TGN1412
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized (from mouse) |
| Target | CD28 |
| Clinical data | |
| Routes of administration |
intravenous |
| ATC code |
|
| Legal status | |
| Legal status |
|
TGN1412 (also known as CD28-SuperMAB and TAB08) was the working name of an immunomodulatory drug developed by Thomas Hünig, professor at the University of Würzburg.
It was withdrawn from development after inducing severe inflammatory reactions in the first-in-man study by PAREXEL in London in March 2006. The developing company, TeGenero Immuno Therapeutics, went bankrupt later that year.
The commercial rights were then acquired by a Russian investor. The drug was renamed TAB08. The Russian biotechnology company TheraMAB conducted Phase I trials with a much lower dose (0.1%) of the antibody than was used in the London study, and they had planned to initiate Phase II trials in June 2015.
Originally intended for the treatment of B cell chronic lymphocytic leukemia (B-CLL) and rheumatoid arthritis, TGN1412 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. CD28 is the co-receptor for the T cell receptor; It binds to receptors on the interacting partner in the reaction through one of its ligands (B7 family).
In its first human clinical trials, it caused catastrophic systemic organ failures 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. 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.
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