Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1999-12-14
pubmed:abstractText
DNA vaccination is an attractive approach for tumor immunotherapy because of its stability and simplicity of delivery. Advances demonstrate that helper T cell responses play a critical role in initiating immune responses. The aim of the current study is to test whether targeting HPV-16 E7 to the endosomal/lysosomal compartment can enhance the potency of DNA vaccines. We linked the lysosome-associated membrane protein 1 (LAMP-1) to HPV-E7 to construct a chimeric DNA, Sig/E7/LAMP-1 DNA. For in vivo tumor prevention experiments, mice were vaccinated with E7 DNA or Sig/E7/LAMP-1 DNA via gene gun, followed by tumor challenge. For in vivo tumor regression experiments, mice were first challenged with tumor cells and then vaccinated with E7-DNA or Sig/E7/LAMP-1 DNA. Intracellular cytokine staining with flow cytometry analysis, cytotoxic T lymphocyte (CTL) assays, enzyme-linked immunoabsorbent assay (ELISA), and enzyme-linked immunospot (ELISPOT) assays were used for in vitro E7-specific immunological studies. In both tumor prevention and tumor regression assays, Sig/E7/LAMP-1 DNA generated greater antitumor immunity than did wild-type E7 DNA. In addition, mice vaccinated with Sig/E7/LAMP-1 DNA had greater numbers of E7-specific CD4+ helper T cells, higher E7-specific CTL activity, and greater numbers of CD8+ T cell precursors than did mice vaccinated with Sig/E7 or wild-type E7 DNA. Sig/E7 generated a stronger E7-specific antibody response than did Sig/E7/LAMP-1 or wild-type E7 DNA. Our results indicate that linkage of the antigen gene to an endosomal/lysosomal targeting signal may greatly enhance the potency of DNA vaccines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2727-40
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:10584920-Animals, pubmed-meshheading:10584920-Antigens, CD, pubmed-meshheading:10584920-CD4-Positive T-Lymphocytes, pubmed-meshheading:10584920-CD8-Positive T-Lymphocytes, pubmed-meshheading:10584920-Dendritic Cells, pubmed-meshheading:10584920-Endosomes, pubmed-meshheading:10584920-Histocompatibility Antigens Class I, pubmed-meshheading:10584920-Lysosome-Associated Membrane Glycoproteins, pubmed-meshheading:10584920-Lysosomes, pubmed-meshheading:10584920-Membrane Glycoproteins, pubmed-meshheading:10584920-Mice, pubmed-meshheading:10584920-Mice, Inbred C57BL, pubmed-meshheading:10584920-Neoplasms, Experimental, pubmed-meshheading:10584920-Oncogene Proteins, Viral, pubmed-meshheading:10584920-Papillomavirus E7 Proteins, pubmed-meshheading:10584920-Protein Sorting Signals, pubmed-meshheading:10584920-Vaccines, DNA
pubmed:year
1999
pubmed:articleTitle
Targeting human papillomavirus type 16 E7 to the endosomal/lysosomal compartment enhances the antitumor immunity of DNA vaccines against murine human papillomavirus type 16 E7-expressing tumors.
pubmed:affiliation
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't