Nanocomplex-Mediated In Vivo Programming to Chimeric Antigen Receptor-M1 Macrophages for Cancer Therapy
© 2021 Wiley-VCH GmbH.
Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 33(2021), 43 vom: 05. Okt., Seite e2103258 |
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Weitere Verfasser: | , , , , , , , , , , , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2021
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Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
Schlagworte: | Journal Article CAR-macrophage DNA/polymer nanocomplex cancer therapy cytotoxic T lymphocyte in situ transfection Receptors, Chimeric Antigen Interferon-gamma 82115-62-6 |
Zusammenfassung: | © 2021 Wiley-VCH GmbH. Chimeric antigen receptor-T (CAR-T) cell immunotherapy has shown impressive clinical outcomes for hematologic malignancies. However, its broader applications are challenged due to its complex ex vivo cell-manufacturing procedures and low therapeutic efficacy against solid tumors. The limited therapeutic effects are partially due to limited CAR-T cell infiltration to solid tumors and inactivation of CAR-T cells by the immunosuppressive tumor microenvironment. Here, a facile approach is presented to in vivo program macrophages, which can intrinsically penetrate solid tumors, into CAR-M1 macrophages displaying enhanced cancer-directed phagocytosis and anti-tumor activity. In vivo injected nanocomplexes of macrophage-targeting nanocarriers and CAR-interferon-γ-encoding plasmid DNA induce CAR-M1 macrophages that are capable of CAR-mediated cancer phagocytosis, anti-tumor immunomodulation, and inhibition of solid tumor growth. Together, this study describes an off-the-shelf CAR-macrophage therapy that is effective for solid tumors and avoids the complex and costly processes of ex vivo CAR-cell manufacturing |
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Beschreibung: | Date Completed 24.07.2024 Date Revised 26.08.2024 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-4095 |
DOI: | 10.1002/adma.202103258 |