Superagonistic anti-CD28 antibodies: potent activators of regulatory T cells for the therapy of autoimmune diseases.
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.
Beyersdorf
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N
Institute for Virology and Immunobiology, University of Würzburg, Versbacherstr. 7, 97078 Würzburg, Germany.
Hanke
T
T
Kerkau
T
T
Hünig
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D018106:CD28 Antigens / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D007376:Interleukin-2