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rdf:type |
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lifeskim:mentions |
umls-concept:C0008109,
umls-concept:C0019733,
umls-concept:C0026809,
umls-concept:C0039195,
umls-concept:C0205195,
umls-concept:C0280527,
umls-concept:C0302350,
umls-concept:C0355642,
umls-concept:C0376659,
umls-concept:C0445202,
umls-concept:C0677582,
umls-concept:C0871261,
umls-concept:C1325725,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1999177,
umls-concept:C2911692
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pubmed:issue |
12
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pubmed:dateCreated |
2006-4-3
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pubmed:abstractText |
We identified the strategies to induce a CTL response to human papillomavirus (HPV) 16 E2 in HLA-A2 transgenic mice (AAD). A chimeric HPV16 virus-like particle (VLP) that includes full length HPV16 E7 and E2 (VLP-E7E2) was generated. The combination of E2 and E7 has the advantage that E2 is expressed in early dysplasia and neoplasia lesions, where E7 is expressed in more advance lesions. Since T cell response to E2 is less defined, we first evaluated the strategies to enhancing CD8(+) T cell responses to HPV E7, using different combinations of immune-modulators with VLP-E7E2. Data showed that the CTL response to E7 could be significantly enhanced by coinjection of GM-CSF and anti-CD40 antibodies with chimeric VLP-E7E2 without adjuvant. However, using the same combination, a low level of CD8(+) T cell response to E2 was detected. To enhance the CD8+ T cell response to E2, we analyzed T cell epitopes from E2 sequence. A heterogenous prime-boost with chimeric VLP-E7E2 and E2 peptides was performed. The data showed that the priming with chimeric VLP-E7E2, followed by boosting with E2 peptides, gave a better CTL response than 2 immunizations with E2 peptides. The enhanced immunity is due to the increase of CD11c(+) and CD11c(+) CD40(+) double positive dendritic cells in mice that received immune-modulators, GM-CSF and anti-CD40. Furthermore, the level of anti-L1 antibodies remains similar in mice immunized with chimeric VLP with/without immune-modulators. Thus, the data suggested that the chimeric VLP-E7E2 has a therapeutic potential for the treatment of HPV-associated CINs and cancer without diminishing VLPs potential as a prophylactic vaccine by inducing anti-L1 antibodies against free virus.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD11c,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD40,
http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E2 protein, Human papillomavirus...,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A2 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Leukocyte L1 Antigen Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Papillomavirus E7 Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/oncogene protein E7, Human...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0020-7136
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2006 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
118
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3022-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16425257-Animals,
pubmed-meshheading:16425257-Antibodies, Viral,
pubmed-meshheading:16425257-Antigens, CD11c,
pubmed-meshheading:16425257-Antigens, CD40,
pubmed-meshheading:16425257-CD8-Positive T-Lymphocytes,
pubmed-meshheading:16425257-Cancer Vaccines,
pubmed-meshheading:16425257-DNA-Binding Proteins,
pubmed-meshheading:16425257-Dendritic Cells,
pubmed-meshheading:16425257-Drug Therapy, Combination,
pubmed-meshheading:16425257-Epitopes, T-Lymphocyte,
pubmed-meshheading:16425257-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:16425257-HLA-A2 Antigen,
pubmed-meshheading:16425257-Humans,
pubmed-meshheading:16425257-Leukocyte L1 Antigen Complex,
pubmed-meshheading:16425257-Mice,
pubmed-meshheading:16425257-Mice, Transgenic,
pubmed-meshheading:16425257-Oncogene Proteins, Fusion,
pubmed-meshheading:16425257-Oncogene Proteins, Viral,
pubmed-meshheading:16425257-Papillomavirus E7 Proteins,
pubmed-meshheading:16425257-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:16425257-Viral Fusion Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
Combined prophylactic and therapeutic cancer vaccine: enhancing CTL responses to HPV16 E2 using a chimeric VLP in HLA-A2 mice.
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pubmed:affiliation |
Vaccine Branch, NCI, National Naval Medical Center, Bldg 8, Bethesda, MD 20892, USA. qinanj@mailnih.gov
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pubmed:publicationType |
Journal Article
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