Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.
Details
Serval ID
serval:BIB_4DE2DD03AF35
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.
Journal
Nature cancer
ISSN
2662-1347 (Electronic)
ISSN-L
2662-1347
Publication state
Published
Issued date
02/2024
Peer-reviewed
Oui
Volume
5
Number
2
Pages
240-261
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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 <sup>+</sup> 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.
Keywords
Humans, Mice, Animals, Cytokines, Immunotherapy, Dendritic Cells, Neoplasms/therapy, Interleukin-12
Pubmed
Web of science
Open Access
Yes
Create date
01/12/2023 10:39
Last modification date
08/08/2024 7:33