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

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.

• Authors: N Beyersdorf, T Hanke, T Kerkau, T Hünig
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 64 Suppl 4 Pg. iv91-5 (Nov 2005) ISSN: 0003-4967 [Print] England
• PMID: 16239397 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antibodies, Monoclonal
• CD28 Antigens
• Interleukin-2

Topics

• Animals
• Antibodies, Monoclonal (immunology, therapeutic use)
• Autoimmune Diseases (immunology, therapy)
• CD28 Antigens (immunology)
• Humans
• Interleukin-2 (immunology)
• Lymphocyte Activation (immunology)
• Rats
• T-Lymphocytes, Regulatory (immunology)