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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
47
|
| pubmed:dateCreated |
1996-1-17
|
| pubmed:abstractText |
Diphtheria toxin (DT) is often used in the construction of immunotoxins. One potential problem using DT-based immunotoxins is the pre-existing anti-DT antibodies present in human blood due to vaccination. The present study examined the effect of human serum with pre-existing anti-DT antibodies on the toxicity of UCHT1-CRM9, an immunotoxin directed against CD3 molecules on T-lymphocytes. Sera with detectable anti-DT antibodies at 1:100 or greater dilutions inhibited the immunotoxin toxicity. Experiments with radio-labeled UCHT1-CRM9 indicate that anti-DT antibodies partially block its binding to the cell surface as well as inhibit the translocation from the endosome to the cytosol. The inhibitory effect could be adsorbed using a full-length DT mutant or B-subfragment. A C-terminal truncation mutant could not adsorb the inhibitory effect, suggesting that the last 150 amino acids contain the epitope(s) recognized by the inhibitory antibodies. Therefore, an anti-CD3 single-chain immunotoxin, sFv-DT390, was made with a truncated DT. The IC50 of sFv-DT390 was 4.8 x 10(-11) M, 1/16 the potency of the divalent UCHT1-CRM9. More importantly, sFv-DT390 toxicity was only slightly affected by the anti-DT antibodies in human sera.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Bacterial,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Diphtheria Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Immunotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Leucine,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
24
|
| pubmed:volume |
270
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
28037-41
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:7499288-Antibodies, Bacterial,
pubmed-meshheading:7499288-Antigens, CD3,
pubmed-meshheading:7499288-Cell Line,
pubmed-meshheading:7499288-Cytosol,
pubmed-meshheading:7499288-Diphtheria Toxin,
pubmed-meshheading:7499288-Dose-Response Relationship, Drug,
pubmed-meshheading:7499288-Endocytosis,
pubmed-meshheading:7499288-Endosomes,
pubmed-meshheading:7499288-Epitopes,
pubmed-meshheading:7499288-Humans,
pubmed-meshheading:7499288-Immunotoxins,
pubmed-meshheading:7499288-Kinetics,
pubmed-meshheading:7499288-Leucine,
pubmed-meshheading:7499288-Mutagenesis, Site-Directed,
pubmed-meshheading:7499288-Point Mutation,
pubmed-meshheading:7499288-Protein Biosynthesis,
pubmed-meshheading:7499288-Recombinant Proteins,
pubmed-meshheading:7499288-T-Lymphocytes,
pubmed-meshheading:7499288-Vaccination
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
An anti-CD3 single-chain immunotoxin with a truncated diphtheria toxin avoids inhibition by pre-existing antibodies in human blood.
|
| pubmed:affiliation |
Section on Biophysical Chemistry, National Institute of Mental Health, Bethesda, Maryland 28092-4034, USA.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|