Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins

Ruiz de la Herrán, Javier and Tomé Amat, Jaime and Lázaro Gorines, Rodrigo and 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.

Description

Title: Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins
Author/s:
  • Ruiz de la Herrán, Javier
  • Tomé Amat, Jaime
  • Lázaro Gorines, Rodrigo
  • Gavilanes Franco, José Gregorio
  • Lacadena García-Gallo, Javier
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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Abstract

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.

Funding Projects

TypeCodeAcronymLeaderTitle
Government of SpainRD16/0006/0003UnspecifiedDíaz Perales, AraceliUnspecified
Government of SpainRD16/0006/0013UnspecifiedCuesta Herranz, JavierUnspecified
Government of SpainRD16/0006/0015UnspecifiedBarber Hernández, DomingoUnspecified

More information

Item ID: 63636
DC Identifier: http://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: 10 Dec 2020 08:17
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