Gene gun-mediated DNA vaccination induces antitumor immunity against humanpapillomavirus type 16 E7-expressing murine tumor metastases in the liver and lungs

DNA vaccination has emerged as an attractive approach for tumor immunothera py. The aim of this study was to evaluate the potency of DNA vaccines in pr eventing and treating the liver and lung metastases of a human papillomavir us-16 (HPV-16) E7-expressing murine tumor (TC-1). We used the gene gun meth od to vaccinate C57BL/6 mice intradermally with DNA vaccines containing the HPV-16 E7 gene, the E7 ene linked to the sorting signals of the lysosome-a ssociated membrane protein-1 (Sig/E7/LAMP-1). or the 'empty' plasmid vector . The in vivo antitumor immunity was analyzed in both tumor prevention and tumor regression experiments. In addition, cytotoxic T lymphocyte (CTL) ass ays, enzyme-linked immunospot assay and enzyme-linked immunoabsorbent assay were used to assess the E7-specific T cell-mediated and humoral immunity. Mice vaccinated with Sig/E7/LAMP-1 DNA generated the strongest E7-specific CTL activities, the highest numbers of E7-specific CD8(+) cell precursors a nd the highest titers of E7-specific antibodies. While both E7 DNA and Sig/ E7/LAMP-1 DNA generated potent antitumor immunity in the liver and lung met astases models, the Sig/E7/LAMP-1 DNA was more potent under stringent condi tions. DNA vaccination with E7-expressing plasmids was effective in control ling liver and lung metastases of an E7-expressing murine tumor. Our data s uggest that antigen-specific DNA vaccination can potentially he applied to control liver and lung metastases of tumors with defined tumor-specific ant igens.