Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-2
|
| pubmed:dateCreated |
1994-8-11
|
| pubmed:abstractText |
Interleukin 2 (IL2) receptors (IL2R's) are found on malignant cells in many human leukemias and lymphomas and are expressed by activated T cells in many autoimmune disorders. Anti-Tac(Fv), a single-chain protein composed of the variable heavy and light domains of the anti-IL2R monoclonal antibody anti-Tac, can be genetically fused to derivatives of Pseudomonas exotoxin (PE) or diphtheria toxin (DT) to form potent immunotoxins. We have shown that anti-Tac(Fv) binds to low affinity IL2R's on fresh chronic lymphocytic leukemia (CLL) and adult T-cell leukemia (ATL) cells and can target either toxin to kill those cells. Anti-Tac(Fv)-PE40, containing the truncated form of PE without its binding domain, was cytotoxic to malignant cells from 8 of 8 ATL patients tested, with IC50's ranging from 0.11 to 5.5 ng/ml. Anti-Tac(Fv)-PE40KDEL, a derivative of anti-Tac(Fv)-PE40 which contains the KDEL carboxyl terminus, was more cytotoxic toward cells from all ATL patients and also killed CLL cells from 8 of 16 patients. DT388-anti-Tac(Fv), containing amino acids 1-388 of DT fused to the amino terminus of anti-Tac(Fv), was less cytotoxic than anti-Tac(Fv)-PE40 on ATL cells from 4 of 5 patients, but was cytotoxic toward CLL cells from 12 of 16 patients. DT388-IL2, where IL2 is substituted for anti-Tac(Fv), is similar to DAB389IL2, an IL2-toxin currently in clinical trials. DT388-IL2 and DAB389IL2 differ by only a few amino acids and have equal cytotoxic activity. DT388-IL2 was cytotoxic toward ATL cells from all patients tested, but usually required much higher concentrations than anti-Tac(Fv)-PE40 and was poorly active against CLL cells. Thus, recombinant toxins containing anti-Tac(Fv) are cytotoxic toward freshly isolated CLL and ATL cells and will be studied further as potential therapy for IL2R-related disorders.
|
| 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/Diphtheria Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Exotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Heavy Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin mu-Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Immunotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors,
http://linkedlifedata.com/resource/pubmed/chemical/toxA protein, Pseudomonas aeruginosa
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
1042-8194
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
13
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1-10
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8025511-ADP Ribose Transferases,
pubmed-meshheading:8025511-Amino Acid Sequence,
pubmed-meshheading:8025511-Antibodies, Monoclonal,
pubmed-meshheading:8025511-Bacterial Toxins,
pubmed-meshheading:8025511-Cell Survival,
pubmed-meshheading:8025511-Diphtheria Toxin,
pubmed-meshheading:8025511-Exotoxins,
pubmed-meshheading:8025511-Humans,
pubmed-meshheading:8025511-Immunoglobulin Heavy Chains,
pubmed-meshheading:8025511-Immunoglobulin mu-Chains,
pubmed-meshheading:8025511-Immunotoxins,
pubmed-meshheading:8025511-Leukemia, B-Cell,
pubmed-meshheading:8025511-Leukemia, Lymphocytic, Chronic, B-Cell,
pubmed-meshheading:8025511-Leukemia, T-Cell,
pubmed-meshheading:8025511-Leukemia-Lymphoma, Adult T-Cell,
pubmed-meshheading:8025511-Molecular Sequence Data,
pubmed-meshheading:8025511-Receptors, Interleukin-2,
pubmed-meshheading:8025511-Recombinant Proteins,
pubmed-meshheading:8025511-Tumor Cells, Cultured,
pubmed-meshheading:8025511-Virulence Factors
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
Recombinant single-chain immunotoxins against T and B cell leukemias.
|
| pubmed:affiliation |
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
|
| pubmed:publicationType |
Journal Article,
Review
|