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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| 格式: | Journal article |
| 语言: | English |
| 出版: |
Frontiers Media
2018
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| _version_ | 1826293995889754112 |
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| author | Paluch, C Santos, A Anzilotti, C Cornall, R Davis, S |
| author_facet | Paluch, C Santos, A Anzilotti, C Cornall, R Davis, S |
| author_sort | Paluch, C |
| collection | OXFORD |
| 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 | 2024-03-07T03:38:48Z |
| format | Journal article |
| id | oxford-uuid:bd30473e-f983-402b-a35e-e29dba049c65 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:38:48Z |
| publishDate | 2018 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:bd30473e-f983-402b-a35e-e29dba049c652022-03-27T05:29:54ZImmune checkpoints as therapeutic targets in autoimmunityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bd30473e-f983-402b-a35e-e29dba049c65EnglishSymplectic Elements at OxfordFrontiers Media2018Paluch, CSantos, AAnzilotti, CCornall, RDavis, SAntibodies 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. |
| spellingShingle | Paluch, C Santos, A Anzilotti, C Cornall, R Davis, S Immune checkpoints as therapeutic targets in autoimmunity |
| 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 |
| work_keys_str_mv | AT paluchc immunecheckpointsastherapeutictargetsinautoimmunity AT santosa immunecheckpointsastherapeutictargetsinautoimmunity AT anzilottic immunecheckpointsastherapeutictargetsinautoimmunity AT cornallr immunecheckpointsastherapeutictargetsinautoimmunity AT daviss immunecheckpointsastherapeutictargetsinautoimmunity |