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FEBS J. 2016 Sep;283(18):3325-34. doi: 10.1111/febs.13754. Epub 2016 Jun 6.

The rise and fall of the CD28 superagonist TGN1412 and its return as TAB08: a personal account.

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Institute for Virology and Immunobiology, University of Würzburg, Germany.


Two decades ago, we discovered 'superagonistic' monoclonal antibodies specific for the CD28 molecule which are able to polyclonally activate T cells, in particular regulatory T cells, and are therapeutically active in many rodent models of autoimmunity, inflammation, transplantation, and tissue repair. A phase I trial of the human CD28 superagonist TGN1412 failed in 2006 due to an unexpected cytokine release syndrome, but after it became clear that dose-reduction allows to preferentially address regulatory T cells also in humans, clinical development was resumed under the name TAB08. Here, I recount the story of CD28 superagonist development from a personal perspective with an emphasis on the dramatic events during and after the 2006 phase I trial, the reasons for the failure of preclinical research to warn of the impending cytokine storm, and on the research which allowed resumption of clinical development.


CD28 superagonist; TAB08; TGN1412; cytokine storm; regulatory T cell; therapeutic monoclonal antibody

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