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T-cell co-stimulatory blockade in kidney transplantation: back to the bench

It is believed that blocking positive T-cell co-stimulatory pathways should lead to long-term graft acceptance. Despite the exciting initial achievements in experimental animal models, targeting co-stimulatory pathways has shown to be much more complex in the clinic. In addition to multiple binding...

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Detalles Bibliográficos
Autores principales: Riella, Leonardo V, Sayegh, Mohamed H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089598/
https://www.ncbi.nlm.nih.gov/pubmed/25018899
http://dx.doi.org/10.1038/kisup.2011.8
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author Riella, Leonardo V
Sayegh, Mohamed H
author_facet Riella, Leonardo V
Sayegh, Mohamed H
author_sort Riella, Leonardo V
collection PubMed
description It is believed that blocking positive T-cell co-stimulatory pathways should lead to long-term graft acceptance. Despite the exciting initial achievements in experimental animal models, targeting co-stimulatory pathways has shown to be much more complex in the clinic. In addition to multiple binding partners, some co-stimulatory interactions have been found to be inhibitory in nature, whereas others were demonstrated to be important in the development of regulatory T cells. Moreover, memory T cells have been shown to be resistant to co-stimulation blockade. Herein we focus on the B7:CD28 pathway and describe the evolution of targeting this pathway with cytotoxic T-lymphocyte antigen-4-Ig from bench to clinic. We also attempt to address possible causes for the unexpected high rejection rate observed in the phase III clinical trials with belatacept, using experimental data obtained from basic science research.
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spelling pubmed-40895982014-07-11 T-cell co-stimulatory blockade in kidney transplantation: back to the bench Riella, Leonardo V Sayegh, Mohamed H Kidney Int Suppl (2011) Meeting Report It is believed that blocking positive T-cell co-stimulatory pathways should lead to long-term graft acceptance. Despite the exciting initial achievements in experimental animal models, targeting co-stimulatory pathways has shown to be much more complex in the clinic. In addition to multiple binding partners, some co-stimulatory interactions have been found to be inhibitory in nature, whereas others were demonstrated to be important in the development of regulatory T cells. Moreover, memory T cells have been shown to be resistant to co-stimulation blockade. Herein we focus on the B7:CD28 pathway and describe the evolution of targeting this pathway with cytotoxic T-lymphocyte antigen-4-Ig from bench to clinic. We also attempt to address possible causes for the unexpected high rejection rate observed in the phase III clinical trials with belatacept, using experimental data obtained from basic science research. Nature Publishing Group 2011-08 2011-07-15 /pmc/articles/PMC4089598/ /pubmed/25018899 http://dx.doi.org/10.1038/kisup.2011.8 Text en Copyright © 2011 International Society of Nephrology
spellingShingle Meeting Report
Riella, Leonardo V
Sayegh, Mohamed H
T-cell co-stimulatory blockade in kidney transplantation: back to the bench
title T-cell co-stimulatory blockade in kidney transplantation: back to the bench
title_full T-cell co-stimulatory blockade in kidney transplantation: back to the bench
title_fullStr T-cell co-stimulatory blockade in kidney transplantation: back to the bench
title_full_unstemmed T-cell co-stimulatory blockade in kidney transplantation: back to the bench
title_short T-cell co-stimulatory blockade in kidney transplantation: back to the bench
title_sort t-cell co-stimulatory blockade in kidney transplantation: back to the bench
topic Meeting Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089598/
https://www.ncbi.nlm.nih.gov/pubmed/25018899
http://dx.doi.org/10.1038/kisup.2011.8
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