TGN1412

TGN1412 is a monoclonal antibody that was developed for the treatment of rheumatoid arthritis, leukemia, and autoimmune diseases. It was created by the German biotechnology company TeGenero.

History

TGN1412 was first tested in a Phase I clinical trial in March 2006 at Northwick Park Hospital in London. The trial, which was conducted by Parexel, involved six healthy volunteers who were given the drug. Within hours of receiving the drug, all six volunteers suffered from a severe inflammatory response, known as a cytokine storm, which led to multiple organ failure. This incident, often referred to as the "Northwick Park Incident", led to a major review of the procedures used in early-stage clinical trials.

Mechanism of Action

TGN1412 is a superagonist anti-CD28 monoclonal antibody. It works by binding to the CD28 receptor on T cells, a type of white blood cell that plays a key role in the immune response. This binding stimulates the T cells to proliferate and release cytokines, proteins that help to coordinate the immune response. However, in the case of TGN1412, this stimulation was excessive, leading to a cytokine storm.

Aftermath and Impact

The TGN1412 trial had a significant impact on the conduct of clinical trials, particularly those involving novel biological entities. It led to changes in the guidelines for first-in-human trials, with a greater emphasis on safety. The incident also highlighted the limitations of preclinical testing, as the severe reaction seen in the volunteers had not been predicted by the animal studies conducted prior to the trial.

See Also

• Clinical trial
• Monoclonal antibodies
• Cytokine storm
• CD28
• TeGenero
• Parexel
• Northwick Park Incident