Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.

Autor: Ghasemi A; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland., Martinez-Usatorre A; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland., Li L; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland., Hicham M; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland., Guichard A; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland., Marcone R; Agora Cancer Research Center, Lausanne, Switzerland.; Translational Data Science (TDS) Facility, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland., Fournier N; Agora Cancer Research Center, Lausanne, Switzerland.; Translational Data Science (TDS) Facility, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland., Torchia B; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland., Martinez Bedoya D; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland.; Center for Translational Research in Onco-Hematology, University of Geneva (UNIGE), Geneva, Switzerland., Davanture S; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland.; Center for Translational Research in Onco-Hematology, University of Geneva (UNIGE), Geneva, Switzerland., Fernández-Vaquero M; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Fan C; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Janzen J; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Mohammadzadeh Y; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland., Genolet R; Ludwig Institute for Cancer Research, Lausanne, Switzerland.; Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland., Mansouri N; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland., Wenes M; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland.; Center for Translational Research in Onco-Hematology, University of Geneva (UNIGE), Geneva, Switzerland., Migliorini D; Agora Cancer Research Center, Lausanne, Switzerland.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland.; Center for Translational Research in Onco-Hematology, University of Geneva (UNIGE), Geneva, Switzerland.; Department of Oncology, Geneva University Hospital (HUG), Geneva, Switzerland., Heikenwalder M; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.; The M3 Research Center, Eberhard Karls University, Tübingen, Germany.; Cluster of Excellence iFIT (EXC 2180), Eberhard Karls University, Tübingen, Germany., De Palma M; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland. michele.depalma@epfl.ch.; Agora Cancer Research Center, Lausanne, Switzerland. michele.depalma@epfl.ch.; Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland. michele.depalma@epfl.ch.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2024 Feb; Vol. 5 (2), pp. 240-261. Date of Electronic Publication: 2023 Nov 23.
DOI: 10.1038/s43018-023-00668-y
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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