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一种用于分析细胞间相互作用并增强靶向肿瘤免疫治疗的通用化学酶标记系统

英文原题:A universal chemoenzymatic labeling system for profiling cell-cell interactions and potentiating targeted tumor immunotherapy.

查看英文原题

A universal chemoenzymatic labeling system for profiling cell-cell interactions and potentiating targeted tumor immunotherapy.

PubMed 2026/05/13(内容时间) Mol Ther Q1 · IF 11.4(JCR 2025)

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中文摘要

细胞膜上的分子决定了细胞如何与其环境及其他细胞相互作用,并作为肿瘤免疫治疗的靶点。酶催化的邻近标记已成为研究细胞间通讯和功能化细胞膜的关键工具。为了实现更精确、高效的细胞膜工程酶标记,进一步研究新型标记策略至关重要。

在本研究中,我们开发了一种利用 SrtA-SpA C 的精确化学酶标记策略,由抗体介导(Ab-SS),作为检测细胞-细胞相互作用和构建用于肿瘤免疫治疗的抗体-细胞偶联物(ACCs)的通用方法。首先,我们成功采用 Ab-SS 策略在复杂细胞环境中标记特定细胞群体。

此外,该方法可精确扩展至标记与靶细胞相互作用的细胞群。利用 Ab-SS 系统,我们报道了一种有效的 ACC 平台,作为嵌合抗原受体技术的替代方案。该平台精确地将肿瘤靶向抗体装备到免疫细胞上,以引导其识别和攻击癌细胞。

总之,鉴于其灵活性和强大功能,Ab-SS 酶标记系统提供了一种通用策略,通过邻近标记促进细胞功能研究并推进靶向免疫细胞治疗。

展开英文摘要原文

Molecules on the cell membrane dictate how cells interact with their environment and other cells and serve as the target for tumor immunotherapy. Enzyme-catalyzed proximity labeling has become a pivotal tool for studying intercellular communication and functionalizing cell membranes. To enable more precise and efficient enzymatic labeling for cell membrane engineering, further investigation of novel labeling strategies is crucial.

In this study, we developed a precise chemoenzymatic labeling strategy using SrtA-SpA C , mediated by antibodies (Ab-SS), as a general method for detecting cell-cell interactions and constructing antibody-cell conjugates (ACCs) for tumor immunotherapy. Firstly, we successfully employed the Ab-SS strategy to label specific cell populations within complex cellular environments.

Furthermore, this method can be precisely extended to label cell groups that interact with the target cells. Employing the Ab-SS system, we report a potent ACC platform as an alternative to chimeric antigen receptor technology. This platform precisely equips immune cells with tumor-targeting antibodies to direct their recognition and attack against cancer cells.

Collectively, given its flexibility and robust functionality, the Ab-SS enzymatic labeling system provides a generalized strategy for facilitating research on cellular function and advancing targeted immune cell therapies through proximity labeling.

论文信息

作者
Zhou H、Yang LT、Zhang X、Li S、Zhu JM、Chen KM、Duan CW
第一作者单位
Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.China
通讯作者单位
Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Fujian Branch of Shanghai Children's Medical Center Affiliated to SJTU-SM, Fujian Children's Hospital, Fuzhou, Fujian 350005, China; Clinicopathological Diagnosis & Research Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China. Electronic address: caiwenduan@sjtu.edu.cn.China
期刊
Molecular therapy : the journal of the American Society of Gene Therapy2026 Jun 3
原文标识
PubMed 42130087 · DOI 10.1016/j.ymthe.2026.05.005