Dendritic cell (DC)-hased vaccines have shown encouraging results in treating cancers in animal models and clinical trials.However, most DC-based vaccines require tedious and costly manipulations of DC ex vivo.More potent cancer vaccines capable of targeting immature DC in vivo and bypassing the ex vivo manipulations, are critically needed.In the past 5 years, we have been taking a "reverse immunology" approach in order to understand why a scarcely expressed prostate cancer antigen NY-ESO-1 induces spontaneous T cell and antibody responses.Distinctively strong immune responses even occur in patients with late-stage cancers, which are associated with a dominant immune-suppressive tumor environment.In search of intrinsic factors or molecular patterns contributing to the immunogenicity of NY-ESO-1, we find that the NY-ESO-1 protein binds to complement Clq receptor on the surface of innate immune cells including dendritic cells and macrophages.Consequently, NY-ESO-1 induces phagocytosis coupled with DC maturation in vitro.These intrinsic properties dictate NY-ESO-1 to serve as its own adjuvant, which may provide explanation why intracellularly expressed NY-ESO-1 induces an impressive immune response.We have constructed NY-ESO-1 fusion vaccines and are now investigating the immunological and anti-tumor properties of DC-targeting vaccines in vivo in B 16 melanoma and Myc-CaP prostate cancer models.