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EPHB4-CAR-T 细胞瘤内给药治疗口腔鳞状细胞癌的可行性

英文原题:Feasibility of Intratumoral Administration With EPHB4-CAR-T Cells for the Treatment of Oral Squamous Cell Carcinoma.

查看英文原题

Feasibility of Intratumoral Administration With EPHB4-CAR-T Cells for the Treatment of Oral Squamous Cell Carcinoma.

PubMed 2025/03/03(内容时间) Cancer Sci Q2 · IF 4.9(JCR 2025)

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中文摘要

口腔鳞状细胞癌(OSCC)是最常见的口腔癌类型,其预后仍然较差。在本研究中,我们发现几乎所有OSCC病例均显示高表达Ephrin B型受体4(EPHB4),且主要定位于肿瘤细胞膜上。

因此,EPHB4是嵌合抗原受体(CAR)T细胞治疗OSCC的潜在靶点。由于口腔可直接进入,局部给予CAR-T 细胞治疗OSCC是可行的。

在本研究中,我们利用异种移植模型研究了瘤内注射EPHB4特异性CAR-T 细胞对OSCC的疗效。为评估抗肿瘤效果,将SAS OSCC细胞系或OSCC患者来源异种移植(PDX)肿瘤皮下植入NOD SCID gamma小鼠,并将EPHB4-CAR-T 细胞瘤内注射两次。正如预期,给予CAR-T 细胞抑制了SAS细胞和PDX肿瘤的生长。CAR-T 细胞治疗使肿瘤组织中EPHB4表达减弱,并伴有肿瘤面积减小和CAR-T 细胞积聚。

我们的研究结果表明,瘤内注射EPHB4-CAR-T 细胞是OSCC的一种潜在治疗策略。

展开英文摘要原文

Oral squamous cell carcinoma (OSCC) represents the most common type of oral cancer, and its prognosis remains poor. In this study, we found that almost OSCC cases showed high Ephrin type-B receptor 4 (EPHB4) expression that was mainly localized on the membrane of tumor cells.

Therefore, EPHB4 represents a potential target of chimeric antigen receptor (CAR) T cell therapy for OSCC treatment. Because the oral cavity can be directly accessed, local administration of CAR-T cells is feasible for treating OSCC. In this study, we investigated the efficacy of intratumoral injection of EPHB4-specific CAR-T cells in OSCC using xenograft models.

To evaluate the anti-tumor effect, the SAS OSCC cell line or an OSCC patient-derived xenograft (PDX) tumor was subcutaneously implanted into NOD SCID gamma mice, and EPHB4-CAR-T cells were intratumorally injected twice. As expected, administration of CAR-T cells suppressed tumor growth of both SAS cells and PDX tumor. EPHB4 expression in tumor tissues was attenuated by CAR-T cell treatment, which was accompanied by a reduction in tumor area and accumulation of CAR-T cells.

Our findings suggest that intratumoral injection of EPHB4-CAR-T cells represents a potential therapeutic strategy for OSCC.

论文信息

作者
Ito Y、Suzuki T、Shimomura M、Takenouchi K、Ohnuki K、Shoda K、Kenmochi Y、Yagyu S
单位
Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.Japan
期刊
Cancer science2025 May
原文标识
PubMed 40029791 · DOI 10.1111/cas.70023