دورية أكاديمية
pHLIP-fused PD-L1 engages avelumab to elicit NK cytotoxicity under acidic conditions
| العنوان: | pHLIP-fused PD-L1 engages avelumab to elicit NK cytotoxicity under acidic conditions |
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| المؤلفون: | Junjuan Feng, Hang Zheng, Yuting Zhang, Haiyan Wu, Mianjing Wang, Ying Sun, Min Zhang, He Xiao, Chunxia Qiao, Jing Wang, Longlong Luo, Xinying Li, Jiannan Feng, Yanchun Shi, Yuanqiang Zheng, Yi Wang, Dongsheng Sheng, Guojiang Chen |
| المصدر: | Heliyon, Vol 10, Iss 9, Pp e30551- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Science (General) LCC:Social sciences (General) |
| مصطلحات موضوعية: | PD-L1, pHLIP, NK cell, Cytotoxicity, Acidic, Science (General), Q1-390, Social sciences (General), H1-99 |
| الوصف: | Natural killer (NK) cells represent key player in immune surveillance to eliminate transformed or malignant cells. One of mechanisms of action of NK cells is antibody-dependent cell-mediated cytotoxicity (ADCC) by recognizing tumor antigens on the surface of cancer cells. However, the heterogeneity of tumor antigens and the scarcity of membrane surface targets significantly restrict this strategy. Recently, we constructed a new cargo by tethering a low pH insertion peptide (pHLIP) to the C terminus of the ectodomain of programed death ligand-1 (PD-L1) and demonstrated its ability to modulate immune responses. Herein, the potential application of PD-L1-pHLIP in cancer therapy was determined. pHLIP tethering had no effect on the binding capacity of PD-L1 protein to an anti-PD-L1 antibody (i.e. avelumab). Association of pHLIP rendered PD-L1 segment display on the surface of cellular membrane in the acidic buffer instead of the neutral solution. Importantly, plate-coated or beads-coupled PD-L1-pHLIP enable robust activation and expression of cytotoxic mediators of NK cells via engaging avelumab. Overall, this work provides proof of concept that recombinant PD-L1 protein decorated on the cellular membrane driven by pHLIP in combination with appropriate monoclonal antibody has potentials to elicit NK cytotoxicity, which may represent a novel and promising therapeutic avenue in cancer. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2405-8440 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2405844024065824; https://doaj.org/toc/2405-8440 |
| DOI: | 10.1016/j.heliyon.2024.e30551 |
| URL الوصول: | https://doaj.org/article/556f7e1c3a3e424aa538a7cb4a2f75fd |
| رقم الأكسشن: | edsdoj.556f7e1c3a3e424aa538a7cb4a2f75fd |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 24058440 |
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| DOI: | 10.1016/j.heliyon.2024.e30551 |