Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.
Nat Cancer
; 5(2): 240-261, 2024 Feb.
Article
in En
| MEDLINE
| ID: mdl-37996514
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytokines
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Cancer
Year:
2024
Document type:
Article
Affiliation country: