Cancer immunotherapy has gained much attention because of the recent success of
immune checkpoint inhibitors. Nevertheless, clinical
therapeutic effects of
immune checkpoint inhibitors remain limited, probably because most patients have other
immune checkpoint molecules or because they lack
cancer-specific cytotoxic T lymphocytes. Induction of
cancer-specific cytotoxic T lymphocytes requires efficient
antigen delivery systems that can convey
cancer antigens specifically to antigen presenting cells, promote the endosomal escape of
antigen into cytosol, and activate immune cells. Earlier, we reported cytoplasmic delivery systems of
antigen using pH-sensitive
polymer-modified
liposomes. Adjuvant molecules were further incorporated into these
liposomes to provide activation properties of cellular immune responses. This study further introduced cell specificity to these liposomal systems using
hyaluronic acid-based pH-sensitive
polymers, which are recognized by CD44 expressing on antigen presenting cells. pH-Sensitive
hyaluronic acid derivative-modified
liposomes showed much higher cellular association to antigen presenting cells than to fibroblasts with less CD44 expression. These
liposomes achieved the delivery of model antigenic
proteins into cytosol of dendritic cells and promoted Th1
cytokine production from the cells. Subcutaneous administration of these
liposomes to mice induced
antigen-specific cellular immune response in the spleen, leading to
tumor regression in
tumor-bearing mice. The results show that pH-sensitive
hyaluronic acid derivative-modified
liposomes are promising as multifunctional
antigen carriers having cell-specificity, cytoplasmic
antigen delivery performance, and adjuvant property to induce
antigen-specific cellular immunity.