Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2020-10-16 , DOI: 10.1073/pnas.2006186117 Alsya J. Affandi, Joanna Grabowska, Katarzyna Olesek, Miguel Lopez Venegas, Arnaud Barbaria, Ernesto Rodríguez, Patrick P. G. Mulder, Helen J. Pijffers, Martino Ambrosini, Hakan Kalay, Tom O’Toole, Eline S. Zwart, Geert Kazemier, Kamran Nazmi, Floris J. Bikker, Johannes Stöckl, Alfons J. M. van den Eertwegh, Tanja D. de Gruijl, Gert Storm, Yvette van Kooyk, Joke M. M. den Haan
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.