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靶向 CD276:人舌鳞状细胞癌 CAR-NK 细胞免疫治疗的有前景策略

英文原题:Targeting CD276: a promising strategy for CAR-NK cell immunotherapy in human oral tongue squamous cell carcinoma.

查看英文原题

Targeting CD276: a promising strategy for CAR-NK cell immunotherapy in human oral tongue squamous cell carcinoma.

PubMed 2025/04/01(内容时间) BMC Cancer Q2 · IF 4.1(JCR 2025)

研究概要

人口腔舌鳞状细胞癌(OTSCC)是头颈部鳞状细胞癌(HNSCC)的一种常见类型,常确诊时已处于晚期且预后不良。

中文摘要

人类口腔舌鳞状细胞癌(OTSCC)是常见的头颈部鳞状细胞癌(HNSCC),患者确诊时常处于晚期且预后不良。手术、辅助放疗及放化疗等传统疗法治疗晚期 OTSCC 的疗效有限,凸显了开发创新治疗策略的迫切需求。生物信息学分析发现,CD276 是 OTSCC 的重要生物标志物;蛋白质高表达与晚期患者生存率显著降低相关。基于这一发现,研究者开发了来源于脐带血细胞(UCBC)、特异性靶向 CD276 的嵌合抗原受体自然杀伤(CAR-NK)细胞,旨在临床前研究中考察这一新型疗法对抗 OTSCC 的潜力。体外和离体研究显示,靶向 CD276 的 CAR-NK 细胞能够高效裂解 OTSCC 细胞系和原代细胞,并清除 OTSCC 类器官。这些有希望的结果突显 CD276 在 OTSCC 发病机制中的关键作用,并展示 CAR-NK 细胞疗法作为晚期 OTSCC 突破性治疗选择的潜力,为口腔医学转化研究带来新希望。

展开英文摘要原文

Human oral tongue squamous cell carcinoma (OTSCC) is a prevalent form of head and neck squamous cell carcinoma (HNSCC), often presenting at an advanced stage with a grim prognosis. Traditional therapeutic approaches such as surgery, adjuvant radiotherapy, and chemoradiotherapy have shown limited efficacy in treating advanced OTSCC, underscoring the urgent need for innovative treatment strategies. Our bioinformatics analysis identified CD276 as a significant biomarker in OTSCC, with high protein expression levels correlating to a markedly reduced survival rate in late-stage patients. This discovery has led us to develop chimeric antigen receptor-natural killer (CAR-NK) cells derived from umbilical cord blood cells (UCBCs), specifically targeting CD276. Our aim is to investigate this novel therapeutic approach for its potential to combat OTSCC under pre-clinical conditions. Our in vitro and ex vivo studies have demonstrated that CD276-targeted CAR-NK cells exhibit remarkable efficacy in lysing OTSCC cell lines and primary cells, as well as in eliminating OTSCC organoids. These promising results underscore the pivotal role of CD276 in OTSCC pathogenesis and highlight the potential of CAR-NK cell therapy as a groundbreaking treatment option for advanced-stage OTSCC, offering new hope for translational medicine in the field of stomatology.

论文信息

作者
Liu S、Guan T、Yang F、Zhang H、Yao Y、Huang J、Zhao P、Huang W
第一作者单位
Department of Oral and Maxillofacial Surgery, Xuchang Central Hospital, Xuchang, 461000, China.China
通讯作者单位
Department of Oral and Maxillofacial Surgery, Xuchang Central Hospital, Xuchang, 461000, China. xcszxyykqk@126.com.China
期刊
BMC cancer2025 Apr 1
原文标识
PubMed 40169956 · DOI 10.1186/s12885-025-13973-9