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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2011
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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. |
format | Online Article Text |
id | pubmed-3139873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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