Dendritic cells, loaded with recombinant bacteria expressing tumor antigens, induce a protective tumor-specific response

Dendritic cells (DCs) are considered the most potent antigen-presenting cel ls and probably the only ones able to prime naive T cells, Indeed, DCs are distributed in tissues that interface the external environment, where they act as sentinels for incoming bacteria, viruses, and fungi, We have previou sly analyzed the capacity of DCs to interact with bacteria, and we have sho wn that bacteria can act as "Trojan horses," delivering heterologous protei ns to DCs in a processed form that allows extremely efficient loading of bo th MHC class I and class II molecules, In this study, we have optimized the usage of recombinant bacteria as an antigen delivery system for DCs, with the aim to develop a new DC vaccination strategy in antitumor immunity. We have focused on a low immunogenic antigen, the tyrosinase-related protein-2 (Trp-2), a self-antigen expressed in mouse and human melanoma for which in duction of antitumor immunity has proven to be very ineffective. We have gi ven mice injections of either Trp-2/recombinant bacteria-loaded DCs or with bacteria alone engineered to express the Trp-2 melanoma antigen. We have s hown that only DCs loaded with recombinant bacteria, but not with wild-type bacteria, were able to induce Trp-2-specific CTLs and immunity against the B16 tumor, Immunity was obtained in experiments of tumor vaccination as we ll as in experiments of tumor therapy. When therapy with bacteria-loaded DC s was performed in B16 tumor-bearing mice, 60% of the treated mice were tum or free 2 months after the initial tumor growth.