Self-Blockade of PD-L1 with Bacteria-Derived Outer-Membrane Vesicle for Enhanced Cancer Immunotherapy
© 2022 Wiley-VCH GmbH.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 34(2022), 7 vom: 27. Feb., Seite e2106307 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2022
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article immune checkpoint immune response immunotherapy nanocarriers outer-membrane vesicles B7-H1 Antigen CD274 protein, human |
| Zusammenfassung: | © 2022 Wiley-VCH GmbH. The checkpoint inhibitor therapy that blocks programmed death-1 (PD-1) and its major ligand PD-L1 has achieved encouraging clinical efficacy in certain cancers. However, the binding of checkpoint inhibitors with other immune cells that express PD-L1 often results in a low response rate to the blockade and severe adverse effects. Herein, an LyP1 polypeptide-modified outer-membrane vesicle (LOMV) loaded with a PD-1 plasmid is developed to achieve self-blockade of PD-L1 in tumor cells. The nanocarriers accumulate in the tumor tissue through OMV-targeting ability and are internalized into the tumor cells via the LyP1-mediated target, subsequently delivering PD-1 plasmid into the nucleus, leading to the expression of PD-1 by the tumor cells. In addition, a magnetic particle chemiluminescence kit is developed to quantitatively detect the binding rate of PD-1/PD-L1. The self-expressed PD-1 bonded with the PD-L1 is expressed by both autologous and neighboring tumor cells, achieving self-blockade. Simultaneously, the outer-membrane protein of LOMV recruits cytotoxic lymphocyte cells and natural killer cells to tumor tissues and stimulates them to secrete IFN-γ , improving the antitumor activity of the PD-1/PD-L1 self-blocking therapy |
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| Beschreibung: | Date Completed 31.03.2022 Date Revised 14.07.2022 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202106307 |