Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
1994-7-12
|
| pubmed:abstractText |
We have produced a single plasmid encoding both the heavy chain Fd domain (VH + CH1) of the anti-interleukin-2 receptor (IL2R) monoclonal antibody anti-Tac, and the anti-Tac light chain fused to PE40, a truncated derivative of Pseudomonas exotoxin. The active immunotoxin anti-Tac(Fab)-PE40 could be recovered from E. coli from either periplasm or renatured inclusion bodies. The double-chain immunotoxin was very cytotoxic toward IL2R-bearing cell lines, human activated T cells and fresh adult-T-cell-leukemia cells. The cytotoxicity was similar to that of anti-Tac(Fv)-PE40, the single-chain recombinant toxin containing only the variable domains of anti-Tac. IL2R-binding affinity was also equivalent to that of anti-Tac(Fv)-PE40, which is one-third that of anti-Tac. The serum half-life in mice was significantly prolonged as compared with anti-Tac(Fv)-PE40, with a beta phase of 430 vs. 57 minutes, but the LD50s were equivalent when the immunotoxins were administered in 3 daily doses. Anti-Tac(Fab)-PE40 was very cytotoxic in vitro toward transfected ATAC-4 carcinoma cells which express IL2Rs. In mice bearing ATAC-4 tumors, anti-Tac(Fab)-PE40 showed significant anti-tumor activity, inducing complete remissions in 80 and 100% of treated animals at approximately 7 and 14% respectively of the LD50. Anti-Tac(Fab)-PE40 was much more effective in vitro and in vivo than chemical conjugates between anti-Tac and truncated PE molecules. The recombinant Fab toxin should be studied further as potential treatment for IL2R-related malignancies, particularly if smaller recombinant immunotoxins have insufficient half-life in humans.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ADP Ribose Transferases,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Exotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors,
http://linkedlifedata.com/resource/pubmed/chemical/toxA protein, Pseudomonas aeruginosa
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0020-7136
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
57
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
856-64
|
| pubmed:dateRevised |
2007-7-24
|
| pubmed:meshHeading |
pubmed-meshheading:8206679-ADP Ribose Transferases,
pubmed-meshheading:8206679-Animals,
pubmed-meshheading:8206679-Antibodies, Monoclonal,
pubmed-meshheading:8206679-Bacterial Toxins,
pubmed-meshheading:8206679-Base Sequence,
pubmed-meshheading:8206679-Exotoxins,
pubmed-meshheading:8206679-Humans,
pubmed-meshheading:8206679-Immunotoxins,
pubmed-meshheading:8206679-Mice,
pubmed-meshheading:8206679-Mice, Nude,
pubmed-meshheading:8206679-Molecular Sequence Data,
pubmed-meshheading:8206679-Neoplasm Transplantation,
pubmed-meshheading:8206679-Neoplasms, Experimental,
pubmed-meshheading:8206679-Oligodeoxyribonucleotides,
pubmed-meshheading:8206679-Receptors, Interleukin-2,
pubmed-meshheading:8206679-Recombinant Fusion Proteins,
pubmed-meshheading:8206679-Transplantation, Heterologous,
pubmed-meshheading:8206679-Tumor Cells, Cultured,
pubmed-meshheading:8206679-Virulence Factors
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
Anti-Tac(Fab)-PE40, a recombinant double-chain immunotoxin which kills interleukin-2-receptor-bearing cells and induces complete remission in an in vivo tumor model.
|
| pubmed:affiliation |
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
|
| pubmed:publicationType |
Journal Article
|