TARGET ENGAGEMENT EVALUATION
Background
Regulatory T-cells (Treg) are a key mediator of immune tolerance. Tregs are an important therapeutic target both in autoimmune disease (objective is to increase Treg activity) and in immune oncology (objective is to decrease Treg activity). A client developed a small molecule to inhibit Treg polarization which demonstrated promise in an animal model but needed to confirm efficacy in the human immune system.
Prototrial Strategy
Peripheral blood mononuclear cells were isolated from healthy volunteers and samples were enriched for naïve CD4 T-cells using magnetic bead separation. The naïve CD4 T-cells were polarized to differentiate into Tregs and the dose-dependent impact of the molecule on Treg polarization was quantified by flow cytometry.
Analytical Strategy
Outcomes
The study demonstrated the ability of the molecule to inhibit Treg polarization in a dose-dependent manner.
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