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Ruiz de la Herrán, Javier, Tomé Amat, Jaime, Lázaro Gorines, Rodrigo, Gavilanes Franco, José Gregorio and Lacadena García-Gallo, Javier (2019). Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins. "Toxins", v. 11 (n. 10); p. 593. ISSN 2072-6651. https://doi.org/10.3390/toxins11100593.
Title: | Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins |
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Author/s: |
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Item Type: | Article |
Título de Revista/Publicación: | Toxins |
Date: | October 2019 |
ISSN: | 2072-6651 |
Volume: | 11 |
Subjects: | |
Freetext Keywords: | immunotoxin; ribotoxin; α-sarcin; RNase T1; furin; intracellular trafficking; colorectal cancer |
Faculty: | Centro de Investigación en Biotecnología y Genómica de Plantas (CBGP) (UPM) |
Department: | Biotecnología - Biología Vegetal |
Creative Commons Licenses: | Recognition - No derivative works - Non commercial |
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Immunotoxins are chimeric molecules that combine the specificity of an antibody to recognize and bind tumor antigens with the potency of the enzymatic activity of a toxin, thus, promoting the death of target cells. Among them, RNases-based immunotoxins have arisen as promising antitumor therapeutic agents. In this work, we describe the production and purification of two new immunoconjugates, based on RNase T1 and the fungal ribotoxin α-sarcin, with optimized properties for tumor treatment due to the inclusion of a furin cleavage site. Circular dichroism spectroscopy, ribonucleolytic activity studies, flow cytometry, fluorescence microscopy, and cell viability assays were carried out for structural and in vitro functional characterization. Our results confirm the enhanced antitumor efficiency showed by these furin-immunotoxin variants as a result of an improved release of their toxic domain to the cytosol, favoring the accessibility of both ribonucleases to their substrates. Overall, these results represent a step forward in the design of immunotoxins with optimized properties for potential therapeutic application in vivo.
Item ID: | 63636 |
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DC Identifier: | https://oa.upm.es/63636/ |
OAI Identifier: | oai:oa.upm.es:63636 |
DOI: | 10.3390/toxins11100593 |
Official URL: | https://www.mdpi.com/2072-6651/11/10/593 |
Deposited by: | Memoria Investigacion |
Deposited on: | 10 Dec 2020 08:17 |
Last Modified: | 30 Nov 2022 09:00 |