Restoring the balance: immunotherapeutic combinations for autoimmune disease
Autoimmunity occurs when T cells, B cells or both are inappropriately activated, resulting in damage to one or more organ systems. Normally, high-affinity self-reactive T and B cells are eliminated in the thymus and bone marrow through a process known as central immune tolerance. However, low-affini...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2014-05-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/7/5/503 |
| _version_ | 1828386672118595584 |
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| author | Dawn E. Smilek Mario R. Ehlers Gerald T. Nepom |
| author_facet | Dawn E. Smilek Mario R. Ehlers Gerald T. Nepom |
| author_sort | Dawn E. Smilek |
| collection | DOAJ |
| description | Autoimmunity occurs when T cells, B cells or both are inappropriately activated, resulting in damage to one or more organ systems. Normally, high-affinity self-reactive T and B cells are eliminated in the thymus and bone marrow through a process known as central immune tolerance. However, low-affinity self-reactive T and B cells escape central tolerance and enter the blood and tissues, where they are kept in check by complex and non-redundant peripheral tolerance mechanisms. Dysfunction or imbalance of the immune system can lead to autoimmunity, and thus elucidation of normal tolerance mechanisms has led to identification of therapeutic targets for treating autoimmune disease. In the past 15 years, a number of disease-modifying monoclonal antibodies and genetically engineered biologic agents targeting the immune system have been approved, notably for the treatment of rheumatoid arthritis, inflammatory bowel disease and psoriasis. Although these agents represent a major advance, effective therapy for other autoimmune conditions, such as type 1 diabetes, remain elusive and will likely require intervention aimed at multiple components of the immune system. To this end, approaches that manipulate cells ex vivo and harness their complex behaviors are being tested in preclinical and clinical settings. In addition, approved biologic agents are being examined in combination with one another and with cell-based therapies. Substantial development and regulatory hurdles must be overcome in order to successfully combine immunotherapeutic biologic agents. Nevertheless, such combinations might ultimately be necessary to control autoimmune disease manifestations and restore the tolerant state. |
| first_indexed | 2024-12-10T05:41:07Z |
| format | Article |
| id | doaj.art-60f76fc4e134409499dc06bf2e8f7017 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-10T05:41:07Z |
| publishDate | 2014-05-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-60f76fc4e134409499dc06bf2e8f70172022-12-22T02:00:17ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112014-05-017550351310.1242/dmm.015099015099Restoring the balance: immunotherapeutic combinations for autoimmune diseaseDawn E. SmilekMario R. EhlersGerald T. NepomAutoimmunity occurs when T cells, B cells or both are inappropriately activated, resulting in damage to one or more organ systems. Normally, high-affinity self-reactive T and B cells are eliminated in the thymus and bone marrow through a process known as central immune tolerance. However, low-affinity self-reactive T and B cells escape central tolerance and enter the blood and tissues, where they are kept in check by complex and non-redundant peripheral tolerance mechanisms. Dysfunction or imbalance of the immune system can lead to autoimmunity, and thus elucidation of normal tolerance mechanisms has led to identification of therapeutic targets for treating autoimmune disease. In the past 15 years, a number of disease-modifying monoclonal antibodies and genetically engineered biologic agents targeting the immune system have been approved, notably for the treatment of rheumatoid arthritis, inflammatory bowel disease and psoriasis. Although these agents represent a major advance, effective therapy for other autoimmune conditions, such as type 1 diabetes, remain elusive and will likely require intervention aimed at multiple components of the immune system. To this end, approaches that manipulate cells ex vivo and harness their complex behaviors are being tested in preclinical and clinical settings. In addition, approved biologic agents are being examined in combination with one another and with cell-based therapies. Substantial development and regulatory hurdles must be overcome in order to successfully combine immunotherapeutic biologic agents. Nevertheless, such combinations might ultimately be necessary to control autoimmune disease manifestations and restore the tolerant state.http://dmm.biologists.org/content/7/5/503ToleranceAutoimmuneBiologic |
| spellingShingle | Dawn E. Smilek Mario R. Ehlers Gerald T. Nepom Restoring the balance: immunotherapeutic combinations for autoimmune disease Disease Models & Mechanisms Tolerance Autoimmune Biologic |
| title | Restoring the balance: immunotherapeutic combinations for autoimmune disease |
| title_full | Restoring the balance: immunotherapeutic combinations for autoimmune disease |
| title_fullStr | Restoring the balance: immunotherapeutic combinations for autoimmune disease |
| title_full_unstemmed | Restoring the balance: immunotherapeutic combinations for autoimmune disease |
| title_short | Restoring the balance: immunotherapeutic combinations for autoimmune disease |
| title_sort | restoring the balance immunotherapeutic combinations for autoimmune disease |
| topic | Tolerance Autoimmune Biologic |
| url | http://dmm.biologists.org/content/7/5/503 |
| work_keys_str_mv | AT dawnesmilek restoringthebalanceimmunotherapeuticcombinationsforautoimmunedisease AT mariorehlers restoringthebalanceimmunotherapeuticcombinationsforautoimmunedisease AT geraldtnepom restoringthebalanceimmunotherapeuticcombinationsforautoimmunedisease |