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Current State of Type 1 Diabetes Immunotherapy: Incremental Advances, Huge Leaps, or More of the Same?

Thus far, none of the preclinically successful and promising immunomodulatory agents for type 1 diabetes mellitus (T1DM) has conferred stable, long-term insulin independence to diabetic patients. The majority of these immunomodulators are humanised antibodies that target immune cells or cytokines. T...

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Detalles Bibliográficos
Autores principales: Phillips, Brett, Trucco, Massimo, Giannoukakis, Nick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139873/
https://www.ncbi.nlm.nih.gov/pubmed/21785616
http://dx.doi.org/10.1155/2011/432016
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author Phillips, Brett
Trucco, Massimo
Giannoukakis, Nick
author_facet Phillips, Brett
Trucco, Massimo
Giannoukakis, Nick
author_sort Phillips, Brett
collection PubMed
description Thus far, none of the preclinically successful and promising immunomodulatory agents for type 1 diabetes mellitus (T1DM) has conferred stable, long-term insulin independence to diabetic patients. The majority of these immunomodulators are humanised antibodies that target immune cells or cytokines. These as well as fusion proteins and inhibitor proteins all share varying adverse event occurrence and severity. Other approaches have included intact putative autoantigens or autoantigen peptides. Considerable logistical outlays have been deployed to develop and to translate humanised antibodies targeting immune cells, cytokines, and cytokine receptors to the clinic. Very recent phase III trials with the leading agent, a humanised anti-CD3 antibody, call into question whether further development of these biologics represents a step forward or more of the same. Combination therapies of one or more of these humanised antibodies are also being considered, and they face identical, if not more serious, impediments and safety issues. This paper will highlight the preclinical successes and the excitement generated by phase II trials while offering alternative possibilities and new translational avenues that can be explored given the very recent disappointment in leading agents in more advanced clinical trials.
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spelling pubmed-31398732011-07-22 Current State of Type 1 Diabetes Immunotherapy: Incremental Advances, Huge Leaps, or More of the Same? Phillips, Brett Trucco, Massimo Giannoukakis, Nick Clin Dev Immunol Review Article Thus far, none of the preclinically successful and promising immunomodulatory agents for type 1 diabetes mellitus (T1DM) has conferred stable, long-term insulin independence to diabetic patients. The majority of these immunomodulators are humanised antibodies that target immune cells or cytokines. These as well as fusion proteins and inhibitor proteins all share varying adverse event occurrence and severity. Other approaches have included intact putative autoantigens or autoantigen peptides. Considerable logistical outlays have been deployed to develop and to translate humanised antibodies targeting immune cells, cytokines, and cytokine receptors to the clinic. Very recent phase III trials with the leading agent, a humanised anti-CD3 antibody, call into question whether further development of these biologics represents a step forward or more of the same. Combination therapies of one or more of these humanised antibodies are also being considered, and they face identical, if not more serious, impediments and safety issues. This paper will highlight the preclinical successes and the excitement generated by phase II trials while offering alternative possibilities and new translational avenues that can be explored given the very recent disappointment in leading agents in more advanced clinical trials. Hindawi Publishing Corporation 2011 2011-07-18 /pmc/articles/PMC3139873/ /pubmed/21785616 http://dx.doi.org/10.1155/2011/432016 Text en Copyright © 2011 Brett Phillips et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Phillips, Brett
Trucco, Massimo
Giannoukakis, Nick
Current State of Type 1 Diabetes Immunotherapy: Incremental Advances, Huge Leaps, or More of the Same?
title Current State of Type 1 Diabetes Immunotherapy: Incremental Advances, Huge Leaps, or More of the Same?
title_full Current State of Type 1 Diabetes Immunotherapy: Incremental Advances, Huge Leaps, or More of the Same?
title_fullStr Current State of Type 1 Diabetes Immunotherapy: Incremental Advances, Huge Leaps, or More of the Same?
title_full_unstemmed Current State of Type 1 Diabetes Immunotherapy: Incremental Advances, Huge Leaps, or More of the Same?
title_short Current State of Type 1 Diabetes Immunotherapy: Incremental Advances, Huge Leaps, or More of the Same?
title_sort current state of type 1 diabetes immunotherapy: incremental advances, huge leaps, or more of the same?
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139873/
https://www.ncbi.nlm.nih.gov/pubmed/21785616
http://dx.doi.org/10.1155/2011/432016
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