Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.
Nat Cancer
; 5(2): 240-261, 2024 Feb.
Article
em 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.
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citocinas
/
Neoplasias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Cancer
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suíça