Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1993-5-6
|
| pubmed:abstractText |
We have previously shown that the recombinant single-chain immunotoxin anti-Tac(Fv)-PE40, composed of the variable domains of the anti-Tac monoclonal antibody in a single-chain form joined to a derivative of Pseudomonas exotoxin (PE), is cytotoxic toward malignant cells from adult T-cell leukemia (ATL) patients. Using this assay, we have now compared the activity of anti-Tac(Fv)-PE40 with that of an improved version, anti-Tac(Fv)-PE40KDEL which contains an altered carboxyl terminus, and also with two chimeric toxins made with diphtheria toxin (DT). One of these is a fusion of amino acids 1-388 of DT with anti-Tac(Fv) and is termed DT388-anti-Tac(Fv). The other, DT388-IL2, contains interleukin 2 (IL2) at the carboxyl terminus of the same DT derivative. We incubated these toxins with malignant ATL peripheral blood mononuclear cells (PBMCs) for 1-3 days and then measured [3H]leucine incorporation. We found that anti-Tac(Fv)-PE40KDEL was the most cytotoxic agent and was followed in decreasing order of activity by anti-Tac(Fv)-PE40, DT388-anti-Tac(Fv), and finally DT388-IL2. Trypan blue staining showed that inhibition of protein synthesis correlated with cell death. Time course studies showed that the recombinant toxins containing anti-Tac(Fv) were cytotoxic even if exposed to the cells for only one hour. After intravenous injection into mice, the half-life of anti-Tac(Fv)-PE40 or anti-Tac(Fv)-PE40KDEL was 30 minutes. Normal PBMCs were resistant to all four toxins. Recombinant immunotoxins made with anti-Tac merit further study as potential reagents in the treatment of ATL.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Diphtheria Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Endotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0887-6924
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
7
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
553-62
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8464234-Adult,
pubmed-meshheading:8464234-Animals,
pubmed-meshheading:8464234-Antibodies, Monoclonal,
pubmed-meshheading:8464234-Cytotoxicity, Immunologic,
pubmed-meshheading:8464234-Diphtheria Toxin,
pubmed-meshheading:8464234-Drug Screening Assays, Antitumor,
pubmed-meshheading:8464234-Endotoxins,
pubmed-meshheading:8464234-Female,
pubmed-meshheading:8464234-Humans,
pubmed-meshheading:8464234-Immunotoxins,
pubmed-meshheading:8464234-Interleukin-2,
pubmed-meshheading:8464234-Leukemia-Lymphoma, Adult T-Cell,
pubmed-meshheading:8464234-Lymphocytes,
pubmed-meshheading:8464234-Mice,
pubmed-meshheading:8464234-Mice, Inbred BALB C,
pubmed-meshheading:8464234-Pseudomonas,
pubmed-meshheading:8464234-Recombinant Fusion Proteins,
pubmed-meshheading:8464234-Time Factors,
pubmed-meshheading:8464234-Tumor Cells, Cultured
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Cytotoxic activities of recombinant immunotoxins composed of Pseudomonas toxin or diphtheria toxin toward lymphocytes from patients with adult T-cell leukemia.
|
| pubmed:affiliation |
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
|
| pubmed:publicationType |
Journal Article
|