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The rise and fall of the CD 28 superagonist TGN 1412 and its return as TAB 08: a personal account
Author(s) -
Hünig Thomas
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13754
Subject(s) - cytokine , cd28 , monoclonal antibody , cytokine release syndrome , medicine , inflammation , immunology , pharmacology , antibody , t cell , immune system , chimeric antigen receptor
Two decades ago, we discovered ‘superagonistic’ monoclonal antibodies specific for the CD 28 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 CD 28 superagonist TGN 1412 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 TAB 08. Here, I recount the story of CD 28 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.