Article Text
Abstract
This paper reviews the existing evidence regarding the use of superagonistic anti-CD28 antibodies (CD28 superagonists) for therapeutic manipulation of regulatory T cells (Treg cells). The molecular properties of superagonistic anti-CD28 antibodies allow the generation of a strong activating signal in mature T cells, including Treg cells, without additional stimulation of the T cell receptor complex. CD28 superagonist administration in vivo leads to the preferential expansion and strong activation of naturally occurring CD4+CD25+CTLA-4+FoxP3+ Treg cells over conventional T cells. In animal models, both prophylactic and therapeutic administration of a CD28 superagonist prevented or at least greatly mitigated clinical symptoms and induced remission. Adoptive transfer experiments have further shown that CD28 superagonists mediate protection by expansion and activation of CD4+CD25+ Treg cells. Therefore, superagonistic anti-CD28 antibodies offer a promising novel treatment option for human autoimmune diseases and the first clinical trials are eagerly awaited.
- AA, adjuvant arthritis
- APC, antigen presenting cell
- EAE, experimental autoimmune encephalomyelitis
- TCR, T cell receptor
- Tconv, conventional T cell
- Treg, regulatory T cell
- anti-CD28 antibodies
- CD28 superagonists
- autoimmune diseases
- regulatory T cells
- CD4+CD25+ Treg
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Footnotes
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This work was funded by a joint grant from TeGenero ImmunoTherapeutics AG and the Bayerische Forschungsstiftung (forimmun) and by IZKF Würzburg 01 KS 903/Teilprojekt C13 (BMBF).
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Competing interests: T Kerkau and T Hünig declare a commercial interest in TeGenero ImmunoTherapeutics AG.