Abstract
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.
Keywords: Immunotoxins, immunoRNases, immunotherapy
Current Pharmaceutical Biotechnology
Title: From ImmunoToxins to ImmunoRNases
Volume: 9 Issue: 3
Author(s): Claudia De Lorenzo and Giuseppe D'Alessio
Affiliation:
Keywords: Immunotoxins, immunoRNases, immunotherapy
Abstract: 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.
Export Options
About this article
Cite this article as:
Lorenzo De Claudia and D'Alessio Giuseppe, From ImmunoToxins to ImmunoRNases, Current Pharmaceutical Biotechnology 2008; 9 (3) . https://dx.doi.org/10.2174/138920108784567254
DOI https://dx.doi.org/10.2174/138920108784567254 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Metaboloepigenetic Dimension of Cancer Stem Cells: Evaluating the Market Potential for New Metabostemness-Targeting Oncology Drugs
Current Pharmaceutical Design MicroRNAs in Chronic Lymphocytic Leukemia: An Old Disease with New Genetic Insights
MicroRNA Promising Chemoprevention of Colonic Aberrant Crypt Foci by <i>Portunus segnis</i> Muscle and Shell Extracts in Azoxymethane-Induced Colorectal Cancer in Rats
Anti-Cancer Agents in Medicinal Chemistry Synthesis and Preliminary Biological Evaluation of Polyamine-aniline Acridines as P-glycoprotein Inhibitors
Medicinal Chemistry Molecular and Cellular Regulators of Cancer Angiogenesis
Current Cancer Drug Targets Antifungal Drug Discovery, Six New Molecules Patented After 10 Years of Feast:Why do we Need New Patented Drugs Apart from New Strategies?
Recent Patents on Anti-Infective Drug Discovery Understanding Cancer Drug Resistance by Developing and Studying Resistant Cell Line Models
Current Cancer Drug Targets New Use for Old Drugs? Prospective Targets of Chloroquines in Cancer Therapy
Current Drug Targets Rituximab Therapy and Autoimmune Disease
Current Immunology Reviews (Discontinued) Protein Kinase B/AKT and Focal Adhesion Kinase: Two Close Signaling Partners in Cancer
Anti-Cancer Agents in Medicinal Chemistry T Lymphocytes as Targets of Gene Transfer with Moloney-Type Retroviral Vectors
Current Gene Therapy Safety of Multi-Targeted Kinase Inhibitors as Monotherapy Treatment of Cancer: A Systematic Review of the Literature
Current Drug Safety Carcinogenicity and Chronic Rodent Toxicity of the Selective Progesterone Receptor Modulator Ulipristal Acetate
Current Drug Safety Haematopoietic Stem Cell Gene Therapy to Treat Autoimmune Disease
Current Stem Cell Research & Therapy CAM Use in Pediatric Oncology
Current Pediatric Reviews Clinical Applications of the Urokinase Receptor (uPAR) for Cancer Patients
Current Pharmaceutical Design Acute Hypersensitivity Reactions to Chemotherapy Agents: An Overview
Inflammation & Allergy - Drug Targets (Discontinued) Rho-Signaling Pathways in Chronic Myelogenous Leukemia
Cardiovascular & Hematological Disorders-Drug Targets MicroRNA Regulation of Programmed Cell Death Pathways in Cancer
Current Chemical Biology Editorial [Hot topic: Selected New Developments in Oncology (Guest Editors: Jos H. Beijnen and Jan H.M. Schellens)]
Current Clinical Pharmacology