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000285587 1001_ $$aGhasemi, Ali$$b0
000285587 245__ $$aCytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.
000285587 260__ $$aLondon$$bNature Research$$c2024
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000285587 520__ $$aDendritic cells (DCs) are antigen-presenting myeloid cells that regulate T cell activation, trafficking and function. Monocyte-derived DCs pulsed with tumor antigens have been tested extensively for therapeutic vaccination in cancer, with mixed clinical results. Here, we present a cell-therapy platform based on mouse or human DC progenitors (DCPs) engineered to produce two immunostimulatory cytokines, IL-12 and FLT3L. Cytokine-armed DCPs differentiated into conventional type-I DCs (cDC1) and suppressed tumor growth, including melanoma and autochthonous liver models, without the need for antigen loading or myeloablative host conditioning. Tumor response involved synergy between IL-12 and FLT3L and was associated with natural killer and T cell infiltration and activation, M1-like macrophage programming and ischemic tumor necrosis. Antitumor immunity was dependent on endogenous cDC1 expansion and interferon-γ signaling but did not require CD8+ T cell cytotoxicity. Cytokine-armed DCPs synergized effectively with anti-GD2 chimeric-antigen receptor (CAR) T cells in eradicating intracranial gliomas in mice, illustrating their potential in combination therapies.
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000285587 7001_ $$00000-0002-3416-1529$$aMartinez-Usatorre, Amaia$$b1
000285587 7001_ $$aLi, Luqing$$b2
000285587 7001_ $$00000-0002-9979-4757$$aHicham, Mehdi$$b3
000285587 7001_ $$00000-0001-8623-9570$$aGuichard, Alan$$b4
000285587 7001_ $$aMarcone, Rachel$$b5
000285587 7001_ $$00000-0002-9347-7929$$aFournier, Nadine$$b6
000285587 7001_ $$aTorchia, Bruno$$b7
000285587 7001_ $$00000-0002-1603-5801$$aMartinez Bedoya, Darel$$b8
000285587 7001_ $$aDavanture, Suzel$$b9
000285587 7001_ $$aFernández-Vaquero, Mirian$$b10
000285587 7001_ $$0P:(DE-He78)0bf6ca3fa56c2f2b5454e23b0fb14054$$aFan, Chaofan$$b11$$udkfz
000285587 7001_ $$0P:(DE-He78)c84e05a07a8f652e3a0be63323ded958$$aJanzen, Jakob$$b12$$udkfz
000285587 7001_ $$aMohammadzadeh, Yahya$$b13
000285587 7001_ $$aGenolet, Raphael$$b14
000285587 7001_ $$aMansouri, Nahal$$b15
000285587 7001_ $$00000-0001-8478-8592$$aWenes, Mathias$$b16
000285587 7001_ $$00000-0003-0151-3222$$aMigliorini, Denis$$b17
000285587 7001_ $$0P:(DE-He78)66ed2d4ec9bc11d29b87ac006adf85e5$$aHeikenwälder, Mathias$$b18$$udkfz
000285587 7001_ $$00000-0001-9128-5459$$aDe Palma, Michele$$b19
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