Theralizumab

Theralizumab (also known as TGN1412) is a monoclonal antibody originally developed for the treatment of B cell chronic lymphocytic leukemia (B-CLL), autoimmune diseases, and inflammation. It was developed by the German biotechnology company TeGenero Immuno Therapeutics.

History

Theralizumab was first tested in a Phase I clinical trial in March 2006 at Northwick Park Hospital in London, under the supervision of Parexel, a contract research organization. The trial resulted in a serious adverse event, causing all six healthy volunteers to be hospitalized with a systemic inflammatory response syndrome (SIRS), also known as a "cytokine storm". This event led to a major review of clinical trial procedures in the UK and worldwide.

Mechanism of Action

Theralizumab is a superagonist antibody that targets the CD28 molecule on the surface of T cells. Unlike conventional CD28-targeting antibodies, Theralizumab can activate T cells without the need for a secondary signal from antigen-presenting cells. This property allows it to stimulate a strong immune response, which can be beneficial in treating diseases where the immune system is underactive. However, this also increases the risk of overstimulating the immune system, leading to a cytokine storm.

Clinical Trials and Controversy

The Phase I clinical trial of Theralizumab is infamous for the severe adverse reactions experienced by the volunteers. The trial was conducted on six healthy male volunteers, who were administered the drug intravenously. Within hours, all six volunteers developed symptoms of a cytokine storm, including high fever, swelling, and organ failure. This event, often referred to as the "Northwick Park Incident", led to a major review of clinical trial procedures in the UK and worldwide.

Despite the serious adverse events in the Phase I trial, research on Theralizumab has continued, with modifications to the dosing regimen and patient population. It is currently being investigated for potential use in treating autoimmune diseases and certain types of cancer.

See Also

• Monoclonal antibodies
• Clinical trial
• Cytokine storm
• Autoimmune disease
• B cell chronic lymphocytic leukemia