Thansfection of oncogenes into dendritic cells utilizing receptor-mediated endocytosis of liposomes

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Liposomes represent a promising vehicle to deliver exogenous antigens to dendritic cells (DCs) for tumor immunotherapy. Targeting exogenous antigens to Fcγ receptors on DCs has been shown to result in efficient presentation of antigen-derived peptides on MHC class I as well as class II molecules. Here we investigated whether DCs that endocytosed physicochemically optimized, antigen-containing liposomes conjugated with IgG efficiently present antigens on MHC class I and class II molecules, and consequently induce strong anti-tumor immune responses. IgG-conjugated liposomes with 200 nm in diameter without attaching polyethylene glycol were most efficiently endocytosed by DCs. Human monocyte-derived DCs that endocytosed tetanus toxoid (TT)-containing IgG-liposomes via CD32 stimulated CD4^+ T cells more strongly than DCs pulsed with TT-containing bare liposomes or with soluble TT. Immunization of mice with DCs that endocytosed ovalbumin (OVA)-containing IgG-liposomes, but not OVA-containing bare liposomes or soluble OVA, completely prevented the growth of OVA-expressing lymphoma cells. Importantly, administration of DCs that endocytosed OVA-containing IgG-liposomes to the mice with established OVA-expressing tumors strongly suppressed tumor growth. This study demonstrates an IgG-liposome with physicochemical properties suitable for delivering antigens to DCs, and paves the way to the application of IgG-liposomes for tumor immunotherapy using DCs.