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


1, 2, 3, 4, 5, 6, 7

 

  1. TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
  2. TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
  3. TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
  4. TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
  5. TheraMAB LLC, Würzburg, Germany, and Moscow, Russia.
  6. Institute for Virology and Immunobiology, University of Würzburg, Germany.
  7. 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.

Rheumatology Article