Document Detail


From immunotoxins to immunoRNases.
MedLine Citation:
PMID:  18673286     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Immunotoxins are chimeric molecules that specifically target tumor cells, as they are made up of toxins linked to an antibody directed to a specific, cell-surface tumor-associated-antigen (TAA). When the immune moiety is internalized by the tumor cell, it will carry the conjugated toxin into the cell, so that the cell will be selectively killed in a way postulated more than a hundred years ago by Paul Ehrlich, the first author to use the term magic bullet. To date, toxicity and immunogenicity have complicated the clinical use of most immunotoxins. More recently, based on the immunotoxin principle, immunoRNases have been proposed, in which the toxin moiety of immunotoxins is replaced by a non-toxic RNase. An immunoRNase (IR) is in fact an immuno-pro-toxin, as it can travel in the bloodstream without any damages to cells devoid of the targeted TAA, while magically selecting the cells targeted by the immune moiety. Once internalized, the RNase moiety will exert its RNA degrading activity, which will readily lead to the death of the targeted cell. By choosing a human RNase, and a human antibody fragment as immune moiety, an IR would be not only non-toxic, but also non-immunogenic. As for the possible inhibitory action of the cytosolic RNase inhibitor, exerted on all non-toxic vertebrate RNases, it can be opposed by flooding the cytosol with high levels of IR, which will neutralize the RNase inhibitor, or by using RNases resistant to the inhibitor.
Authors:
Claudia De Lorenzo; Giuseppe D'Alessio
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current pharmaceutical biotechnology     Volume:  9     ISSN:  1873-4316     ISO Abbreviation:  Curr Pharm Biotechnol     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-08-04     Completed Date:  2008-10-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100960530     Medline TA:  Curr Pharm Biotechnol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  210-4     Citation Subset:  IM    
Affiliation:
Department of Structural and Functional Biology, University of Naples Federico II, Via Cintia, 80126 Naples, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Neoplasm / immunology
Cytosol / drug effects,  enzymology,  immunology,  metabolism
Humans
Immunotherapy
Immunotoxins* / immunology,  pharmacology,  therapeutic use
Models, Molecular
Neoplasms* / drug therapy,  immunology,  pathology
Protein Binding
Recombinant Fusion Proteins* / immunology,  pharmacology,  therapeutic use
Ribonucleases* / antagonists & inhibitors,  immunology,  pharmacology,  therapeutic use
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Immunotoxins; 0/Recombinant Fusion Proteins; EC 3.1.-/Ribonucleases

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