的双特异性 NK 细胞衔接器对非小细胞肺癌的抗肿瘤免疫

英文原题:Luteolin enhances antitumor immunity of B7-H3-targeted bispecific natural killer cell engagers against non-small cell lung cancer.

PubMed 2026/03/25(内容时间) Int J Biol Sci Q1 · IF 11.7(JCR 2025)

研究概要

非小细胞肺癌(NSCLC)是肺癌的主要形式,也是全球癌症相关死亡的主要原因,这主要归因于其侵袭性进展和对当前疗法的耐药性。

中文摘要

非小细胞肺癌(NSCLC)是肺癌的主要形式,也是全球癌症相关死亡的主要原因,这在很大程度上归因于其侵袭性进展和对当前疗法的耐药性。B7-H3已成为一个值得研究的新型免疫治疗靶点。木犀草素是一种在蔬菜和草药中大量存在的黄酮类多酚化合物,已在多种癌症类型中显示出显著的抗肿瘤作用。然而,其在NSCLC中的治疗作用机制仍知之甚少。本研究旨在探讨木犀草素与B7-H3靶向免疫治疗在NSCLC中的联合效应。结果表明,木犀草素以剂量依赖性方式抑制NSCLC细胞增殖,并与B7-H3抑制表现出增强的联合效应,同时还促进细胞凋亡。该联合策略在体外和体内均产生了显著的抑制作用。构建了一种靶向B7-H3的双特异性杀伤细胞衔接器(BiKE),并测量了抗体依赖性细胞介导的细胞毒性(ADCC)以评估其与木犀草素的联合效应。与单独使用木犀草素或BiKE相比,靶向B7-H3的BiKE与木犀草素联合时表现出更优的活性。我们的发现不仅将B7-H3确定为NSCLC的一个有前景的治疗靶点,还表明木犀草素可作为一种潜在的抗癌佐剂。本文提出的合理设计的联合策略可能会增强NSCLC的现有治疗模式。

展开英文摘要原文

Non-small-cell lung cancer (NSCLC) is the predominant form of lung cancer and the leading cause of cancer-related mortality worldwide, largely due to its aggressive progression and resistance to current therapies. B7-H3 has emerged as a novel immunotherapeutic target worthy of investigation. Luteolin, a flavonoid polyphenolic compound abundantly present in vegetables and herbs, has demonstrated significant anti-tumor effects in various cancer types. However, its therapeutic mechanism of action in NSCLC remains poorly understood. This study aimed to examine the combined effects of luteolin and B7-H3-targeted immunotherapy in NSCLC. The results demonstrated that luteolin suppressed NSCLC cell proliferation in a dose-dependent manner and exhibited enhanced combined effects with B7-H3 inhibition, while also promoting apoptosis. This combination strategy produced significant inhibitory effects both in vitro and in vivo . A B7-H3-targeted bispecific killer cell engager (BiKE) was constructed, and antibody-dependent cell-mediated cytotoxicity (ADCC) was measured to evaluate its combined effect with luteolin. The B7-H3-targeted BiKE showed superior activity when combined with luteolin compared to either treatment of luteolin or BiKE alone. Our findings not only identify B7-H3 as a promising therapeutic target for NSCLC but also suggest luteolin as a potential anticancer adjuvant. The rationally designed combination strategy presented here may enhance existing treatment paradigms for NSCLC.

论文信息

作者
Yang S、Zhang Z、He X、Ouyang Z、Tang S、Liang M、Chen Z、Liu Y
第一作者单位
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.China
通讯作者单位
Cancer Centre, Institute of Translational Medicine, Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.China
期刊
International journal of biological sciences2026
原文标识
PubMed 42003927 · DOI 10.7150/ijbs.125834