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核散斑蛋白 SRRM2 暴露于癌细胞表面

英文原题:The Nuclear Speckles Protein SRRM2 Is Exposed on the Surface of Cancer Cells.

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The Nuclear Speckles Protein SRRM2 Is Exposed on the Surface of Cancer Cells.

PubMed 2024/09/17(内容时间) Cells Q2 · IF 6(JCR 2025)

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中文摘要

细胞外囊泡(EVs)的膜组成在很大程度上反映了其来源细胞的质膜组成。因此,我们假设EVs可用于免疫接种,以生成针对已知肿瘤抗原的单克隆抗体,但也可能针对迄今未知的肿瘤相关靶分子。通过一次免疫实验,我们获得了一种特异性针对SRRM2的单克隆抗体,SRRM2是一种参与剪接的RNA结合蛋白,也是核斑的主要成分。在此,我们使用该抗体证明SRRM2暴露于来自不同实体的多数癌细胞系表面,更重要的是,也暴露于体内癌细胞表面。此外,我们证明SRRM2特异性CAR-T 细胞在体外和体内均具有功能。总之,我们将SRRM2鉴定为一种暴露于癌细胞表面的有前景的新靶分子,并表明我们的SRRM2特异性抗体可作为开发新型靶向癌症疗法的基础。

展开英文摘要原文

The membrane composition of extracellular vesicles (EVs) largely reflects that of the plasma membrane of the cell of origin.

We therefore hypothesized that EVs could be used for immunizations to generate monoclonal antibodies against well-known tumor antigens but possibly also against hitherto unknown tumor-associated target molecules. From an immunization experiment, we obtained a monoclonal antibody specific for SRRM2, an RNA-binding protein involved in splicing and a major component of nuclear speckles.

Here, we used this antibody to demonstrate that SRRM2 is exposed on the surface of most cancer cell lines from various entities and, even more important, on cancer cells in vivo.

Moreover, we demonstrated that SRRM2-specific CAR-T cells are functional in vitro and in vivo. Collectively, we identified SRRM2 as a promising new target molecule exposed on the cancer cell surface and showed that our SRRM2-specific antibody can be used as a basis for the development of new targeted cancer therapies.

论文信息

作者
Kellner M、Hörmann J、Fackler S、Hu Y、Zhou T、Lu L、Ilik I、Aktas T
单位
Institute of Structural Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Feodor-Lynen-Str. 21, 81377 Munich, Germany.Germany
期刊
Cells2024 Sep 17
原文标识
PubMed 39329747 · DOI 10.3390/cells13181563