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Volume 6
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10.3390/antib6040019
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Review

Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders

by
Bernard Vanhove
1,2,3,*,
Nicolas Poirier
1,2,3,
Fadi Fakhouri
2,3,
Laetitia Laurent
2,
Bert ’t Hart
4,5,
Pedro H. Papotto
6,
Luiz V. Rizzo
7,
Masaaki Zaitsu
8,
Fadi Issa
8,
Kathryn Wood
8,
Jean-Paul Soulillou
2 and
Gilles Blancho
2,3
1
OSE Immunotherapeutics, 44200 Nantes, France
2
Centre de Recherche en Transplantation et Immunologie (CRTI) UMR1064, INSERM, Université de Nantes, 44035 Nantes, France
3
Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, 44093 Nantes, France
4
Biomedical Primate Research Centre, 2288 GJ Rijswijk, The Netherlands
5
Department Neuroscience, University of Groningen, University Medical Center, 9713 GZ Groningen, The Netherlands
6
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-004 Lisbon, Portugal
7
Hospital Israelita Albert Einstein, Av. Albert Einstein 627-701, 2-SS Bloco A, 05651-901 São Paulo, Brazil
8
Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK
*
Author to whom correspondence should be addressed.
Antibodies 2017, 6(4), 19; https://doi.org/10.3390/antib6040019
Submission received: 26 October 2017 / Revised: 16 November 2017 / Accepted: 18 November 2017 / Published: 21 November 2017
(This article belongs to the Special Issue Therapeutic Antibodies)
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Abstract

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.
Keywords: autoimmunity; T cell costimulation; antibodies autoimmunity; T cell costimulation; antibodies

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MDPI and ACS Style

Vanhove, B.; Poirier, N.; Fakhouri, F.; Laurent, L.; ’t Hart, B.; Papotto, P.H.; Rizzo, L.V.; Zaitsu, M.; Issa, F.; Wood, K.; et al. Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders. Antibodies 2017, 6, 19. https://doi.org/10.3390/antib6040019

AMA Style

Vanhove B, Poirier N, Fakhouri F, Laurent L, ’t Hart B, Papotto PH, Rizzo LV, Zaitsu M, Issa F, Wood K, et al. Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders. Antibodies. 2017; 6(4):19. https://doi.org/10.3390/antib6040019

Chicago/Turabian Style

Vanhove, Bernard, Nicolas Poirier, Fadi Fakhouri, Laetitia Laurent, Bert ’t Hart, Pedro H. Papotto, Luiz V. Rizzo, Masaaki Zaitsu, Fadi Issa, Kathryn Wood, and et al. 2017. "Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders" Antibodies 6, no. 4: 19. https://doi.org/10.3390/antib6040019

APA Style

Vanhove, B., Poirier, N., Fakhouri, F., Laurent, L., ’t Hart, B., Papotto, P. H., Rizzo, L. V., Zaitsu, M., Issa, F., Wood, K., Soulillou, J.-P., & Blancho, G. (2017). Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders. Antibodies, 6(4), 19. https://doi.org/10.3390/antib6040019

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