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- W2967393497 abstract "1286 Objective: Previously we have designed DNA vaccines against HPV-16 E7 using intracellular targeting strategies that enhance MHC class I presentation. These vaccines have demonstrated significantly enhanced potency, generating strong E7-specific CD8+ antitumor immunity. In this study, we attempted to characterize the cytotoxic T lymphocyte (CTL) responses induced by a DNA vaccine encoding calreticulin (CRT) linked to HPV-16 E7 in HLA-A2/AAD transgenic mice. Material and Methods: The HLA-A2/AAD gene was transduced into a HPV-16 E6 and E7-expressing tumor cell line, TC-1, to generate TC-1/AAD. HLA-A2/AAD transgenic mice on C57BL/6 background were immunized with pcDNA3-CRT/E7, pcDNA3-CRT/mtE7 (E7 with aa49-57 deletion), or control DNA via gene gun. Splenocytes from immunized mice were stimulated with E7 peptides to identify E7-specific immune responses using IFN-r intracellular staining. Antitumor effect was tested by TC-1/AAD. Results: The H-2Db-restricted E7 aa49-57 epitope suppressed the presentation of HLA-A2-restricted epitopes, since the CD8+ T cell immune response induced by CRT/E7 in HLA-A2/AAD transgenic mice is E7 aa49-57 dominant. However, only an HLA-A2-restricted E7 aa11-20 dominant immune response was observed when E7 aa49-57 was removed. This HLA-A2-restricted E7 aa11-20 specific immune response prevented TC-1/AAD growth in the HLA-A2/AAD transgenic mice. Conclusions: In this study, an HPV-16 E6 and E7 expressing HLA-A2 mouse tumor model was established to test HPV-16 E7 DNA vaccines. In HLA-A2/AAD transgenic mice, H-2Db-restricted E7 aa49-57 epitope suppressed the presentation of E7 HLA-A2 epitopes. Removal of this H-2Db-restricted epitope generated an HLA-A2-restricted E7 aa11-20 dominant immune response. This immune response was able to prevent E7-expressing HLA-A2 tumor growth. Relevance of this study to the design of HPV-16 E7 vaccine was discussed." @default.
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- W2967393497 date "2004-04-01" @default.
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- W2967393497 title "Characterization of HPV-16 E7-specific cytotoxic T lymphocyte responses in HLA-A*0201 transgenic mice induced by DNA vaccines" @default.
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