Document Detail


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
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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.
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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

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