Case Study 1
If the Alcyomics Skimune® technology had been available the Northwick Park drug trial disaster in 2006, which resulted in catastrophic systemic organ failure in human subjects, could have been averted. 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 humanized monoclonal antibody TGN1412 targeted against CD28, a marker on effector T cells.
Pre-clinical tests using Cynomolgus monkeys were unable to detect the immunotoxicity of TGN1412 due to the difference in receptor expression of CD28 on CD4+ memory T cells in this species compared to the humans (Eastwood et al., 2010). Administration of the antibody in humans therefore led to binding of the human CD28 receptor on effector T cells, resulting in cytokine release syndrome (CRS).
This extreme example demonstrates the need for more effective pre-clinical drug safety testing using human in vitro models.
Alcyomics tested an analogue of the antibody TGN1412 (kindly provided by the National Institute of Biological Standards and Control) using Skimune®Mab. The result showed a grade III reaction with sub-epidermal damage in the skin (skin blistering). The data showed that the assay could have predicted and prevented the Northwick Park disaster.
Figure 1: TGN1412 positive Grade III response obtained from Skimune®Mab
A Grade III positive response was shown using Skimune®Mab assay to test the TGN1412 monoclonal antibody. Positive response indicated by damage between the dermal-epidermal junction (highlighted by black arrows).