Rheumatoid Arthritis Support

TGN1412 (also known as CD28-SuperMAB) is the working name of an immunomodulatory drug which was withdrawn from development.

Originally intended for the treatment of B cell chronic lymphocytic leukemia (B-CLL) and rheumatoid arthritis, it is a humanised monoclonal antibody that not only binds to, but is a strong agonist for, the CD28 receptor of the immune system's T cells.

In its first human clinical trials in March 2006, it caused catastrophic systemic organ failure in the subjects, despite being administered at a supposed sub-clinical dose of 0.1& mg per kg; some 500 times lower than the dose found safe in animals. Six volunteers were hospitalized on 13 March 2006, at least four of these suffering from multiple organ dysfunction, and one trial volunteer is said to show signs of developing cancer.{}

The developing company, TeGenero Immuno Therapeutics, entered into insolvency proceedings later in 2006. Tentative opinions from an as-yet uncompleted inquiry suggest that the problems resulted from "unforeseen biological action in humans", rather than breach of trial protocols, and the case therefore has had important ramifications for future trials of potentially powerful clinical agents.

Scientists in early 2007 put forth the theory that the drug acted in a different fashion in humans as compared with the laboratory animals in which the drug was first tried. The severe reactions in humans could have only occurred, they believe, in animals with memory B lymphocytes. Animals raised in a sterile lab would presumably have no 'memory' of previous illnesses, thus would not exhibit the severe reactions that occurred in the human subjects.

The drug, which was designated as an orphan medical product by the European Medicines Agency in March 2005, was developed by TeGenero Immuno Therapeutics, tested by Parexel and manufactured by Boehringer-Ingelheim. TeGenero announced the first elucidation of the molecular structure of CD28 almost exactly one year prior to commencement of the TGN1412 phase I clinical trial.


Adapted from the Wikipedia article TGN1412, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki