Amplifying antigen-induced cellular responses with proximity labelling
文献类型：期刊论文
| 作者 | Li, Shuojun6; Men, Yinghui6,7; Wang, Zihan6; Wu, Yingcheng1,2,8,9; Sun, Hao6; Yin, Mingyang3; Fan, Xinrui6; Deng, Guiyun5; Yang, Zhicheng4; Yang, Tiange3 |
| 刊名 | NATURE
 |
| 出版日期 | 2025-09-10 |
| 页码 | 37 |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/s41586-025-09518-6 |
| 英文摘要 | Antigen-induced clustering of cell surface receptors, including T cell receptors and Fc receptors, represents a widespread mechanism in cell signalling activation1,2. However, most naturally occurring antigens, such as tumour-associated antigens, stimulate limited receptor clustering and on-target responses owing to insufficient density3, 4-5. Here we repurpose proximity labelling6, a method used to biotinylate and identify spatially proximal proteins, to amplify designed probes as synthetic antigen clusters on the cell surface. We develop an in vivo proximity-labelling technology controlled by either red light or ultrasound to covalently tag fluorescein probes at high density near a target antigen. Using T cell receptors as an example, we demonstrate that the amplified fluorescein effectively clusters and directs a fluorescein-binding bispecific T cell engager to induce enhanced T cell activation and cytotoxicity. Noninvasive, tissue-selective labelling in multiple syngeneic mouse tumour models produces potent immune responses that rapidly eradicate treated tumours. Efficient cell lysis further promotes epitope spreading to induce systemic immunity against untreated distal lesions and immune memory against rechallenge. Thus, proximity-labelling chemistry holds promise as a generalized strategy to manipulate antigen-dependent receptor function and cell states. |
| WOS关键词 | T-CELLS ; DENSITY ; IMMUNOTHERAPY ; INHIBITION ; RECEPTORS ; TOXICITY ; EFFICACY ; TARGET |
| 资助项目 | National Key R&D Program of China[2023YFA1801300] ; National Key R&D Program of China[2022YFA1304500] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB0570000] ; National Natural Science Foundation of China[92368102] ; National Natural Science Foundation of China[22377126] ; Shanghai Municipal Science and Technology Major Project ; National Science and Technology Major Project[92459301] ; SANS Investigator Award from Shanghai Academy of Natural Sciences |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001567761400001 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321480]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Gao, Qiang; Han, Shuo |
| 作者单位 | 1.Fudan Univ, Shanghai Acad Nat Sci, State Key Lab Genet & Dev Complex Phenotypes, Shanghai, Peoples R China 2.Fudan Univ, Human Phenome Inst, Shanghai Acad Nat Sci, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci,Key Lab Multicell Syst, Shanghai, Peoples R China 4.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Univ Chinese Acad Sci, Shanghai, Peoples R China 5.Huazhong Agr Univ, Coll Life Sci & Technol, Wuhan, Peoples R China 6.Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Key Lab RNA Innovat Sci & Engn, Ctr Excellence Mol Cell Sci,Chinese Acad Sci, Shanghai, Peoples R China 7.Shanghai Jiao Tong Univ, Med X Res Inst, Shanghai, Peoples R China 8.Zhongshan Hosp, Liver Canc Inst, Dept Hepatobiliary Surg & Transplantat, Key Lab Carcinogenesis, Shanghai, Peoples R China 9.Fudan Univ, Inst Biomed Sci, Shanghai Acad Nat Sci, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Shuojun,Men, Yinghui,Wang, Zihan,et al. Amplifying antigen-induced cellular responses with proximity labelling[J]. NATURE,2025:37. |
| APA | Li, Shuojun.,Men, Yinghui.,Wang, Zihan.,Wu, Yingcheng.,Sun, Hao.,...&Han, Shuo.(2025).Amplifying antigen-induced cellular responses with proximity labelling.NATURE,37. |
| MLA | Li, Shuojun,et al."Amplifying antigen-induced cellular responses with proximity labelling".NATURE (2025):37. |
入库方式： OAI收割
来源：上海药物研究所
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