Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1995-10-19
|
| pubmed:abstractText |
A fusion protein was synthesized consisting of the murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) gene spliced to a truncated form of the diphtheria toxin (DT390) gene coding for a molecule that retained full enzymatic activity, but excluded the native binding domain. The DT390-mGM-CSF hybrid gene was cloned into a vector under the control of an inducible promoter and the protein expressed in Escherichia coli. After induction, a protein was purified from inclusion bodies in accord with the deduced molecular weight of DT390 mGM-CSF. Cell-free studies of the adenosine diphosphate-ribosylating activity of DT390 mGM-CSF showed results that were similar to those of native DT. The DT390 mGM-CSF immunotoxin inhibited FDCP2.1d, a murine myelomonocytic tumor line expressing the GM-CSF receptor with an IC50 (concentration inhibiting 50% activity) of 5 x 10(-11) mol/L. The fusion toxin was specifically cytotoxic and directed by the GM-CSF portion of the molecule because addition of a monoclonal antibody directed against GM-CSF inhibited its ability to kill the cell line. Cell lines that do not express GM-CSF receptor were not inhibited by the fusion toxin. DT390 mGM-CSF was also able to specifically inhibit normal committed bone marrow (BM) progenitor cells as measured in clonal colony-forming unit granulocyte-macrophage assays. Together, these findings indicate that DT390 mGM-CSF may be useful as a novel tool for purging BM of contaminating leukemia cells or in vivo for eliminating residual leukemia cells. Also, it can be used to determine whether committed and/or noncommitted BM progenitor cells express the GM-CSF receptor.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Diphtheria Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0006-4971
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
86
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2732-40
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:7670112-Amino Acid Sequence,
pubmed-meshheading:7670112-Animals,
pubmed-meshheading:7670112-Antineoplastic Agents,
pubmed-meshheading:7670112-Base Sequence,
pubmed-meshheading:7670112-Binding Sites,
pubmed-meshheading:7670112-Bone Marrow Cells,
pubmed-meshheading:7670112-Cell Death,
pubmed-meshheading:7670112-Cell Line,
pubmed-meshheading:7670112-Colony-Forming Units Assay,
pubmed-meshheading:7670112-Diphtheria Toxin,
pubmed-meshheading:7670112-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:7670112-Granulocytes,
pubmed-meshheading:7670112-Hematopoietic Stem Cells,
pubmed-meshheading:7670112-Mice,
pubmed-meshheading:7670112-Molecular Sequence Data,
pubmed-meshheading:7670112-Monocytes,
pubmed-meshheading:7670112-Receptors, Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:7670112-Recombinant Fusion Proteins
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
A murine cytokine fusion toxin specifically targeting the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor on normal committed bone marrow progenitor cells and GM-CSF-dependent tumor cells.
|
| pubmed:affiliation |
Department of Therapeutic Radiology, University of Minnesota Hospital and Clinics, Minneapolis 55455, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|