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MACSima 成像循环染色 (MICS) 技术揭示用于实体瘤 CAR-T 细胞治疗的组合靶点对

英文原题:MACSima imaging cyclic staining (MICS) technology reveals combinatorial target pairs for CAR T cell treatment of solid tumors.

PubMed 2022/02/03(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

研究概要

许多关键的研究进展利用了在单细胞水平上结合高分辨率与高内涵表征的技术。

中文摘要

许多关键的研究进展利用了在单细胞水平上结合高分辨率与高内涵表征的技术。我们引入了MICS(MACSima成像循环染色)技术,该技术能够在亚细胞分辨率下对单个样本中的数百个蛋白质靶标进行免疫荧光成像。MICS基于染色、成像和擦除的循环,利用重组抗体(REAfinity Antibodies)荧光标记的光漂白,或抗体(REAlease Antibodies)或其标记(REAdye_lease Antibodies)的释放。多标志物分析可以识别针对实体瘤免疫治疗的潜在靶标。利用MICS,我们分析了人胶质母细胞瘤、卵巢癌和胰腺癌以及16种健康组织,识别出EPCAM/THY1配对作为卵巢癌嵌合抗原受体(CAR)T细胞治疗的潜在靶标。使用Adapter CAR T细胞方法,我们展示了仅当两种标志物均表达时才选择性杀伤细胞。MICS代表了一种新的高内涵显微镜方法学,广泛适用于个性化医疗。

展开英文摘要原文

Many critical advances in research utilize techniques that combine high-resolution with high-content characterization at the single cell level. We introduce the MICS (MACSima Imaging Cyclic Staining) technology, which enables the immunofluorescent imaging of hundreds of protein targets across a single specimen at subcellular resolution. MICS is based on cycles of staining, imaging, and erasure, using photobleaching of fluorescent labels of recombinant antibodies (REAfinity Antibodies), or release of antibodies (REAlease Antibodies) or their labels (REAdye_lease Antibodies). Multimarker analysis can identify potential targets for immune therapy against solid tumors. With MICS we analysed human glioblastoma, ovarian and pancreatic carcinoma, and 16 healthy tissues, identifying the pair EPCAM/THY1 as a potential target for chimeric antigen receptor (CAR) T cell therapy for ovarian carcinoma. Using an Adapter CAR T cell approach, we show selective killing of cells only if both markers are expressed. MICS represents a new high-content microscopy methodology widely applicable for personalized medicine.

论文信息

作者
Kinkhabwala A、Herbel C、Pankratz J、Yushchenko DA、Rüberg S、Praveen P、Reiß S、Rodriguez FC
第一作者单位
Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.Germany
通讯作者单位
Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany. andreasbo@miltenyi.com.Germany
期刊
Scientific reports2022 Feb 3
原文标识
PubMed 35115587 · DOI 10.1038/s41598-022-05841-4