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Comment
. 2010 Oct;161(3):509-11.
doi: 10.1111/j.1476-5381.2010.00925.x.

Primate testing of TGN1412: right target, wrong cell

Affiliations
Comment

Primate testing of TGN1412: right target, wrong cell

M Pallardy et al. Br J Pharmacol. 2010 Oct.

Abstract

The failure of toxicity studies in non-human primates to predict the cytokine release syndrome during a first-in-man study of the CD28-specific monoclonal antibody TGN1412 has remained unexplained so far. In this issue of the BJP, work from the NIBSC first identifies the effector memory subset of human T-lymphocytes as the most likely source of the pro-inflammatory cytokines released during the study, and goes on to show that in cynomolgus monkeys, this subset lacks CD28, the target molecule of TGN1412. We discuss the implications for the TGN1412 catastrophe and for preclinical evaluation of biologicals in animal models in general.

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References

    1. Duff GW. Expert Scientific Group on Phase One Clinical Trials Final Report. Norwich, UK: Stationery Office; 2006.
    1. Eastwood D, Findlay L, Poole S, Bird C, Wadhwa M, Moore M, et al. Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T-cells. Br J Pharmacol. 2010;161:512–526. - PMC - PubMed
    1. EMA, European Medicines Agency. Guideline on strategies to identify and mitigate risks for first-in human clinical trials with investigational medicinal products. 2007. - PMC - PubMed
    1. Gogishvili T, Langenhorst D, Luhder F, Elias F, Elflein K, Dennehy KM, et al. Rapid regulatory T-cell response prevents cytokine storm in CD28 superagonist treated mice. Plos ONE. 2009;4:e4643. - PMC - PubMed
    1. Hanke T. Lessons from TGN1412. Lancet. 2006;368:1569–1570. author reply 1570. - PubMed