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- doi: 10.1038/s43018-023-00668-y
- issn: 2662-1347
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info:eu-repo/semantics/altIdentifier/doi/10.1038/s43018-023-00668-y
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info:eu-repo/semantics/altIdentifier/pmid/37996514
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info:eu-repo/semantics/altIdentifier/eissn/2662-1347
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_4DE2DD03AF355
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
Keywords
Humans; Mice; Animals; Cytokines; Immunotherapy; Dendritic Cells; Neoplasms/therapy; Interleukin-12Similar subjects
Mouse House mice Mus musculus House mouseCite this document
A. Ghasemi et al., « Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy. », Serveur académique Lausannois, ID : 10.1038/s43018-023-00668-y
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Abstract
Dendritic cells (DCs) are antigen-presenting myeloid cells that regulate T cell activation, trafficking and function. Monocyte-derived DCs pulsed with tumor antigens have been tested extensively for therapeutic vaccination in cancer, with mixed clinical results. Here, we present a cell-therapy platform based on mouse or human DC progenitors (DCPs) engineered to produce two immunostimulatory cytokines, IL-12 and FLT3L. Cytokine-armed DCPs differentiated into conventional type-I DCs (cDC1) and suppressed tumor growth, including melanoma and autochthonous liver models, without the need for antigen loading or myeloablative host conditioning. Tumor response involved synergy between IL-12 and FLT3L and was associated with natural killer and T cell infiltration and activation, M1-like macrophage programming and ischemic tumor necrosis. Antitumor immunity was dependent on endogenous cDC1 expansion and interferon-γ signaling but did not require CD8 + T cell cytotoxicity. Cytokine-armed DCPs synergized effectively with anti-GD2 chimeric-antigen receptor (CAR) T cells in eradicating intracranial gliomas in mice, illustrating their potential in combination therapies.
