Abrin immunotoxin: targeted cytotoxicity and intracellular trafficking pathway.

<h4>Background</h4>Immunotherapy is fast emerging as one of the leading modes of treatment of cancer, in combination with chemotherapy and radiation. Use of immunotoxins, proteins bearing a cell-surface receptor-specific antibody conjugated to a toxin, enhances the efficacy of cancer tre...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sudarshan Gadadhar, Anjali A Karande
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b93e05693f543eabe8ea49173930657
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2b93e05693f543eabe8ea49173930657
record_format	dspace
spelling	oai:doaj.org-article:2b93e05693f543eabe8ea491739306572021-11-18T07:54:49ZAbrin immunotoxin: targeted cytotoxicity and intracellular trafficking pathway.1932-620310.1371/journal.pone.0058304https://doaj.org/article/2b93e05693f543eabe8ea491739306572013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23472175/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Immunotherapy is fast emerging as one of the leading modes of treatment of cancer, in combination with chemotherapy and radiation. Use of immunotoxins, proteins bearing a cell-surface receptor-specific antibody conjugated to a toxin, enhances the efficacy of cancer treatment. The toxin Abrin, isolated from the Abrus precatorius plant, is a type II ribosome inactivating protein, has a catalytic efficiency higher than any other toxin belonging to this class of proteins but has not been exploited much for use in targeted therapy.<h4>Methods</h4>Protein synthesis assay using (3)[H] L-leucine incorporation; construction and purification of immunotoxin; study of cell death using flow cytometry; confocal scanning microscopy and sub-cellular fractionation with immunoblot analysis of localization of proteins.<h4>Results</h4>We used the recombinant A chain of abrin to conjugate to antibodies raised against the human gonadotropin releasing hormone receptor. The conjugate inhibited protein synthesis and also induced cell death specifically in cells expressing the receptor. The conjugate exhibited differences in the kinetics of inhibition of protein synthesis, in comparison to abrin, and this was attributed to differences in internalization and trafficking of the conjugate within the cells. Moreover, observations of sequestration of the A chain into the nucleus of cells treated with abrin but not in cells treated with the conjugate reveal a novel pathway for the movement of the conjugate in the cells.<h4>Conclusions</h4>This is one of the first reports on nuclear localization of abrin, a type II RIP. The immunotoxin mAb F1G4-rABRa-A, generated in our laboratory, inhibits protein synthesis specifically on cells expressing the gonadotropin releasing hormone receptor and the pathway of internalization of the protein is distinct from that seen for abrin.Sudarshan GadadharAnjali A KarandePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58304 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sudarshan Gadadhar Anjali A Karande Abrin immunotoxin: targeted cytotoxicity and intracellular trafficking pathway.
description	<h4>Background</h4>Immunotherapy is fast emerging as one of the leading modes of treatment of cancer, in combination with chemotherapy and radiation. Use of immunotoxins, proteins bearing a cell-surface receptor-specific antibody conjugated to a toxin, enhances the efficacy of cancer treatment. The toxin Abrin, isolated from the Abrus precatorius plant, is a type II ribosome inactivating protein, has a catalytic efficiency higher than any other toxin belonging to this class of proteins but has not been exploited much for use in targeted therapy.<h4>Methods</h4>Protein synthesis assay using (3)[H] L-leucine incorporation; construction and purification of immunotoxin; study of cell death using flow cytometry; confocal scanning microscopy and sub-cellular fractionation with immunoblot analysis of localization of proteins.<h4>Results</h4>We used the recombinant A chain of abrin to conjugate to antibodies raised against the human gonadotropin releasing hormone receptor. The conjugate inhibited protein synthesis and also induced cell death specifically in cells expressing the receptor. The conjugate exhibited differences in the kinetics of inhibition of protein synthesis, in comparison to abrin, and this was attributed to differences in internalization and trafficking of the conjugate within the cells. Moreover, observations of sequestration of the A chain into the nucleus of cells treated with abrin but not in cells treated with the conjugate reveal a novel pathway for the movement of the conjugate in the cells.<h4>Conclusions</h4>This is one of the first reports on nuclear localization of abrin, a type II RIP. The immunotoxin mAb F1G4-rABRa-A, generated in our laboratory, inhibits protein synthesis specifically on cells expressing the gonadotropin releasing hormone receptor and the pathway of internalization of the protein is distinct from that seen for abrin.
format	article
author	Sudarshan Gadadhar Anjali A Karande
author_facet	Sudarshan Gadadhar Anjali A Karande
author_sort	Sudarshan Gadadhar
title	Abrin immunotoxin: targeted cytotoxicity and intracellular trafficking pathway.
title_short	Abrin immunotoxin: targeted cytotoxicity and intracellular trafficking pathway.
title_full	Abrin immunotoxin: targeted cytotoxicity and intracellular trafficking pathway.
title_fullStr	Abrin immunotoxin: targeted cytotoxicity and intracellular trafficking pathway.
title_full_unstemmed	Abrin immunotoxin: targeted cytotoxicity and intracellular trafficking pathway.
title_sort	abrin immunotoxin: targeted cytotoxicity and intracellular trafficking pathway.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/2b93e05693f543eabe8ea49173930657
work_keys_str_mv	AT sudarshangadadhar abrinimmunotoxintargetedcytotoxicityandintracellulartraffickingpathway AT anjaliakarande abrinimmunotoxintargetedcytotoxicityandintracellulartraffickingpathway
_version_	1718422775641669632

Abrin immunotoxin: targeted cytotoxicity and intracellular trafficking pathway.

Ejemplares similares