Journal Article

DKFZ-2023-02449

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.

Ghasemi, A. ; Martinez-Usatorre, A. ; Li, L. ; Hicham, M. ; Guichard, A. ; Marcone, R. ; Fournier, N. ; Torchia, B. ; Martinez Bedoya, D. ; Davanture, S. ; Fernández-Vaquero, M. ; Fan, C.DKFZ* ; Janzen, J.DKFZ* ; Mohammadzadeh, Y. ; Genolet, R. ; Mansouri, N. ; Wenes, M. ; Migliorini, D. ; Heikenwälder, M.DKFZ* ; De Palma, M.

2024
Nature Research London

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Please use a persistent id in citations: doi:10.1038/s43018-023-00668-y

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.

Note: 2024 Feb;5(2):240-261

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Contributing Institute(s):

1. Chronische Entzündung und Krebs (F180)

Research Program(s):

1. 316 - Infektionen, Entzündung und Krebs (POF4-316) (POF4-316)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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