From ImmunoToxins to ImmunoRNases
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.
Document Type: Research Article
Publication date: June 1, 2008
More about this publication?
- Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.