| Specific targeting to murine myeloma cells of Cyt1Aa toxin from Bacillus thuringiensis subspecies israelensis. | |
| | |
MedLine Citation:
|
PMID: 17626007 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Multiple myeloma is currently an incurable cancer of plasma B cells often characterized by overproduction of abnormally high quantities of a patient-specific, clonotypic immunoglobulin "M-protein." The M-protein is expressed on the cell membrane and secreted into the blood. We previously showed that ligand-toxin conjugates (LTC) incorporating the ribosome-inactivating Ricin-A toxin were very effective in specific cytolysis of the anti-ligand antibody-bearing target cells used as models for multiple myeloma. Here, we report on the incorporation of the membrane-disruptive Cyt1Aa toxin from Bacillus thuringiensis subsp. israelensis into LTCs targeted to murine myeloma cells. Proteolytically activated Cyt1Aa was conjugated chemically or genetically through either its amino or carboxyl termini to the major peptidic epitope VHFFKNIVTPRTP (p87-99) of the myelin basic protein. The recombinant fusion-encoding genes were cloned and expressed in acrystalliferous B. thuringiensis subsp. israelensis through the shuttle vector pHT315. Both chemically conjugated and genetically fused LTCs were toxic to anti-myelin basic protein-expressing murine hybridoma cells, but the recombinant conjugates were more active. LTCs comprising the Cyt1Aa toxin might be useful anticancer agents. As a membrane-acting toxin, Cyt1Aa is not likely to induce development of resistant cell lines. |
| | |
Authors:
|
Shmuel Cohen; Rivka Cahan; Eitan Ben-Dov; Marina Nisnevitch; Arieh Zaritsky; Michael A Firer |
Related Documents
:
|
2558117 - Tetanus toxin as a marker for small-cell lung cancer cell lines. 17123907 - The contribution of cytolethal distending toxin to bacterial pathogenesis. 2122887 - Muscarinic cholinergic stimulation of inositol phosphate production in cultured embryon... 18776577 - Selective recovery of target cells employing a bi-functional aptamer. 22525867 - Enhancement of cisplatin cytotoxicity by benzyl isothiocyanate in hl-60 cells. 7011977 - Mannose-binding activity of escherichia coli: a determinant of attachment and ingestion... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-07-11 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 282 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2007 Sep |
Date Detail:
|
Created Date: 2007-09-24 Completed Date: 2007-11-08 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 28301-8 Citation Subset: IM |
Affiliation:
|
Department of Life Sciences, Ben-Gurion University of the Negev, P. O. 653, Be'er-Sheva 84105, Israel. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antibodies, Monoclonal / immunology Antineoplastic Agents / chemistry, immunology*, therapeutic use Bacillus thuringiensis / chemistry, genetics, immunology Bacterial Proteins / chemistry, genetics, immunology*, therapeutic use Bacterial Toxins / chemistry, genetics, immunology*, therapeutic use Cell Line, Tumor Drug Resistance, Neoplasm / immunology Endotoxins / chemistry, genetics, immunology*, therapeutic use Gene Expression Hemolysin Proteins / chemistry, genetics, immunology*, therapeutic use Hybridomas Immunotoxins / genetics, immunology*, therapeutic use Ligands Mice Models, Biological Multiple Myeloma / drug therapy, immunology* Myelin Basic Proteins / chemistry, genetics, immunology*, therapeutic use Myeloma Proteins / antagonists & inhibitors, genetics, immunology* Peptides / chemistry, genetics, immunology*, therapeutic use Recombinant Fusion Proteins / chemistry, genetics, immunology*, therapeutic use Ricin / chemistry, genetics, immunology, therapeutic use |
| Chemical | |
Reg. No./Substance:
|
0/Antibodies, Monoclonal; 0/Antineoplastic Agents; 0/Bacterial Proteins; 0/Bacterial Toxins; 0/Endotoxins; 0/Hemolysin Proteins; 0/Immunotoxins; 0/Ligands; 0/Myelin Basic Proteins; 0/Myeloma Proteins; 0/Peptides; 0/Recombinant Fusion Proteins; 0/insecticidal crystal protein, Bacillus Thuringiensis; 0/multiple myeloma M-proteins; 9009-86-3/Ricin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Transcriptional regulation of Bim by FoxO3A mediates hepatocyte lipoapoptosis.
Next Document: Biological heterogeneity of the peptide-binding motif of the 70-kDa heat shock protein by surface pl...