Source:http://linkedlifedata.com/resource/pubmed/id/19561534
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2009-7-23
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| pubmed:abstractText |
Human leukocyte antigen (HLA)-A2.1 transgenic mice (HHD) represent a valuable model to study and predict the immunogenicity of vaccines against pathogens. However, HHD mice are unsuitable for in vivo studies of cancer vaccines against human tumor-associated antigens because they lack T-cell tolerance that is key to define the potency of the treatment. In this study, we developed HHD/carcinoembryonic antigen P(CEA) hybrid mice by breeding transgenic mice homozygous for CEA with HHD. These mice express human CEA, present epitopes solely through HLA-A2.1 molecules and constitute a unique in vivo animal model to study HLA-A2.1-restricted immune response of a human CEA-based vaccine. Owing to the immune tolerance, HHD/CEA mice show a limited immune response and expansion of a different and restricted T-cell receptor repertoire after antigen-specific stimulation. Our data show that genetic vectors expressing CEA and peptide-based vaccines are able to efficiently break immune tolerance against CEA and to elicit strong immune response against HLA-A2.1-restricted CEA epitopes. Most importantly, efficient lysis of human CEA+/HLA-A2.1+ tumor cells was observed and significant protection against HHD/CEA tumor cells was achieved in HHD/CEA-vaccinated mice. Hence, HHD/CEA provides a relevant model for the evaluation of the potential efficacy of human CEA-based vaccines.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinoembryonic Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/H-2 Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A2 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1537-4513
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
32
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
744-54
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| pubmed:meshHeading |
pubmed-meshheading:19561534-Adenoviridae,
pubmed-meshheading:19561534-Animals,
pubmed-meshheading:19561534-Cancer Vaccines,
pubmed-meshheading:19561534-Carcinoembryonic Antigen,
pubmed-meshheading:19561534-Cell Line, Tumor,
pubmed-meshheading:19561534-Cytotoxicity, Immunologic,
pubmed-meshheading:19561534-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:19561534-Epitopes,
pubmed-meshheading:19561534-Feces,
pubmed-meshheading:19561534-Female,
pubmed-meshheading:19561534-Flow Cytometry,
pubmed-meshheading:19561534-Gastrointestinal Tract,
pubmed-meshheading:19561534-H-2 Antigens,
pubmed-meshheading:19561534-HLA-A2 Antigen,
pubmed-meshheading:19561534-Humans,
pubmed-meshheading:19561534-Male,
pubmed-meshheading:19561534-Melanoma, Experimental,
pubmed-meshheading:19561534-Mice,
pubmed-meshheading:19561534-Mice, Inbred C57BL,
pubmed-meshheading:19561534-Mice, Transgenic,
pubmed-meshheading:19561534-Receptors, Antigen, T-Cell,
pubmed-meshheading:19561534-Transfection,
pubmed-meshheading:19561534-Vaccination
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| pubmed:year |
2009
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| pubmed:articleTitle |
A novel mouse model for evaluation and prediction of HLA-A2-restricted CEA cancer vaccine responses.
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| pubmed:affiliation |
Department of Oncology, I.R.B.M. P. Angeletti, Pomezia, Italy.
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| pubmed:publicationType |
Journal Article
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