Induction of anti-tumor immune responses with oligomannose-coated liposomes targeting to peritoneal macrophages

We recently established a novel drug delivery system (DDS) using oligomannose-coated liposomes (OMLs) taken up by peritoneal phagocytic cells to carry anti-cancer drugs to milky spots known as a preferential metastatic site of gastric cancers (Ikehara et al. 2006. Cancer Res. 66: 8740-8748). In the present study, we applied this intraperitoneal DDS for systemic tumor immunotherapy employing ovalbumin (OVA) as a model antigen. The phagocytic cells ingesting the OMLs containing OVA (OML-OVA) injected into the peritoneal cavity were predominantly macrophages (Mϕ), as they showed adhesive characteristics and expressed F4/80 and CD11b almost exclusively. Peritoneal Mϕ taking up OML-OVA could activate OVA-specific CD8+ (from OT-I: OVA257-264/H-2Kb-specific) and CD4+ (from OT-II: OVA323-339/H-2Ab-specific) T cells much more effectively in vitro than those taking up soluble OVA. Furthermore, only the mice immunized with OML-OVA rejected E.G7-OVA (OVA-transfected EL4) but not EL4. These results indicate that the OMLs can also be used as an effective antigen delivery system for tumor immunotherapy activating both CD8+ and CD4+ T cell subsets.