Linked Life Data

10584928

Source:http://linkedlifedata.com/resource/pubmed/id/10584928

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1999-12-14
pubmed:abstractText
In animals, Ad-mediated gene transfer initiates anti-Ad host immune responses that vary, depending on vector design, dose, host, and transgene. To begin to understand whether the anti-Ad vector responses in humans simulate those in animals, Ad(GV)CD.10, an E1-E3- Ad5 vector encoding the E. coli cytosine deaminase gene, was administered by the intradermal route to six normal individuals (8 x 10(7) to 8 x 10(9) particle units, each dose administered to two sites; n = 2 per group). No adverse events were observed. Polymerase chain reaction/Southern analysis demonstrated vector genome in the skin through 28 days in all individuals except one of two at the lowest dose. Local induration, independent of vector dose and baseline systemic anti-Ad5 neutralizing antibodies, developed in all subjects (6 to 17 mm, peak by day 3). Biopsies revealed a mild to moderate T cell (CD3+, CD4+, CD8+), B cell, and macrophage infiltrate at day 3, all decreased by day 28. Langerhans cells accumulated primarily in the papillary dermis. The day 3 cellular response was dose independent. On day 28, CD4+ and CD8+ T lymphocytes and macrophages showed dose dependency. There was minimal systemic Ad5-specific lymphocyte proliferation induced by Ad vector administration in three individuals studied, and no Ad5-specific cytotoxic T lymphocytes (evaluated in two subjects) could be detected. Thus, intradermal administration of an E1-E3- Ad vector to normal subjects induces mild/moderate local cellular responses, even in Ad-immunized individuals. These observations provide a baseline to determine if these human anti-Ad vector host responses can be circumvented by using "stealth" vectors and/or immunosuppression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
2823-37
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Cellular immune responses of healthy individuals to intradermal administration of an E1-E3- adenovirus gene transfer vector.
pubmed:affiliation
Department of Medicine, Weill Medical College of Cornell University-New York Presbyterian Hospital, NY 10021, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't