The calm after the cytokine storm: lessons from the TGN1412 trial.

Published

Journal Article

In March 2006, a phase I study of the superagonistic anti-CD28 antibody TGN1412 caused a massive cytokine storm and multiorgan failure in six healthy human volunteers. Such a profound impact on the immune system was not predicted by preclinical animal studies. In a study from this issue of the JCI, Müller et al. treated rats with the superagonistic anti-CD28 antibody JJ316 and found that it rapidly induced a marked T cell lymphopenia by trapping T cells in the spleen and lymph nodes (see the related article beginning on page 1405). This dramatic redistribution of T cells simulated the profound T cell lymphopenia observed in human recipients of TGN1412. In contrast, JJ316 treatment in the rats did not reproduce the massive cytokine storm observed following TGN1412 administration to the human volunteers. These results point to similarities as well as differences between rodents and humans in the immunological effects of superagonistic anti-CD28 antibody treatment and raise further questions about how best to design preclinical studies that can better predict the risks of novel immunotherapeutics in humans.

Full Text

Duke Authors

Cited Authors

  • St Clair, EW

Published Date

  • April 2008

Published In

Volume / Issue

  • 118 / 4

Start / End Page

  • 1344 - 1347

PubMed ID

  • 18357347

Pubmed Central ID

  • 18357347

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI35382

Language

  • eng

Conference Location

  • United States