849 Optimization of a GM3-containing liposomal vaccine that delivers antigen to CD169+ splenic macrophages

Background Although promising developments in cancer vaccination have been made, therapeutic effectiveness is often insufficient. Liposomal vaccine effectiveness could be enhanced by antigen encapsulation and incorporation of molecules that actively target to antigen presenting cells to enhance T cell activation. CD169-expressing splenic macrophages are located in the marginal zone and efficiently capture particulate antigens such as viruses and exosomes from the blood circulation. Upon antigen capture CD169+ macrophages transfer antigen to cross-presenting dendritic cells that are responsible for the activation of CD8+ T cells. Methods Here we prepared liposomes that contain a physiological ligand for CD169, the ganglioside GM3, to facilitate uptake by CD169+ macrophages. We assessed how various amounts of targeting molecule GM3, decoration with PEG and liposomal size affected binding and uptake by CD169+ macrophages in vitro and in vivo. In addition, we evaluated the stability of liposomal preparations in plasma. As a proof of concept, we prepared GM3-liposomes with a long ovalbumin peptide and tested the capacity of these liposomes to induce CD8+ and CD4+ T cell activation and compared it to control liposomes and soluble peptide. Results These data indicate that targeting of splenic CD169 macrophages can be optimized by careful selection of constituents of the liposomal delivery vehicle. Moreover, optimized GM3-mediated liposomal targeting to CD169 macrophages results in potent immune responses. Conclusions GM3-mediated liposomal targeting to CD169 macrophages presents as a promising strategy for cancer vaccines Ethics Approval All animal experiments were approved by the local animal welfare body.