Therapy
From TGN1412 to TAB08: the return of CD28 superagonist therapy to clinical development for the treatment of rheumatoid arthritis
D. Tyrsin1, S. Chuvpilo2, A. Matskevich3, D. Nemenov4, P.S. Römer5, P. Tabares6, T. Hünig7
- TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
- TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
- TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
- TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
- TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
- Institute for Virology and Immunobiology, University of Würzburg, Germany.
- Institute for Virology and Immunobiology, University of Würzburg, Germany. huenig@vim.uni-wuerzburg.de
CER9713
2016 Vol.34, N°4 ,Suppl.98
PI 0045, PF 0048
Therapy
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PMID: 27586803 [PubMed]
Received: 30/06/2016
Accepted : 30/06/2016
In Press: 20/07/2016
Published: 03/08/2016
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.
