Source:http://linkedlifedata.com/resource/pubmed/id/11535168
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
13
|
| pubmed:dateCreated |
2001-9-5
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| pubmed:abstractText |
Hemophilia A patients are typically treated by factor VIII (FVIII) protein replacement, an expensive therapy that induces FVIII-specific inhibitors in approximately 30% of patients with severe hemophilia. FVIII gene therapy has the potential to improve the current treatment protocols. In this report, we used a hemophilia A mouse model to compare the humoral and cellular immune responses between an E1/E2a/E3-deficient adenovirus expressing human FVIII directed by a liver-specific albumin promoter and purified recombinant FVIII protein infusion. Adenovirus-mediated FVIII expression did not elicit detectable CD4+ or CD8+ T cell responses and induced a weak antibody immune response to FVIII. In contrast, FVIII protein administration resulted in a potent anti-FVIII antibody response and moderate CD4+ T cell response. Furthermore, hemophiliac mice preimmunized with FVIII protein infusion to induce anti-FVIII immunity, and subsequently treated by adenovirus-mediated FVIII gene therapy, expressed therapeutic levels of FVIII despite the presence of low levels of anti-FVIII antibodies. No FVIII was detected in the plasma of mice with intermediate or high antibody levels, although anti-FVIII antibody levels in some vector-treated animals declined. The data support the hypothesis that liver-specific gene therapy-mediated expression of FVIII may be less immunogenic than traditional protein replacement therapy.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Albumins,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Factor VIII,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Isotypes,
http://linkedlifedata.com/resource/pubmed/chemical/Ovalbumin
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
1043-0342
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
12
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1651-61
|
| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:11535168-Adenoviridae,
pubmed-meshheading:11535168-Albumins,
pubmed-meshheading:11535168-Animals,
pubmed-meshheading:11535168-Antibodies,
pubmed-meshheading:11535168-Disease Models, Animal,
pubmed-meshheading:11535168-Factor VIII,
pubmed-meshheading:11535168-Gene Expression,
pubmed-meshheading:11535168-Gene Therapy,
pubmed-meshheading:11535168-Genetic Vectors,
pubmed-meshheading:11535168-Hemophilia A,
pubmed-meshheading:11535168-Humans,
pubmed-meshheading:11535168-Immunoglobulin Isotypes,
pubmed-meshheading:11535168-Liver,
pubmed-meshheading:11535168-Mice,
pubmed-meshheading:11535168-Mice, Inbred C57BL,
pubmed-meshheading:11535168-Organ Specificity,
pubmed-meshheading:11535168-Ovalbumin,
pubmed-meshheading:11535168-Promoter Regions, Genetic,
pubmed-meshheading:11535168-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:11535168-Time Factors
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| pubmed:year |
2001
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| pubmed:articleTitle |
Adenovirus-mediated factor VIII gene expression results in attenuated anti-factor VIII-specific immunity in hemophilia A mice compared with factor VIII protein infusion.
|
| pubmed:affiliation |
DNA Viral Vectors Unit, Genetic Therapy, Inc., A Novartis Company, 9 West Watkins Mill Road, Gaithersburg, MD 20878, USA.
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| pubmed:publicationType |
Journal Article
|