An autologous oral DNA vaccine protects against murine melanoma

We demonstrated that peripheral T cell tolerance toward murine melanoma sel f-antigens gp100 and TRP-2 can be broken by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to minigenes encoding peptide ep itopes gp100(25-33) and TRP-2(181-188). These epitopes contain dominant anc hor residues for MHC class I antigen alleles H-2D(b) and H-2K(b), respectiv ely. The DNA vaccine was delivered by oral gavage by using an attenuated st rain of Salmonella typhimurium as carrier. Tumor-protective immunity was me diated by MHC class I antigen-restricted CD8(+) T cells that secreted T(H)1 cytokine IFN-gamma and induced tumor rejection and growth suppression afte r a lethal challenge with B16G3.26 murine melanoma cells. Importantly, the protective immunity induced by this autologous DNA Vaccine against murine m elanoma cells was at least equal to that achieved through xenoimmunization with the human gp100(25-33) peptide, which differs in its three NH2-termina l amino acid residues from its murine counterpart and was previously report ed to be clearly superior to an autologous vaccine in inducing protective i mmunity. The presence of ubiquitin upstream of the minigene proved to be es sential for achieving this tumor-protective immunity, suggesting that effec tive antigen processing and presentation may make it possible to break peri pheral T cell tolerance to a self-antigen. This vaccine design might prove useful for future rational designs of other recombinant DNA vaccines target ing tissue differentiation antigens expressed by tumors.