Induction Of Tumor-associated Antigen-specific Protective And Therapeutic Antitumor Immunity Using A Novel Chemo-antigen DNA Vaccine

DNA vaccination has become an attractive immunization strategy against tumor. It has been shown to elicit both strong and persistent antibody and CTL responses against antigens synthesized in vivo after direct introduction of the DNA encoding sequences and therefore is potent to induce antitumor effects. In this study, we evaluated the antitumor effects of gene gun-mediated a Chemo-antigen DNA Vaccine (pcDNA3.1-SLC-HP-Fc) in C57BL/6 mice.Recombinant DNA technologies have opened the possibility to develop multiepitope vaccines in a relatively rapid and efficient way. We developed a novel strategy for the APCs to efficiently cross-present a fusion tumor antigen, which contains c-erbB-2, p53 containing CTL epitopes, to both MHC class I and class II in a cognate manner. Specially, the NH₂ terminus of the fusion c-erbB-2, p53 (HP)gene was linked to a leader sequence ( human secondary lymphoid-tissue chemokine, SLC ) for secretion and chemokinesis, and the COOH terminus of the fusion gene was linked to a cell-binding domain (Fc portion of IgG₁) for receptor-mediated internalization. An eukaryotic expression vector, pcDNA3.1, was used for this study.On the other hand, we generated B16F10-sig-HP melanoma cells as target cells that express human c-erbB-2 and p53 fusion gene by transfecting the cultured cell line B16F10 with pcDNA-s-HP, which is constructed by cloning the truncated extracellular part of human c-erbB-2...