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The storm has cleared: lessons from the CD28 superagonist TGN1412 trial

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The life-threatening cytokine-release syndrome suffered by six volunteers in a Phase I clinical trial following administration of the CD28 superagonist antibody TGN1412 (developed by TeGenero) in March 2006 was completely unpredicted by the preclinical studies. Here, Thomas Hünig, main founder of TeGenero, describes the recent investigations into what went wrong and discusses the lessons learnt for future clinical trials.

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Change history

  • 18 April 2012

    Part of a sentence on page two was missing from the version of this article originally published online. The corrected sentence now reads: "By contrast, the therapeutic monoclonal antibody OKT3, which is specific for the TCR component CD3 and has been in clinical use for decades to treat transplant rejection, induces cytokine production from PBMCs and is a notorious CRS inducer." Nature Reviews Immunology apologises for this error. In addition, reference 7 was incorrect. This has been corrected to: "Gogishvili, T. et al. Rapid regulatory T-cell response prevents cytokine storm in CD28 superagonist treated mice. PLoS ONE 4, e4643 (2009)." The author apologizes for this error.


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Thanks go to my dedicated laboratory team, in particular P. Römer and S. Berr, and to TheraMAB for providing TGN1412. The author is supported by the Deutsche Forschungsgemeinschaft through CRC52.

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Thomas Hünig is a consultant for TheraMAB LLC, which owns a patent application for the 'resTore' culture system and the rights to TGN1412.

Supplementary information

Supplementary information S1 (figure)

Differential response to TGN1412 due to tonic T cell receptor signalling. (PDF 394 kb)

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Hünig, T. The storm has cleared: lessons from the CD28 superagonist TGN1412 trial. Nat Rev Immunol 12, 317–318 (2012).

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