Abstract
Induction of cancer-specific cellular immunity is necessary for establishment of cancer immunotherapy. For induction of cellular immunity, antigen delivery to immunocompetent cells such as dendritic cells and activation of these cells into a suitable state for immunity-induction are required. Here, intracellular antigen delivery systems have been developed using antigen-loaded liposomes modified with pH-responsive fusogenic polymers. Furthermore, polysaccharide-based pH-responsive polymers have been synthesized by introduction of carboxylated moieties to utilize polysaccharide-derived immunity-activation functions. Polysaccharide derivative-modified liposomes were taken up by dendritic cells efficiently and achieved cytoplasmic delivery of antigenic proteins via membrane fusion with endosomal membranes responding to weakly acidic pH in endosomes. After subcutaneous administration of these liposomes to mice, antigen-specific cellular immunity was induced by cytoplasmic delivery of antigen and activation property of immune cells derived from the polysaccharide backbone. In addition, combination of polysaccharide derivative-modified liposomes and TGF-β signaling inhibitor-embedded PEG-modified liposomes induced strong antitumor effects in tumor-bearing mice through induction of cellular immunity and cancelling of immunosuppression by the tumor.
