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Scientific article
Open access
English

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

Published inNature cancer
First online date2023-11-23
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.

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Funding
  • European Commission - Extracellular Vesicle-Internalizing Receptors (EVIRs) for Cancer ImmunoGeneTherapy [725051]
  • European Commission - Cellular and molecular mechanisms of metabolic immune activation triggering non-alcoholic steatohepatitis (NASH) and HCC [683000]
  • Swiss Cancer League - [KLS-4505-08-2018]
  • Swiss National Science Foundation - Role of extracellular vesicles in chemotherapy-induced metastasis [188868]
  • EVIR Therapeutics -
  • Fondation pour la lutte contre le cancer -
  • Helmholtz Future topic Inflammation and Immunology -
  • Rainer-Hoenig foundation -
  • Swiss Institute for Experimental Cancer Research—ISREC Foundation -
  • Anita and Werner Damm-Etienne Foundation -
  • Association Frédéric Fellay -
Citation (ISO format)
GHASEMI, Ali et al. Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy. In: Nature cancer, 2023. doi: 10.1038/s43018-023-00668-y
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Article (Published version)
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Identifiers
ISSN of the journal2662-1347
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Technical informations

Creation12/12/2023 9:13:10 AM
First validation12/21/2023 1:39:05 PM
Update time02/21/2024 11:38:38 AM
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