Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jul;2(3):332-6.
doi: 10.4103/0975-1483.66810.

TGN1412: From Discovery to Disaster

H Attarwala  1
Affiliations

TGN1412: From Discovery to Disaster

H Attarwala. J Young Pharm. 2010 Jul.

Abstract

After a drug is confirmed as safe and efficacious in preclinical studies, it is tested in healthy human volunteers for first in man trials. In 2006, a phase I clinical study was conducted for a CD28 superagonist antibody TGN1412 in six human volunteers. After very first infusion of a dose 500 times smaller than that found safe in animal studies, all six human volunteers faced life-threatening conditions involving multiorgan failure for which they were moved to intensive care unit. After this particular incident, a lot was changed over how first in man trials are approved by regulatory authorities and the way clinical trials are conducted. This review primarily deals with preclinical studies conducted by TeGenero, results of which encouraged them to test the antibody on human subjects, reasons why this drug failed in human trial and aftermath of this drug trial. In addition, another drug-Fialuridine which failed in phase 2 clinical trial leading to death of five human subjects is briefly reviewed.

Keywords: Clinical trials; Fialuridine; TGN1412.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: None declared

References

    1. Masteller EL, Warner MR, Tang Q, Tarbell KV, McDevitt H, Bluestone JA. Expansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice. J Immunol. 2005;175:3053–9. - PubMed
    1. Hunig T. Manipulation of regulatory T-cell number and function with CD28-specific monoclonal antibodies. Adv Immunol. 2007;95:111–48. - PubMed
    1. Lühder F, Huang Y, Dennehy KM, Guntermann C, Müller I, Winkler E, et al. Topological requirements and signaling properties of T cell-activating, anti-CD28 antibody superagonists. J Exp Med. 2003;197:955–66. - PMC - PubMed
    1. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006;355:1018–28. - PubMed
    1. Hanke T. Lessons from TGN1412. Lancet. 2006;368:1569–70. - PubMed