Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
|
| pubmed:dateCreated |
1992-11-13
|
| pubmed:abstractText |
Mik-beta 1 is a mAb that binds to the beta subunit of the IL-2R. We have constructed a recombinant single chain immunotoxin Mik-beta 1(Fv)-PE40 by genetically fusing the H and L V domains of Mik-beta 1 to each other via a peptide linker, and then to PE40, a derivative of Pseudomonas exotoxin. Mik-beta 1(Fv)-PE40 was selectively cytotoxic for cells expressing high levels of IL-2R beta (p75) subunit. Mik-beta 1(Fv)-PE40 was cytotoxic to the NK cell line YT-S, which expresses p75 but not p55 subunits, with an IC50 of 6 ng/ml. The ATL line HUT-102 was less sensitive, with an IC50 of 200 ng/ml. However, the IC50 could be lowered to 11 ng/ml when Mik-beta 1(Fv)-PE40 was allowed to bind to HUT-102 cells at 4 degrees C for 4 h before overnight incubation at 37 degrees C. An excess of Mik-beta 1 but not of anti-Tac, the anti-p55 mAb, prevented the cytotoxicity of Mik-beta 1(Fv)-PE40. We constructed a more active version of Mik-beta 1(Fv)-PE40, designated Mik-beta 1(Fv)-PE40KDEL, by converting the carboxyl-terminus of the toxin from -REDLK to -KDEL. Mik-beta 1(Fv)-PE40KDEL showed an IC50 of 2 ng/ml toward YT-S cells and 35 ng/ml toward HUT-102 cells. Binding studies using radioiodinated Mik-beta 1 showed that Mik-beta 1(Fv)-PE40 bound to the p75 receptor subunit with 11% of the affinity of the native Mik-beta 1 antibody. Mik-beta 1(Fv)-PE40 may be a useful reagent to study cells that express IL-2R, and it deserves further study as a possible treatment for cancers in which the malignant cells express high numbers of p75 subunit.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ADP Ribose Transferases,
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/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 |
Oct
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
149
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2810-5
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:1401913-ADP Ribose Transferases,
pubmed-meshheading:1401913-Amino Acid Sequence,
pubmed-meshheading:1401913-Bacterial Toxins,
pubmed-meshheading:1401913-Base Sequence,
pubmed-meshheading:1401913-Cell Line,
pubmed-meshheading:1401913-Exotoxins,
pubmed-meshheading:1401913-Humans,
pubmed-meshheading:1401913-Immunotoxins,
pubmed-meshheading:1401913-Molecular Sequence Data,
pubmed-meshheading:1401913-Protein Biosynthesis,
pubmed-meshheading:1401913-Receptors, Interleukin-2,
pubmed-meshheading:1401913-Recombinant Proteins,
pubmed-meshheading:1401913-Temperature,
pubmed-meshheading:1401913-Virulence Factors
|
| pubmed:year |
1992
|
| pubmed:articleTitle |
Mik-beta 1(Fv)-PE40, a recombinant immunotoxin cytotoxic toward cells bearing the beta-chain of the IL-2 receptor.
|
| pubmed:affiliation |
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
|
| pubmed:publicationType |
Journal Article
|