%0 Journal Article
%A Ghasemi, Ali
%A Martinez-Usatorre, Amaia
%A Li, Luqing
%A Hicham, Mehdi
%A Guichard, Alan
%A Marcone, Rachel
%A Fournier, Nadine
%A Torchia, Bruno
%A Martinez Bedoya, Darel
%A Davanture, Suzel
%A Fernández-Vaquero, Mirian
%A Fan, Chaofan
%A Janzen, Jakob
%A Mohammadzadeh, Yahya
%A Genolet, Raphael
%A Mansouri, Nahal
%A Wenes, Mathias
%A Migliorini, Denis
%A Heikenwälder, Mathias
%A De Palma, Michele
%T Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.
%J Nature cancer
%V 5
%N 2
%@ 2662-1347
%C London
%I Nature Research
%M DKFZ-2023-02449
%P 240-261
%D 2024
%Z 2024 Feb;5(2):240-261
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37996514
%R 10.1038/s43018-023-00668-y
%U https://inrepo02.dkfz.de/record/285587