Document Detail


Both antigen optimization and lysosomal targeting are required for enhanced anti-tumour protective immunity in a human papillomavirus E7-expressing animal tumour model.
MedLine Citation:
PMID:  16162274     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
DNA immunization is a new approach for cancer immune therapy. In this study, we constructed human papillomavirus (HPV) 16 E7 expression vector cassettes and then compared the abilities of these constructs to induce antitumour protection. Lysosome-targeted E7 antigens, and to a lesser degree signal sequence-conjugated and transmembrane region sequence-conjugated E7 antigens in a DNA form, displayed tumour protection significantly higher than wild-type E7 antigens. This enhanced tumour protection was mediated by CD8+ cytotoxic T lymphocytes (CTL), as determined by in vivo T-cell depletion and in vitro interferon-gamma (IFN-gamma) production. Subsequent co-injection with interleukin-12-expressing cDNA showed insignificantly enhanced antitumour protection. However, E7 codon optimization plus lysosomal targeting resulted in a dramatic enhancement in antitumour protection both prophylactically and therapeutically through augmentation of the E7-specific CTL population, compared to either one of them alone. However, wild-type or codonoptimized E7 antigens without intracellular targeting displayed no protection against tumour challenge. Thus, these data suggest that antigen codon optimization plus lysosomal targeting strategy could be important in crafting more efficacious E7 DNA vaccines for tumour protection.
Authors:
Mi Suk Kim; Jeong-Im Sin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  116     ISSN:  0019-2805     ISO Abbreviation:  Immunology     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-09-15     Completed Date:  2005-11-10     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  255-66     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynaecology, School of Medicine, Catholic Universit of Daegu, Namgu, Daegu, Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Viral / biosynthesis
CD8-Positive T-Lymphocytes / immunology
Cancer Vaccines / immunology*
Codon / genetics
Disease Models, Animal
Female
Immunity, Cellular
Interferon-gamma / biosynthesis
Interleukin-12 / biosynthesis
Lysosomes
Mice
Mice, Inbred C57BL
Neoplasm Transplantation
Oncogene Proteins, Viral / genetics,  immunology,  metabolism*
Papillomaviridae / immunology
Papillomavirus E7 Proteins
Tumor Cells, Cultured
Uterine Cervical Neoplasms / immunology,  prevention & control*,  therapy
Vaccines, DNA / immunology*
Chemical
Reg. No./Substance:
0/Antibodies, Viral; 0/Cancer Vaccines; 0/Codon; 0/Oncogene Proteins, Viral; 0/Papillomavirus E7 Proteins; 0/Vaccines, DNA; 0/oncogene protein E7, Human papillomavirus type 16; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma
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