Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes.
Alsya A AffandiJoanna GrabowskaKatarzyna OlesekMiguel Lopez VenegasArnaud BarbariaErnesto RodríguezPatrick P G MulderHelen J PijffersMartino AmbrosiniHakan KalayTom O'TooleEline S ZwartGeert KazemierKamran NazmiFloris J BikkerJohannes StöcklAlfons J M van den EertweghTanja D de GruijlGert StormYvette van KooykJoke M M den HaanPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
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.