Development of effective antigen delivery carrier to dendritic cells via Fc receptor in cancer immunotherapy

Abstract

In cancer immunotherapy with dendritic cells (DCs), which are the most potent antigen-presenting cells, it is important that DCs present peptides derived from tumor-associated antigens on major histocompatibility complex (MHC) class I molecules and activate tumor-specific cytotoxic T lymphocytes. However, exogenous antigens are generally presented on MHC class II but not class I molecules. To develop effective immunotherapy for cancer, an antigen delivery carrier that can induce MHC class I presentation of exogenous antigens is necessary. Several strategies to induce DCs to present exogenous antigens on MHC class I molecules have been reported. First, DCs that phagocytosed a particulate form of antigens present peptides derived from the antigens on MHC class I molecules. Second, DCs that incorporated antigens via certain endocytic receptors such as Fc receptors efficiently present peptides on MHC class I molecules. We combined these two strategies and prepared antigen-containing IgG-conjugated liposomes (IgG-liposomes). In this study, we investigated the feasibility of IgG-liposomes as antigen delivery carriers in cancer immunotherapy with DCs. 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. These results suggest that IgG-liposomes represent an efficient antigen delivery carrier for DCs in cancer immunotherapy. © 2007 The Pharmaceutical Society of Japan.