Grabowska, JAffandi, A Jvan Dinther, DNijen Twilhaar, M KOlesek, KHoogterp, LAmbrosini, MHeijnen, D A MKlaase, LHidalgo, AndresAsano, KCrocker, PRStorm, Gvan Kooyk, Yden Haan, JMM2021-08-262021-08-262021-01J Control Release. 2021; 331:309-3201873-4995http://hdl.handle.net/20.500.12105/13314Cancer vaccines aim to efficiently prime cytotoxic CD8+ T cell responses which can be achieved by vaccine targeting to dendritic cells. CD169+ macrophages have been shown to transfer antigen to dendritic cells and could act as an alternative target for cancer vaccines. Here, we evaluated liposomes containing the CD169/Siglec-1 binding ligand, ganglioside GM3, and the non-binding ligand, ganglioside GM1, for their capacity to target antigens to CD169+ macrophages and to induce immune responses. CD169+ macrophages demonstrated specific uptake of GM3 liposomes in vitro and in vivo that was dependent on a functional CD169 receptor. Robust antigen-specific CD8+ and CD4+ T and B cell responses were observed upon intravenous administration of GM3 liposomes containing the model antigen ovalbumin in the presence of adjuvant. Immunization of B16-OVA tumor bearing mice with all liposomes resulted in delayed tumor growth and improved survival. The absence of CD169+ macrophages, functional CD169 molecules, and cross-presenting Batf3-dependent dendritic cells (cDC1s) significantly impaired CD8+ T cell responses, while B cell responses were less affected. In conclusion, we demonstrate that inclusion of GM3 in liposomes enhance immune responses and that splenic CD169+ macrophages and cDC1s are required for induction of CD8+ T cell immunity after liposomal vaccination.engVoRhttp://creativecommons.org/licenses/by/4.0/LiposomesT-LymphocytesAnimalsCD8-Positive T-LymphocytesDendritic CellsMacrophagesMiceMice, Inbred C57BLOvalbuminAtribución 4.0 Internacional33493613331309-32010.1016/j.jconrel.2021.01.029Journal of controlled release : official journal of the Controlled Release Societyopen access