Linked Life Data

7640345

Source:http://linkedlifedata.com/resource/pubmed/id/7640345

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-9-19
pubmed:abstractText
Results of clinical trials have indicated that cA2, a neutralizing mouse/human IgG1 chimeric anti-human TNF-alpha monoclonal antibody, may have therapeutic benefit for rheumatoid arthritis patients. Arthritic joints contain, in addition to elevated levels of soluble TNF-alpha, high numbers of CD4+ T cells and macrophages, cells known to express transmembrane TNF-alpha upon activation. For that reason, we sought to determine if cA2 binds to transmembrane TNF-alpha and what effects such binding may have on TNF-alpha-expressing cells. A cell line expressing a cell-surface, mutant form of transmembrane TNF-alpha was prepared for these studies. Analysis of these TNF+ cells by flow cytometry, direct binding, and competitive binding assays showed that cA2 binds to the transmembrane form of TNF-alpha with high avidity. Binding of the IgG1 isotype of cA2, but not an IgG4 version of cA2, resulted in efficient killing of the TNF+ cells by both antibody-dependent cellular toxicity and complement-dependent cytotoxicity effector mechanisms. These findings indicate that, in addition to blocking soluble TNF-alpha activity, cA2 can bind to transmembrane TNF-alpha in vitro and suggest that cA2 binding may lead to lysis of TNF-alpha-expressing cells in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1043-4666
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
251-9
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions.
pubmed:affiliation
Department of Molecular Biology, Centocor, Inc., Malvern, PA 19355, USA.
pubmed:publicationType
Journal Article