期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：44
页码：27528-27539
DOI：10.1073/pnas.2006186117
出版社：The National Academy of Sciences of the United States of America
摘要：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.
