Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders
The effector functions of T lymphocytes are responsible for most autoimmune disorders and act by directly damaging tissues or by indirectly promoting inflammation and antibody responses. Co-stimulatory and co-inhibitory T cell receptor molecules are the primary pharmacological targets that enable in...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-11-01
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| Series: | Antibodies |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4468/6/4/19 |
| _version_ | 1828849567474384896 |
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| author | Bernard Vanhove Nicolas Poirier Fadi Fakhouri Laetitia Laurent Bert ’t Hart Pedro H. Papotto Luiz V. Rizzo Masaaki Zaitsu Fadi Issa Kathryn Wood Jean-Paul Soulillou Gilles Blancho |
| author_facet | Bernard Vanhove Nicolas Poirier Fadi Fakhouri Laetitia Laurent Bert ’t Hart Pedro H. Papotto Luiz V. Rizzo Masaaki Zaitsu Fadi Issa Kathryn Wood Jean-Paul Soulillou Gilles Blancho |
| author_sort | Bernard Vanhove |
| collection | DOAJ |
| description | The effector functions of T lymphocytes are responsible for most autoimmune disorders and act by directly damaging tissues or by indirectly promoting inflammation and antibody responses. Co-stimulatory and co-inhibitory T cell receptor molecules are the primary pharmacological targets that enable interference with immune-mediated diseases. Among these, selective CD28 antagonists have drawn special interest, since they tip the co-stimulation/co-inhibition balance towards efficiently inhibiting effector T cells while promoting suppression by pre-existing regulatory T-cells. After having demonstrated outstanding therapeutic efficacy in multiple models of autoimmunity, inflammation and transplantation, and safety in phase-I studies in humans, selective CD28 antagonists are currently in early clinical development for the treatment of systemic lupus erythematous and rheumatoid arthritis. Here, we review the available proof of concept studies for CD28 antagonists in autoimmunity, with a special focus on the mechanisms of action. |
| first_indexed | 2024-12-12T22:53:28Z |
| format | Article |
| id | doaj.art-5af90d7986b94022a85e7e1b6b33d2be |
| institution | Directory Open Access Journal |
| issn | 2073-4468 |
| language | English |
| last_indexed | 2024-12-12T22:53:28Z |
| publishDate | 2017-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj.art-5af90d7986b94022a85e7e1b6b33d2be2022-12-22T00:09:00ZengMDPI AGAntibodies2073-44682017-11-01641910.3390/antib6040019antib6040019Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune DisordersBernard Vanhove0Nicolas Poirier1Fadi Fakhouri2Laetitia Laurent3Bert ’t Hart4Pedro H. Papotto5Luiz V. Rizzo6Masaaki Zaitsu7Fadi Issa8Kathryn Wood9Jean-Paul Soulillou10Gilles Blancho11OSE Immunotherapeutics, 44200 Nantes, FranceOSE Immunotherapeutics, 44200 Nantes, FranceCentre de Recherche en Transplantation et Immunologie (CRTI) UMR1064, INSERM, Université de Nantes, 44035 Nantes, FranceCentre de Recherche en Transplantation et Immunologie (CRTI) UMR1064, INSERM, Université de Nantes, 44035 Nantes, FranceBiomedical Primate Research Centre, 2288 GJ Rijswijk, The NetherlandsInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-004 Lisbon, PortugalHospital Israelita Albert Einstein, Av. Albert Einstein 627-701, 2-SS Bloco A, 05651-901 São Paulo, BrazilNuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UKNuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UKNuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UKCentre de Recherche en Transplantation et Immunologie (CRTI) UMR1064, INSERM, Université de Nantes, 44035 Nantes, FranceCentre de Recherche en Transplantation et Immunologie (CRTI) UMR1064, INSERM, Université de Nantes, 44035 Nantes, FranceThe effector functions of T lymphocytes are responsible for most autoimmune disorders and act by directly damaging tissues or by indirectly promoting inflammation and antibody responses. Co-stimulatory and co-inhibitory T cell receptor molecules are the primary pharmacological targets that enable interference with immune-mediated diseases. Among these, selective CD28 antagonists have drawn special interest, since they tip the co-stimulation/co-inhibition balance towards efficiently inhibiting effector T cells while promoting suppression by pre-existing regulatory T-cells. After having demonstrated outstanding therapeutic efficacy in multiple models of autoimmunity, inflammation and transplantation, and safety in phase-I studies in humans, selective CD28 antagonists are currently in early clinical development for the treatment of systemic lupus erythematous and rheumatoid arthritis. Here, we review the available proof of concept studies for CD28 antagonists in autoimmunity, with a special focus on the mechanisms of action.https://www.mdpi.com/2073-4468/6/4/19autoimmunityT cell costimulationantibodies |
| spellingShingle | Bernard Vanhove Nicolas Poirier Fadi Fakhouri Laetitia Laurent Bert ’t Hart Pedro H. Papotto Luiz V. Rizzo Masaaki Zaitsu Fadi Issa Kathryn Wood Jean-Paul Soulillou Gilles Blancho Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders Antibodies autoimmunity T cell costimulation antibodies |
| title | Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders |
| title_full | Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders |
| title_fullStr | Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders |
| title_full_unstemmed | Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders |
| title_short | Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders |
| title_sort | antagonist anti cd28 therapeutics for the treatment of autoimmune disorders |
| topic | autoimmunity T cell costimulation antibodies |
| url | https://www.mdpi.com/2073-4468/6/4/19 |
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