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Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 11/3/2020, Vol. 117 Issue 44, p1-12. 12p. - Publication Year :
- 2020
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TUMOR antigens
*CANCER vaccines
*ANTIGEN receptors
*T cells
*DENDRITIC cells
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 117
- Issue :
- 44
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 146843754
- Full Text :
- https://doi.org/10.1073/pnas.2006186117