Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts

Tagging of RNases, such as the ribotoxin α-sarcin, with the variable domains of antibodies directed to surface antigens that are selectively expressed on tumor cells endows cellular specificity to their cytotoxic action. A recombinant single-chain immunotoxin based on the ribotoxin α-sarcin (IMTXA33...

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Autores: Tomé Amat, Jaime, Olombrada Sacristán, Miriam, Ruiz de la Herrán, Javier, Pérez Gómez, Eduardo, Andradas Arias, Clara, Sánchez García, María Cristina, Martínez, Leopoldo, Martínez Del Pozo, Álvaro, Gavilanes, José G., Lacadena García-Gallo, Francisco Javier
Formato: artículo
Fecha de publicación:2015
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/24531
Acesso em linha:https://hdl.handle.net/20.500.14352/24531
Access Level:acceso abierto
Palavra-chave:577.1
Immunotoxin
in vivo antitumor effectiveness
Colorectal cancer
GPA33
Ribotoxin α-sarcin
Inmunología
Bioquímica (Biología)
2412 Inmunología
2302 Bioquímica
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oai_identifier_str oai:docta.ucm.es:20.500.14352/24531
network_acronym_str ES
network_name_str España
repository_id_str
spelling Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenograftsTomé Amat, JaimeOlombrada Sacristán, MiriamRuiz de la Herrán, JavierPérez Gómez, EduardoAndradas Arias, ClaraSánchez García, María CristinaMartínez, LeopoldoMartínez Del Pozo, ÁlvaroGavilanes, José G.Lacadena García-Gallo, Francisco Javier577.1Immunotoxinin vivo antitumor effectivenessColorectal cancerGPA33Ribotoxin α-sarcinInmunologíaBioquímica (Biología)2412 Inmunología2302 BioquímicaTagging of RNases, such as the ribotoxin α-sarcin, with the variable domains of antibodies directed to surface antigens that are selectively expressed on tumor cells endows cellular specificity to their cytotoxic action. A recombinant single-chain immunotoxin based on the ribotoxin α-sarcin (IMTXA33αS), produced in the generally regarded as safe (GRAS) yeast Pichia pastoris, has been recently described as a promising candidate for the treatment of colorectal cancer cells expressing the glycoprotein A33 (GPA33) antigen, due to its high specific and effective cytotoxic effect on in vitro assays against targeted cells. Here we report the in vivo antitumor effectiveness of this immunotoxin on nude mice bearing GPA33-positive human colon cancer xenografts. Two sets of independent assays were performed, including three experimental groups: control (PBS) and treatment with two different doses of immunotoxin (50 or 100 μg/ injection) (n = 8). Intraperitoneal administration of IMTXA33αS resulted in significant dose-dependent tumor growth inhibition. In addition, the remaining tumors excised from immunotoxin-treated mice showed absence of the GPA33 antigen and a clear inhibition of angiogenesis and proliferative capacity. No signs of immunotoxin-induced pathological changes were observed from specimens tissues.Overall these results show efficient and selective cytotoxic action on tumor xenografts, combined with the lack of severe side effects, suggesting that IMTXA33αS is a potential therapeutic agent against colorectal cancer.ElsevierUniversidad Complutense de Madrid20152015-04-0120152015-04-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/24531reponame: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:20.500.14352/245312026-06-02T12:44:21Z
dc.title.none.fl_str_mv Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts
title Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts
spellingShingle Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts
Tomé Amat, Jaime
577.1
Immunotoxin
in vivo antitumor effectiveness
Colorectal cancer
GPA33
Ribotoxin α-sarcin
Inmunología
Bioquímica (Biología)
2412 Inmunología
2302 Bioquímica
title_short Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts
title_full Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts
title_fullStr Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts
title_full_unstemmed Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts
title_sort Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts
dc.creator.none.fl_str_mv Tomé Amat, Jaime
Olombrada Sacristán, Miriam
Ruiz de la Herrán, Javier
Pérez Gómez, Eduardo
Andradas Arias, Clara
Sánchez García, María Cristina
Martínez, Leopoldo
Martínez Del Pozo, Álvaro
Gavilanes, José G.
Lacadena García-Gallo, Francisco Javier
author Tomé Amat, Jaime
author_facet Tomé Amat, Jaime
Olombrada Sacristán, Miriam
Ruiz de la Herrán, Javier
Pérez Gómez, Eduardo
Andradas Arias, Clara
Sánchez García, María Cristina
Martínez, Leopoldo
Martínez Del Pozo, Álvaro
Gavilanes, José G.
Lacadena García-Gallo, Francisco Javier
author_role author
author2 Olombrada Sacristán, Miriam
Ruiz de la Herrán, Javier
Pérez Gómez, Eduardo
Andradas Arias, Clara
Sánchez García, María Cristina
Martínez, Leopoldo
Martínez Del Pozo, Álvaro
Gavilanes, José G.
Lacadena García-Gallo, Francisco Javier
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 577.1
Immunotoxin
in vivo antitumor effectiveness
Colorectal cancer
GPA33
Ribotoxin α-sarcin
Inmunología
Bioquímica (Biología)
2412 Inmunología
2302 Bioquímica
topic 577.1
Immunotoxin
in vivo antitumor effectiveness
Colorectal cancer
GPA33
Ribotoxin α-sarcin
Inmunología
Bioquímica (Biología)
2412 Inmunología
2302 Bioquímica
description Tagging of RNases, such as the ribotoxin α-sarcin, with the variable domains of antibodies directed to surface antigens that are selectively expressed on tumor cells endows cellular specificity to their cytotoxic action. A recombinant single-chain immunotoxin based on the ribotoxin α-sarcin (IMTXA33αS), produced in the generally regarded as safe (GRAS) yeast Pichia pastoris, has been recently described as a promising candidate for the treatment of colorectal cancer cells expressing the glycoprotein A33 (GPA33) antigen, due to its high specific and effective cytotoxic effect on in vitro assays against targeted cells. Here we report the in vivo antitumor effectiveness of this immunotoxin on nude mice bearing GPA33-positive human colon cancer xenografts. Two sets of independent assays were performed, including three experimental groups: control (PBS) and treatment with two different doses of immunotoxin (50 or 100 μg/ injection) (n = 8). Intraperitoneal administration of IMTXA33αS resulted in significant dose-dependent tumor growth inhibition. In addition, the remaining tumors excised from immunotoxin-treated mice showed absence of the GPA33 antigen and a clear inhibition of angiogenesis and proliferative capacity. No signs of immunotoxin-induced pathological changes were observed from specimens tissues.Overall these results show efficient and selective cytotoxic action on tumor xenografts, combined with the lack of severe side effects, suggesting that IMTXA33αS is a potential therapeutic agent against colorectal cancer.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-04-01
2015
2015-04-01
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/20.500.14352/24531
url https://hdl.handle.net/20.500.14352/24531
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 Elsevier
publisher.none.fl_str_mv Elsevier
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
_version_ 1869415781050089472
score 15,300719

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