Ann Rheum Dis. 2005 Nov;64 Suppl 4:iv91-5.

Superagonistic anti-CD28 antibodies: potent activators of regulatory T cells for the therapy of autoimmune diseases.

Beyersdorf N, Hanke T, Kerkau T, Hünig T.

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Institute for Virology and Immunobiology, University of Würzburg, Versbacherstr. 7, 97078 Würzburg, Germany.

Abstract

This paper reviews the existing evidence regarding the use of superagonistic anti-CD28 antibodies (CD28 superagonists) for therapeutic manipulation of regulatory T cells (T(reg) cells). The molecular properties of superagonistic anti-CD28 antibodies allow the generation of a strong activating signal in mature T cells, including T(reg) 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+ T(reg) 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+ T(reg) cells. Therefore, superagonistic anti-CD28 antibodies offer a promising novel treatment option for human autoimmune diseases and the first clinical trials are eagerly awaited.

PMID:: 16239397; [PubMed - indexed for MEDLINE]
PMCID:: PMC1766908

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