An HLA-A2 polyepitope vaccine for melanoma immunotherapy

Epitope-based vaccination strategies designed to induce tumor-specific CDS CTL, are being widely considered for cancer immunotherapy, Here we describe a recombinant poxvirus vaccine that codes for ten HLA-A2-restricted epitop es derived from five melanoma Ags conjoined in an artificial polyepitope or polytope construct. Target cells infected with the melanoma polytope vacci nia were recognized by three different epitope-specific CTL lines derived f rom HLA-A2 melanoma patients, and CTL responses to seven of the epitopes we re generated in at least one of six HLA-A2-transgenic mice immunized with t he construct. CTL lines derived from vaccinated transgenic mice were also a ble to kill melanoma cells in vitro. Multiple epitopes within the polytope construct were therefore shown to be individually immunogenic, illustrating the feasibility of the polytope approach for melanoma immunotherapy. Tumor escape from CTL surveillance, through down regulation of individual tumor Ags and MHC alleles, might be overcome by polytope vaccines, which simultan eously target multiple cancer Ags.