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

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...

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Authors: Ruiz-de-la-Herrán, Javier, Tomé-Amat, Jaime, Lázaro Gorines, Rodrigo, Gavilanes, José G., Lacadena García-Gallo, Francisco Javier
Format: article
Publication Date:2019
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/12352
Online Access:https://hdl.handle.net/20.500.14352/12352
Access Level:Open access
Keyword:576
577.1
616-006
immunotoxin
ribotoxin
α-sarcin
RNase T1
furin
intracellular trafficking
colorectal cancer
Oncología
Biología celular (Biología)
Bioquímica (Biología)
3201.01 Oncología
2407 Biología Celular
2302 Bioquímica
id ES_a7a9bae366ab7f66e3cd4fdd05b526cb
oai_identifier_str oai:docta.ucm.es:20.500.14352/12352
network_acronym_str ES
network_name_str España
repository_id_str
spelling Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based ImmunotoxinsRuiz-de-la-Herrán, JavierTomé-Amat, JaimeLázaro Gorines, RodrigoGavilanes, José G.Lacadena García-Gallo, Francisco Javier576577.1616-006immunotoxinribotoxinα-sarcinRNase T1furinintracellular traffickingcolorectal cancerOncologíaBiología celular (Biología)Bioquímica (Biología)3201.01 Oncología2407 Biología Celular2302 BioquímicaImmunotoxins 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.mdpiUniversidad Complutense de Madrid20192019-10-1220192019-10-12journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/12352reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/123522026-06-02T12:44:21Z
dc.title.none.fl_str_mv Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins
title Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins
spellingShingle 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
576
577.1
616-006
immunotoxin
ribotoxin
α-sarcin
RNase T1
furin
intracellular trafficking
colorectal cancer
Oncología
Biología celular (Biología)
Bioquímica (Biología)
3201.01 Oncología
2407 Biología Celular
2302 Bioquímica
title_short Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins
title_full Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins
title_fullStr Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins
title_full_unstemmed Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins
title_sort Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins
dc.creator.none.fl_str_mv Ruiz-de-la-Herrán, Javier
Tomé-Amat, Jaime
Lázaro Gorines, Rodrigo
Gavilanes, José G.
Lacadena García-Gallo, Francisco Javier
author Ruiz-de-la-Herrán, Javier
author_facet Ruiz-de-la-Herrán, Javier
Tomé-Amat, Jaime
Lázaro Gorines, Rodrigo
Gavilanes, José G.
Lacadena García-Gallo, Francisco Javier
author_role author
author2 Tomé-Amat, Jaime
Lázaro Gorines, Rodrigo
Gavilanes, José G.
Lacadena García-Gallo, Francisco Javier
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 576
577.1
616-006
immunotoxin
ribotoxin
α-sarcin
RNase T1
furin
intracellular trafficking
colorectal cancer
Oncología
Biología celular (Biología)
Bioquímica (Biología)
3201.01 Oncología
2407 Biología Celular
2302 Bioquímica
topic 576
577.1
616-006
immunotoxin
ribotoxin
α-sarcin
RNase T1
furin
intracellular trafficking
colorectal cancer
Oncología
Biología celular (Biología)
Bioquímica (Biología)
3201.01 Oncología
2407 Biología Celular
2302 Bioquímica
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-10-12
2019
2019-10-12
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/12352
url https://hdl.handle.net/20.500.14352/12352
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv mdpi
publisher.none.fl_str_mv mdpi
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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