title: From TGN1412 to TAB08: the return of CD28 superagonist therapy to clinical development for the treatment of rheumatoid arthritis.
abstract: CD28 superagonists (CD28SA) are CD28-specific monoclonal antibodies which are able to activate T-cells without overt TCR engagement. In rodents, CD28SA efficiently activate regulatory T-cells and are therapeutically effective in multiple models of autoimmunity, inflammation and transplantation. However, a phase I study of the human CD28SA TGN1412 in 2006 resulted in a life-threatening cytokine storm. This brief review summarises preclinical work before and since the failed phase I trial with an emphasis on understanding the reasons why there had been no warning of toxicity, and how a novel assay paved the way for a new phase I, phase Ib (both completed), and an ongoing phase II study.
authors: TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
authors: Dmitry
authors: D
authors: Tyrsin
authors: TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
authors: Sergey
authors: S
authors: Chuvpilo
authors: TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
authors: Alexey
authors: A
authors: Matskevich
authors: TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
authors: Daniil
authors: D
authors: Nemenov
authors: TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
authors: Paula S
authors: PS
authors: Römer
authors: Institute for Virology and Immunobiology, University of Würzburg, Germany.
authors: Paula
authors: P
authors: Tabares
authors: Institute for Virology and Immunobiology, University of Würzburg, Germany. huenig@vim.uni-wuerzburg.de.
authors: Thomas
authors: T
authors: Hünig
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D058990:Molecular Targeted Therapy; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D018106:CD28 Antigens; D016207:Cytokines; C509303:TGN-1412