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 cells 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 previously analyzed the capacity of DCs to interact with bacteria, and we have shown that bacteria can act as "Trojan horses," delivering heterologous proteins to DCs in a processed form that allows extremely efficient loading of both 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 induction of antitumor immunity has proven to be very ineffective. We have given mice injections of either Trp-2/recombinant bacteria-loaded DCs or with bacteria alone engineered to express the Trp-2 melanoma antigen. We have shown 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 well as in experiments of tumor therapy. When therapy with bacteria-loaded DCs was performed in B16 tumor-bearing mice, 60% of the treated mice were tumor free 2 months after the initial tumor growth.