Novel oligomannose liposome-DNA complex DNA vaccination efficiently evokes anti-HPV E6 and E7 CTL responses.

Abstract

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.

• Authors: Masahito Mizuuchi, Yoshihiko Hirohashi, Toshihiko Torigoe, Takafumi Kuroda, Kazuyo Yasuda, Yoshitaka Shimizu, Tsuyoshi Saito, Noriyuki Sato
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 92 Issue 1 Pg. 185-90 (Feb 2012) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 22032938 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• DNA, Viral
• E6 protein, Human papillomavirus type 16
• HLA-A24 Antigen
• Liposomes
• Oligosaccharides
• Oncogene Proteins, Viral
• Papillomavirus E7 Proteins
• Repressor Proteins
• Vaccines, DNA
• oncogene protein E7, Human papillomavirus type 16
• Mannose

Topics

• Adult
• DNA, Viral (genetics)
• Female
• Genotype
• HLA-A24 Antigen (immunology)
• Humans
• Liposomes
• Lymphocyte Activation (immunology)
• Mannose (administration & dosage)
• Middle Aged
• Oligosaccharides (administration & dosage)
• Oncogene Proteins, Viral (immunology)
• Papillomaviridae (immunology)
• Papillomavirus E7 Proteins (immunology)
• Papillomavirus Infections (immunology, virology)
• Plasmids
• Repressor Proteins (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Uterine Cervical Neoplasms (immunology, virology)
• Vaccination
• Vaccines, DNA (administration & dosage)
• Uterine Cervical Dysplasia (immunology, virology)