| Novel oligomannose liposome-DNA complex DNA vaccination efficiently evokes anti-HPV E6 and E7 CTL responses. | |
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MedLine Citation:
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PMID: 22032938 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The aim of this study was to establish an efficient human papilloma virus (HPV) type 16-targeting cancer immunotherapy. Persistent high-risk HPV infection causes cervical intra-epithelial neoplasia (CIN) and subsequent cervical carcinoma. HPV type16 (HPV16) is one of the common carcinogenic types and is found in about 50% of invasive cervical carcinomas. HPV16-derived viral proteins E6 and E7 are expressed in cancerous cells through the progression of the disease and have a role in carcinogenesis but are not expressed in normal cells. Thus, these proteins are regarded as ideal antigens for cervical carcinoma immunotherapy. In this study, we generated a novel HPV 16 E6 and E7 gene plasmid containing oligomannose liposomes (OML-HPV). We compared the cytotoxic T lymphocyte (CTL) induction efficiency of OML-HPV and that of standard liposome-HPV16 E6 and E7 DNA complex. HPV16 E6-specific CTLs could be generated from HPV 16-positive cervical carcinoma patient's peripheral blood mononuclear cells (PBMCs) by stimulating OML-HPV, but could not by stimulating standard liposome-HPV 16 E6, E7 DNA complex. Furthermore, we screened HLA-A24-restricted HPV16 E6- and E7-derived peptides, and found that one E6-derived peptide (E6 66-74) showed the highest immunogenicity with ELISPOT assay from 100% of HPV16-positive patients (4 out of 4). On the other hand, other E6- or E7-derived peptides, including E6 49-57, E6 82-90, E6 87-95, E6 98-106 and E7 83-93, showed less frequent reactivity. These results indicate that OML-HPV is a more effective approach than DNA vaccination using standard liposomes, and that a novel HLA-A24-restricted peptide, E6 66-74, might be a suitable target of cervical cancer immunotherapy. |
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Authors:
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Masahito Mizuuchi; Yoshihiko Hirohashi; Toshihiko Torigoe; Kuroda Takafumi; Kazuyo Yasuda; Tsuyoshi Saito; Noriyuki Sato |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-15 |
Journal Detail:
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Title: Experimental and molecular pathology Volume: - ISSN: 1096-0945 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370711 Medline TA: Exp Mol Pathol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Inc. |
Affiliation:
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Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo 060-8556, Japan; Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo 060-8556, Japan. |
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