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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Wiley
2011-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2011/432016 |
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| author | Brett Phillips Massimo Trucco Nick Giannoukakis |
| author_facet | Brett Phillips Massimo Trucco Nick Giannoukakis |
| author_sort | Brett Phillips |
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| 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 | Article |
| id | doaj-art-72ac3c0ee93e4674ab12c17fd8b11e7d |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
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| series | Clinical and Developmental Immunology |
| spelling | doaj-art-72ac3c0ee93e4674ab12c17fd8b11e7d2025-02-03T06:44:38ZengWileyClinical and Developmental Immunology1740-25221740-25302011-01-01201110.1155/2011/432016432016Current State of Type 1 Diabetes Immunotherapy: Incremental Advances, Huge Leaps, or More of the Same?Brett Phillips0Massimo Trucco1Nick Giannoukakis2Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USADivision of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USADivision of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USAThus 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.http://dx.doi.org/10.1155/2011/432016 |
| spellingShingle | Brett Phillips Massimo Trucco Nick Giannoukakis Current State of Type 1 Diabetes Immunotherapy: Incremental Advances, Huge Leaps, or More of the Same? Clinical and Developmental Immunology |
| 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 |
| url | http://dx.doi.org/10.1155/2011/432016 |
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