From TGN1412 to TAB08: the return of CD28 superagonist therapy to clinical development for the treatment of rheumatoid arthritis

  • Clin Exp Rheumatol. 2016 Jul-Aug;34(4 Suppl 98):45-8.
Dmitry Tyrsin  1 ,  Sergey Chuvpilo  1 ,  Alexey Matskevich  1 ,  Daniil Nemenov  1 ,  Paula S Römer  1 ,  Paula Tabares  2 ,  Thomas Hünig  3
Affiliations
  • 1. TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
  • 2. Institute for Virology and Immunobiology, University of Würzburg, Germany.
  • 3. Institute for Virology and Immunobiology, University of Würzburg, Germany. [email protected].
PMID: 27586803
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.

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