Immune Checkpoints as Therapeutic Targets in Autoimmunity
Antibodies that block the immune checkpoint receptors PD1 and CTLA4 have revolutionized the treatment of melanoma and several other cancers, but in the process, a new class of drug side effect has emerged—immune related adverse events. The observation that therapeutic blockade of these inhibitory re...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02306/full |
| _version_ | 1819209062209814528 |
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| author | Christopher Paluch Christopher Paluch Ana Mafalda Santos Ana Mafalda Santos Consuelo Anzilotti Consuelo Anzilotti Richard J. Cornall Richard J. Cornall Simon J. Davis Simon J. Davis |
| author_facet | Christopher Paluch Christopher Paluch Ana Mafalda Santos Ana Mafalda Santos Consuelo Anzilotti Consuelo Anzilotti Richard J. Cornall Richard J. Cornall Simon J. Davis Simon J. Davis |
| author_sort | Christopher Paluch |
| collection | DOAJ |
| description | Antibodies that block the immune checkpoint receptors PD1 and CTLA4 have revolutionized the treatment of melanoma and several other cancers, but in the process, a new class of drug side effect has emerged—immune related adverse events. The observation that therapeutic blockade of these inhibitory receptors is sufficient to break self-tolerance, highlights their crucial role in the physiological modulation of immune responses. Here, we discuss the rationale for targeting immune checkpoint receptors with agonistic agents in autoimmunity, to restore tolerance when it is lost. We review progress that has been made to date, using Fc-fusion proteins, monoclonal antibodies or other novel constructs to induce immunosuppressive signaling through these pathways. Finally, we explore potential mechanisms by which these receptors trigger and modulate immune cell function, and how understanding these processes might shape the design of more effective therapeutic agents in future. |
| first_indexed | 2024-12-23T05:49:18Z |
| format | Article |
| id | doaj.art-673980b531654510a0d8ba4795ba7cb5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T05:49:18Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-673980b531654510a0d8ba4795ba7cb52022-12-21T17:58:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02306406796Immune Checkpoints as Therapeutic Targets in AutoimmunityChristopher Paluch0Christopher Paluch1Ana Mafalda Santos2Ana Mafalda Santos3Consuelo Anzilotti4Consuelo Anzilotti5Richard J. Cornall6Richard J. Cornall7Simon J. Davis8Simon J. Davis9MRC Human Immunology Unit, University of Oxford, Oxford, United KingdomNuffield Department of Clinical Medicine, University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, University of Oxford, Oxford, United KingdomRadcliffe Department of Medicine, University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, University of Oxford, Oxford, United KingdomRadcliffe Department of Medicine, University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, University of Oxford, Oxford, United KingdomNuffield Department of Clinical Medicine, University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, University of Oxford, Oxford, United KingdomRadcliffe Department of Medicine, University of Oxford, Oxford, United KingdomAntibodies that block the immune checkpoint receptors PD1 and CTLA4 have revolutionized the treatment of melanoma and several other cancers, but in the process, a new class of drug side effect has emerged—immune related adverse events. The observation that therapeutic blockade of these inhibitory receptors is sufficient to break self-tolerance, highlights their crucial role in the physiological modulation of immune responses. Here, we discuss the rationale for targeting immune checkpoint receptors with agonistic agents in autoimmunity, to restore tolerance when it is lost. We review progress that has been made to date, using Fc-fusion proteins, monoclonal antibodies or other novel constructs to induce immunosuppressive signaling through these pathways. Finally, we explore potential mechanisms by which these receptors trigger and modulate immune cell function, and how understanding these processes might shape the design of more effective therapeutic agents in future.https://www.frontiersin.org/article/10.3389/fimmu.2018.02306/fullimmune checkpointinhibitory receptoragonistantibodyautoimmunityimmunosuppression |
| spellingShingle | Christopher Paluch Christopher Paluch Ana Mafalda Santos Ana Mafalda Santos Consuelo Anzilotti Consuelo Anzilotti Richard J. Cornall Richard J. Cornall Simon J. Davis Simon J. Davis Immune Checkpoints as Therapeutic Targets in Autoimmunity Frontiers in Immunology immune checkpoint inhibitory receptor agonist antibody autoimmunity immunosuppression |
| title | Immune Checkpoints as Therapeutic Targets in Autoimmunity |
| title_full | Immune Checkpoints as Therapeutic Targets in Autoimmunity |
| title_fullStr | Immune Checkpoints as Therapeutic Targets in Autoimmunity |
| title_full_unstemmed | Immune Checkpoints as Therapeutic Targets in Autoimmunity |
| title_short | Immune Checkpoints as Therapeutic Targets in Autoimmunity |
| title_sort | immune checkpoints as therapeutic targets in autoimmunity |
| topic | immune checkpoint inhibitory receptor agonist antibody autoimmunity immunosuppression |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02306/full |
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