Case Study 1
If the Alcyomics Skimune® technology had been available the Northwick Park drug trial disaster, which resulted in catastrophic systemic organ failure in human subjects, could have been averted. Most of us remember vividly the drug trial conducted at the Northwick Park Hospital in London. This was an extreme example of what can go wrong when drugs are introduced to patients without the correct testing protocols.
The trial involved the experimental monoclonal antibody TGN1412 which was a monoclonal antibody targetted towards CD28, a marker found on regulatory (CD4+ CD28+) T cells.
The antibody had been tested vigorously in pre-clinical trials using Cynomolgouse and Rhesus monkeys. However, the testing in monkeys was inappropriate due to the CD28+ cells in the animals not expressing the proinflammatory cytokines like the human counterpart (Eastwood et al 2010). Following administration of the antibody in humans, it bound to CD28 present on T cells and resulted in mass cytokine release, also known as cytokine release syndrome (CRS).
This extreme example demonstrates the need for more effective drug testing and human in vitro models. This is especially true when one considers the increasing number of biological drugs (e.g. monoclonal antibodies, biosimilars and cellular therapies) planned or in development.
The antibody is of course no longer on the market but Alcyomics has signed a Material Transfer Agreement with NIBSC (The National Institute for Biological Standards and Control) and is testing their analogue of the antibody, raised for in vitro testing, in order to alleviate this type of problem in the future. Alcyomics is now working with NIBSC as a partner supported by a TSB grant in the development of a prototype to further develop the assays in this regard.
Alcyomics has tested the anti-CD28 antibody in the human in vitro skin explant assay Skimune®Mab. The result shows a grade III reaction with sub-epidermal damage in the skin (skin blistering). The data shows that the assay could have predicted and prevented the Northwick Park disaster.