Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 44, Pages 27528-27539Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2006186117
Keywords
Siglec-1; CD169; dendritic cells; CD8(+) T cells; vaccination
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Funding
- Dutch Cancer Society [VU2016-10449]
- Phospholipid Research Center
- NWO ZonMW [TOP 91218024]
- EU Research Framework Program [H2020-MSCA-ITN-2014-ETN-642870]
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Priming of CD8(+) T cells by dendritic cells (DCs) is crucial for the generation of effective antitumor immune responses. Here, we describe a liposomal vaccine carrier that delivers tumor antigens to human CD169/Siglec-1(+) antigen-presenting cells using gangliosides as targeting ligands. Ganglioside-liposomes specifically bound to CD169 and were internalized by in vitro-generated monocyte-derived DCs (moDCs) and macrophages and by ex vivo-isolated splenic macrophages in a CD169-dependent manner. In blood, high-dimensional reduction analysis revealed that ganglioside-liposomes specifically targeted CD14(+) CD169(+) monocytes and Axl(+) CD169(+) DCs. Liposomal codelivery of tumor antigen and Toll-like receptor ligand to CD169(+) moDCs and Axl(+) CD169(+) DCs led to cytokine production and robust cross-presentation and activation of tumor antigen-specific CD8(+) T cells. Finally, Axl(+) CD169(+) DCs were present in cancer patients and efficiently captured ganglioside-liposomes. Our findings demonstrate a nanovaccine platform targeting CD169(+) DCs to drive antitumor T cell responses.
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