A Synergistic Chemoimmunotherapy System Leveraging PD-L1 Blocking and Bioorthogonal Prodrug Activation
© 2024 Wiley‐VCH GmbH.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 30 vom: 02. Juli, Seite e2402322 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article bioorthogonal prodrug activation cancer‐targeting chemotherapy immunogenic cell death self‐reinforced tumor targeting tumor immune microenvironment Prodrugs B7-H1 Antigen Doxorubicin 80168379AG |
| Zusammenfassung: | © 2024 Wiley‐VCH GmbH. Novel strategies to facilitate tumor-specific drug delivery and restore immune attacks remain challenging in overcoming the current limitations of chemoimmunotherapy. An antitumor chemoimmunotherapy system comprising bioorthogonal reaction-ready group tetrazine (TZ) modified with an anti-PD-L1 antibody (αPD-L1TZ) and TZ-activatable prodrug vinyl ether-doxorubicin (DOX-VE) for self-reinforced anti-tumor chemoimmunotherapy is proposed. The αPD-L1TZ effectively disrupts the PD-L1/PD-1 interaction and activates the DOX prodrug in situ through the bioorthogonal click reaction of TZ and VE. Conversely, the activated DOX upregulates PD-L1 on the surface of tumor cells, facilitating tumor accumulation of αPD-L1TZ and enhancing DOX-VE activation. Furthermore, the activated DOX-induced immunogenic cell death of tumor cells, substantially improving the response efficiency of αPD-L1 in an immune-suppressive tumor microenvironment. Thus, PD-L1 blocking and bioorthogonal in situ prodrug activation synergistically enhance the antitumor efficacy of the chemoimmunotherapy system. Therefore, the system significantly enhances αPD-L1 tumor accumulation and prodrug activation and induces a robust immunological memory effect to prevent tumor recurrence and metastasis. Thus, a feasible chemoimmunotherapy combination regimen is presented |
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| Beschreibung: | Date Completed 25.07.2024 Date Revised 30.08.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202402322 |