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

Authors
Chen, CH; Ji, H; Suh, KW; Choti, MA; Pardoll, DM; Wu, TC
Citation
Gene therapy, 6(12):1972-1981, 1999
Journal Title
Gene therapy
ISSN
0969-71281476-5462
Abstract
DNA vaccination has emerged as an attractive approach for tumor immunotherapy. The aim of this study was to evaluate the potency of DNA vaccines in preventing and treating the liver and lung metastases of a human papillomavirus-16 (HPV-16) E7-expressing murine tumor (TC-1). We used the gene gun method to vaccinate C57BL/6 mice intradermally with DNA vaccines containing the HPV-16 E7 gene, the E7 gene linked to the sorting signals of the lysosome-associated 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) assays, 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 and 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 metastases models, the Sig/E7/LAMP-1 DNA was more potent under stringent conditions. DNA vaccination with E7-expressing plasmids was effective in controlling liver and lung metastases of an E7-expressing murine tumor. Our data suggest that antigen-specific DNA vaccination can potentially be applied to control liver and lung metastases of tumors with defined tumor-specific antigens.
MeSH terms
AnimalsAntibodies, Neoplasm/analysisAntigens, CD/geneticsBiolistics/methodsGenetic Vectors/administration & dosageLiver Neoplasms/immunologyLiver Neoplasms/secondary*Liver Neoplasms/therapyLung Neoplasms/immunologyLung Neoplasms/secondary*Lung Neoplasms/therapyLysosome-Associated Membrane GlycoproteinsMaleMembrane Glycoproteins/geneticsMiceMice, Inbred StrainsNeoplasms, Experimental/immunologyNeoplasms, Experimental/therapyOncogene Proteins, Viral/genetics*Oncogene Proteins, Viral/metabolismPapillomaviridae/immunology*Papillomavirus E7 ProteinsPapillomavirus Infections/immunologyPapillomavirus Infections/therapyT-Lymphocytes, Cytotoxic/immunologyTumor Virus Infections/immunologyTumor Virus Infections/therapy*Vaccines, DNA/administration & dosage*Vaccines, DNA/therapeutic use
DOI
10.1038/sj.gt.3301067
PMID
10637448
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
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