Case Study:

Northwick Park

​The Northwick Park trial involved testing the experimental humanized monoclonal antibody TGN1412 targeted against CD28, a marker on effector T-cells. Administration of the antibody in humans led to binding of the human CD28 receptor on effector T-cells, resulting in cytokine release syndrome (CRS). 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 humans (Eastwood et al., 2010). This example demonstrates the need for more effective pre-clinical drug safety testing using human in vitro models.​

Alcyomics Skimune® technology could have predicted the Northwick Park drug trial disaster and 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. Alcyomics can help mitigate similar outcomes.​

Alcyomics tested an analogue of the antibody TGN1412 (kindly provided by the National Institute of Biological Standards and Control now within the MHRA*) using Skimune®. The result showed a grade III reaction with sub-epidermal damage in the skin (skin blistering) in 9/10 donors. The data showed that the assay could have predicted and prevented the Northwick Park disaster.​
TGN1412 positive Grade III response obtained using Skimune®​

A Grade III positive response was shown using the Skimune® assay to test the TGN1412 monoclonal antibody. Damage was observed at the dermal-epidermal junction (highlighted by black arrows).​

*Medicines and Healthcare products Regulatory Agency​

Case Study 2:

Alcyomics was commissioned to test 3 monoclonal antibodies in a blinded study. Antibody A and C showed a grade I negative response (intact dermal epidermal junction) and Antibody B showed a grade II positive response ( vacuolisation of keratinocytes on the dermal/epidermal junction.

Results. Antibody A was the negative control, Antibody B was a therapeutic removed from Phase I clinical trials as it caused a rash in 9 of 11 individuals and Antibody C was a modified version of Antibody B.​

How is this data useful and what value can it bring to you?​

Alcyomics Skimune® assay could have predicted the adverse effect (observed with Antibody B ) before the Phase I clinical trial allowing early identification of a problem thereby resulting in an early Go/NoGo Decision and opportunity to modify the compound.

In addition, Alcyomics also showed that the modified version of Antibody B did not cause an adverse response and was safe for Phase I clinical trials.​

Benefits of the Skimune® assay​

Detection of clinically relevant celluar immune responses
Validated against commercial available therapeutic monoclonal antibodies​
Available in combination with complementary assays
Non-animal system​
For more information on Skimune® assays and how they can help your business R&D please contact us​.
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Other application areas currently include:

Figure 1 - Histological analysis of responses to monoclonal antibodies. Antibody A & C showed a grade I (negative) response and Antibody B showed a Grade II positive response.​

Chemical Compounds

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Antibody Drug Conjugates

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Cellular Therapies

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