Ex vivo blood stimulation allows us to ‘see’ immunological biomarkers of drug-effect in healthy volunteers.
Phase I clinical research organisations are ideally placed to take advantage of the close proximity from the bedside to the bench, allowing whole blood samples to be collected and analysed without the risk of sample degradation during transit. But what if the IMP in question is designed to interact with the immune system? Most phase I clinical studies are performed using normal, healthy volunteers in order to evaluate drug safety, tolerability and ADME (absorption, distribution, metabolism and excretion) characteristics. How can immunological biomarkers of drug-effect be measured where the trial subjects display only basal levels of immune system activation?
Blood samples taken from normal volunteers are stimulated in the laboratory to activate the immune system. Ex vivo blood stimulation studies therefore allow the evaluation of the effect of a new compound in a ‘living system’ in which the immune system has been challenged. Biomarkers can then be measured by traditional techniques, such as: enzyme linked assays (EIAs); more specialised techniques such as flow cytometry, which allow functional evaluation of living cell populations; and multiplex analysis of intracellular and extra-cellular mediators.
Ex vivo blood stimulation can be used to evaluate the mechanism of action, efficacy and safety of novel compounds at the earliest possible stage in drug development, increasing confidence in go/no-go decision making.
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